Increased non-relapse mortality in older people with allogeneic hematopoietic stem cell transplantation using fludarabine and myeloablative dose of busulfan-based regimen

Increased non-relapse mortality in older people with allogeneic hematopoietic stem cell transplantation using fludarabine and myeloablative dose of busulfan-based regimen | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Increased non-relapse mortality in older people with allogeneic hematopoietic stem cell transplantation using fludarabine and myeloablative dose of busulfan-based regimen Akihito Shinohara, Michiho Shindo, Emiko Sakaida, Naoyuki Uchida, and 14 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4227690/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Fludarabine and myeloablative doses of busulfan-based regimens (FluBu4) are used in a wide age range as a reduced toxicity conditioning regimen for allogeneic hematopoietic stem cell transplantation (HSCT). However, their tolerability in older people has not been adequately examined. This retrospective study analyzed data from Transplant Registry Unified Management Program in Japan. Patients who were >15 years old (y/o), had hematological malignancies, and received their first HSCT using FluBu4 between 2006 and 2017 were included. They were categorized into the younger group (<60 y/o, N = 1295) and the older group (≥60 y/o, N = 993). The 3-year overall survival (OS) rate after HSCT was significantly worse in the older group than in the younger group (P < 0.01, 39.9% versus 48.5%). The 3-year non-relapse mortality (NRM) was significantly higher in the older group than in the younger group (P < 0.01, 30.9% versus 23.0%), and the 3-year cumulative incidence of relapse was comparable between the groups. According to the multivariate analysis, age ≥ 60 years was significantly associated with poor OS (P < 0.01) and high NRM (P < 0.01). In subgroup analysis of the older group, the use of additional chemotherapeutic drugs to FluBu4 was significantly associated with poor OS (P = 0.01) and high NRM (P < 0.01). Total body irradiation was significantly associated with high NRM (P < 0.01) and 1-year incidence of sinusoidal obstruction syndrome (P < 0.01) but not with OS. Thus, FluBu4 should be used with caution in older people. Allogeneic hematopoietic stem cell transplantation conditioning regimen busulfan older people Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction Despite modern advances in molecular-targeted drugs, monoclonal antibody, immunotherapies, relapsed and refractory hematological malignancies remain major problems[1–6]. Allogeneic hematopoietic stem cell transplantation (HSCT) remains an important curative treatment for relapsed and refractory hematological malignancies. In the early days, HSCT using bone myeloablative conditioning regimens (MAC) such as cyclophosphamide and total body irradiation (CyTBI) or busulfan and cyclophosphamide (BuCy) has been the standard method[7–9]; however, MAC was not feasible for patients with organ damage or older people [10]. In consideration of this concern, various reduced-intensity conditioning regimens (RICs) were developed; currently, HSCT for older patients with leukemia has mainly used RIC[11]. Fludarabine and four days of busulfan (FluBu4), which consists of fludarabine combined with a myeloablative dose of busulfan, has been frequently used as a less toxic regimen than conventional MAC while maintaining antitumor effects on hematopoietic malignancies[11, 12]. FluBu4 showed an antitumor effect on myeloid tumors comparable to BuCy while reducing non-relapse mortality (NRM)[13]. Conventional MAC is indicated up to age 50–60 years[14], whereas FluBu4 has been used at older ages. However, problems potentially associated with FluBu4 in older people have not been sufficiently examined, and many issues must be considered, including the upper age limit for this therapy, whether to administer FluBu4 in addition to TBI and chemotherapy in older people, and FluBu4-associated complications such as sinusoidal obstruction syndrome (SOS) that need particular attention. Therefore, this study investigated this issue using data from the Transplant Registry Unified Management Program (TRUMP) of the Japanese Data Center for Hematopoietic Cell Transplantation[15–17] and divided patients receiving FluBu4-based regimen at HSCT into two groups by 60 years old (y/o). Methods Patients and data collection This multicenter retrospective study used data from TRUMP on behalf of the Transplant Complication Working Group of the Japanese Society for Transplantation and Cellular Therapy (JSTCT). v This study was conducted in accordance with the Declaration of Helsinki and was approved by the institutional review boards of Tokyo Women’s Medical University Hospital and the JSTCT. Patients aged >15 years with hematological malignancies, who received the first HSCT between 2006 and 2017 in Japan, were included. They all received Flu/Bu4 (total intravenous busulfan dose of 11.2–16 mg/kg or equivalent) at HSCT. Patients who received TBI, anti-thymocyte globulin (ATG), anti-lymphocyte globulin (ALG), or other chemotherapeutic drugs were also included. The patients who received allo-HSCT from cord-blood donors were excluded. Definition and statistical analysis To reflect current practice in Japan, human leukocyte antigen (HLA) matching in related donors was assessed by serological data for HLA-A, HLA-B, and HLA-DR loci. An HLA match in related donors indicates that the recipient’s antigens were identical to the donor’s antigens at 6/6 loci. In unrelated donors, it was assessed by genotyping for HLA-A, HLA-B, HLA-C, and HLA-DR loci. In unrelated donors, an HLA match indicates that the recipient’s allele was identical to the donor’s allele at 8/8 loci. Neutrophil engraftment was defined as a neutrophil count of ≥500/mm 3 of blood for 3 days. Acute and chronic graft versus host disease (GVHD) were graded by each physician in accordance with previous reports[18, 19]. The disease stage of hematological malignancies at HSCT was classified into three categories (early, intermediate, and late) in accordance with the European Group for Blood and Marrow Transplantation risk score[20]. Hematopoietic cell transplantation-specific comorbidity index (HCT-CI) and performance status (PS) at HSCT were estimated as described previously[21, 22]. SOS was diagnosed by a primary physician at each institution with reference to the Baltimore or the modified Seattle criteria[23, 24]. If the patient or the donor tested positive for anti-cytomegalovirus (CMV) antibodies at HSCT, the patient was considered at risk for CMV infection. In analyzing the cause of death, descriptions of the primary and secondary causes of death in the registry data are combined; because in some cases more than one entry was made for a single patient, no tests for significant differences were performed. Overall survival (OS) was defined as the time from the date of HSCT until death or last observation and estimated using the Kaplan–Meier method[25]. The difference in survival curves was assessed with the log-rank test. Cox proportional hazards regression model was used to identify OS-associated prognostic factors in the univariate and multivariate analyses. Factors that showed a significant effect (P < 0.05) in the univariate analysis were selected for the multivariate analysis. NRM was defined as death without relapse after allo-HSCT. NRM and cumulative incidence of relapse (CIR), neutrophil engraftment, acute GVHD, chronic GVHD, and SOS were assessed with Gray’s method[26]. In the NRM and CIR analysis, the other was assumed as a competing event. In the analysis of the cumulative incidence of acute GVHD (grades II–IV and grades III–IV), chronic GVHD (all grades and extensive), neutrophil engraftment, and SOS, death from any cause was assumed as a competing event. Fine and Gray proportional hazards regression model was used to identify prognostic factors associated with NRM and CIR in the univariate and multivariate analyses[27]. In the multivariate analysis of NRM and CIR, the factors selected were those that showed a significant effect (P < 0.05) in the univariate analysis. Categorical and continuous variables were compared using chi-squared tests and Student’s t-tests (two-sided), respectively. P values <0.05 were considered statistically significant. The dataset for this study was edited using STATA version 16.1 (StataCorp LLC, TX, USA), and statistical analyses were performed using EZR (Saitama Medical Center, Jichi Medical University, Saitama, Japan; http://www.jichi.ac.jp/saitama-sct/SaitamaHP.files/statmedEN.html), which is a graphical user interface for R (The R Foundation for Statistical Computing, Vienna, Austria, version 4.0.3)[28]. Results Characteristics of the patients who received HSCT using FluBu4 The median follow-up of survivors was 30.5 (range 15–4109) months. Patients’ background according to their age groups (younger group, <60 y/o; older group, ≥60 y/o) are shown in Table 1. The median age of the patients was 58 (range 16–80) years, and 43.4% of the patients were ≥60 y/o. Of the 2,288 patients, 62.6% were male. Patients were diagnosed with myeloid (87.1%), lymphoid (9.1%), and other (3.0%) malignancies. Approximately two-thirds of the patients (66.4%) received bone marrow transplantation, and 584 (25.5%) and 830 (36.3%) received HSCT from matched-related donors and 8/8 matched-unrelated donors. Although this study allowed the use of intravenous busulfan up to a total dose of 16 mg/kg, 2244 (98.1%) actually analyzed used busulfan at a total dose of 12.8 mg/kg or less. Dose adjustment of busulfan by therapeutic dose monitoring (TDM) in adult HSCT is not commonly performed in Japan, and there were no data on this practice in this dataset. The median day of neutrophil engraftment was day 16 in both groups. The cumulative incidence of neutrophil engraftment at day 100 was 96.3% (95% confidence interval [CI]; 95.1%–97.2%) in the younger group and 95.5% (95% CI 94.0%–96.6%) in the older group (P = 0.053). In addition, no significant difference was found in the case of secondary graft failure in both groups (P = 0.38). Survival analysis (OS, NRM, and CIR) according to age groups The 3-year OS after HSCT in the older group was significantly worse than that in the younger group (39.9% [95% CI 36.5%–43.2%] versus 48.5% [95% CI 45.4%–51.4%], P < 0.01, Figure 1). While the 3-year NRM in the older group was significantly higher than for the younger group (30.9% [95% CI 27.9%–34.0%] versus 23.0% [95% CI 20.6%–25.5%], P < 0.01, Figure 2a), and the 3-year CIR was comparable between the two groups (32.1% [95% CI 29.1%–35.1%] versus 32.1% [95% CI 29.4%–35.7%], P = 0.67, Figure 2b). In addition, the 3-year NRM for patients aged >65 years was 35.7% (95% CI 29.7%–42.2%), and for patients aged 60–65 years, excluding this high-risk patient group from the older group, the 3-year NRM was 29.4% (95% CI 26.0%–33.0%). This worsening of NRM in patients aged 60–65 years was significantly different from that in the younger group (P < 0.01). The OS was significantly worse in the 60–65 age group than that in the younger group (P < 0.01, Supplemental Figures 1a and 1b) because of this change in NRM as CIR was comparable in these three groups (Supplemental Figure 1c). According to the multivariate analysis, increased patient age (≥60 years), hematological diseases other than myeloid tumors, time from diagnosis to HSCT (<1 year), advanced disease stage at HSCT (late), HLA-mismatched donor, sex combination (HSCT from female donor to male recipient), poor PS (2–4), and high HCT-CI score (≥3) were significantly associated with an increased risk of poor OS (Table 2A). The univariate analysis for OS is shown in Supplemental Table 1A. Regarding NRM, the results of the univariate and multivariate analyses are shown in Supplemental Table 2B and Table 2B. Increased patient age (≥60 years), hematological diseases other than myeloid tumors, HLA-mismatched donor, and poor PS were identified as significant factors for poor NRM, which were the common prognostic factors found in the OS analysis. Regarding CIR, the results of the univariate and multivariate analyses are shown in Supplemental Table 1C and Table 2C. Hematological diseases other than myeloid tumors, time from diagnosis to HSCT (<1 year), advanced disease stage at HSCT (intermediate and late), and poor PS were identified as significant factors for poor CIR. On the contrary, concomitant use of TBI contributed to a lower CIR. These data suggested that high NRM in the older group resulted in poor OS. Cause of death and complications including SOS Causes of death after HSCT are summarized in Table 3. In the older group, the relapse rate was lower than the other; however, no specific factors contributed to an increase in NRM among the older group. Therefore, we conducted a subgroup analysis to explore the factors that contribute to worse OS or NRM in the older group. The results of the univariate and multivariate analyses for OS and NRM in the group are shown in Supplemental Table 2A/B and Table 4A/B, respectively. Poor PS and use of additional chemotherapeutic drugs were common and significant factors for worse OS and NRM. Patients with additional chemotherapeutic drugs to FluBu4 experienced bleeding and thrombotic microangiopathy more frequently than those without them (data not shown). Approximately half of the older patients received TBI in addition to FluBu4; however, TBI was one of the poor prognostic factors for worse NRM in the multivariate analysis. Although TBI was not a significant poor prognostic factor for OS, more older patients with TBI developed SOS (1yCI of SOS, 5.0%, 95% CI 0.03–0.07, Figure 3) than those without TBI (1yCI of SOS, 1.5%, 95% CI 0.01–0.03). Furthermore, TBI was the only significant factor associated with the development of SOS in the multivariate analysis in the older group (P < 0.01). Cumulative incidence of acute and chronic GVHD according to age group No difference was found in grade II–IV and grade III–IV acute GVHD between the two groups (P = 0.79 and 0.97, Figure 4a and 4b, respectively). Their cumulative incidences up to day 100 after HSCT in the younger and older groups were 36.5% (95% CI 33.8%–39.1%) versus 35.2% (95% CI 32.3%–38.2%) and 12.9% (95% CI 11.1%–14.7%) versus 12.6% (95% CI 10.6%–14.8%), respectively. Similarly, no difference was found in all grade and extensive chronic GVHD between the two groups (P = 0.51 and 0.61, Figure 5a and 5b, respectively). Their cumulative incidences up to 3 years after HSCT in the younger and elderly groups were 36.0% (95% CI 33.3%–38.8%) versus 37.2% (95% CI 34.0%–40.3%) and 21.2% (95% CI 18.9%–23.5%) versus 22.0% (95% CI 19.4%–24.7%), respectively. Discussion In this study, we described worse OS in the older group (≥60 y/o) than in the other groups in HSCT with FluBu4-based regimen (Figure 1 and Table 2a), mainly due to increased NRM (Figure 2a and Table 2b). From the early period, when most transplants used conventional MAC, the increase in NRM with age was recognized, and until 2000, few opportunities were offered to transplant patients aged >50 years[29]. This increase in NRM was partly due to the toxicity of myeloablative the dose of TBI, which led to the introduction of chemotherapy-only conditioning regimen BuCy[30, 31]. In the era of oral busulfan, BuCy did not show a clear advantage over CyTBI[32]. However, since the availability of the intravenous formulation, BuCy was found to be comparable or superior to CyTBI in terms of complications and other issues in HSCT for myeloid malignancies[33]. Despite these improvements, the increase in BuCy-associated SOS and the increase in NRM in patients aged >50 years were still an issue. Increased transplant opportunities for older patients with hematologic malignancies have also led to the use of FluBu4, which replaces the Cy in BuCy with fludarabine[12, 34]. FluBu4 is generally used for transplant patients up to the age of 65–70 years [13, 35]; furthermore, HSCT with FluBu4 has been performed in real-world settings outside of clinical trials, even in patients aged >70 years[35]. In Japan, >40% of HSCT patients with a FluBu4-based regimen were ≥60 y/o (Table 1), and >10% of them were ≥65 y/o. However, whether the use of FluBu4 in patients who were >60 y/o has an acceptable safety profile and what complications may be increased have not been fully elucidated. In this study, increased NRM led to worse OS in the older group than in the younger group. Furthermore, excluding more high-risk patients (>65 y/o) from the older group, patients who were 60–65 y/o showed significantly worse NRM and OS than the younger group (Supplemental Figure 1a and 1b); this suggests that 60 y/o may be one of the criteria to assess the safety or tolerability for FluBu4 in HSCT. Despite poor NRM and OS in the older group, no significant increase in deaths caused by specific complications was observed in a review of causes of death in the Japanese transplant registry data. However, subgroup analysis of the older group showed that poor PS (2–4) and the use of additional chemotherapeutic drugs were common and significant factors for worse OS and NRM. FluBu4 is one of the most intense regimens that older people can receive, and our results that the increase in nonrecurrent deaths outweighed the reduction in recurrence rate led to the suggestion that it may be an unacceptable treatment for patients in poor general condition. In the older group that received additional chemotherapeutic drugs, CIR tended to remain high and NRM worsened, >40% of 3-year NRM, and the analysis in the advanced stage, who accounted for approximately one-third of all cases, showed similar results (data not shown). Therefore, older patients may be better off receiving exploratory treatment, such as participating in clinical trials for pretransplant disease control or posttransplant maintenance therapy in combination with non-MAC, instead of receiving MAC such as FluBu4 or additional chemotherapy to FluBu4 for disease control. Approximately half of the older patients received TBI with FluBu4 (Table 1). This resulted in an increase in NRM and a decrease in CIR, resulting in a nonsignificant change in OS compared with those without TBI (data not shown). SOS is a well-known side effect of busulfan, and TBI use was associated with a significant increase in SOS in the older group (Figure 3). TBI was the only negative prognostic factor for SOS in the multivariate analysis of a subgroup of older patients; a similar effect of TBI on SOS was not observed in the younger group. Based on these results, concomitant TBI must be avoided in older patients with risk factors for SOS as reported, such as worsening PS, history of gemtuzumab ozogamicin or inotuzumab ozogamicin use, iron overload, and liver disease[36]. In the multivariate analyses of OS, NRM, and CIR, a hematological disease other than a myeloid tumor was a significant poor prognostic factor in any of the analyses. This may be due to the limited efficacy of the myeloablative doses of busulfan for lymphoid tumors and patients with malignant lymphomas, which generally comprise more than half of this patient population, had been heavily treated before HSCT[37], resulting in the limited tolerability to FluBu4. For these patient groups, regardless of the age group, changing the HSCT strategy, including another conditioning regimen other than FluBu4, is recommended. In general, GVHD is a major cause of death other than relapse after HSCT. Although the risk of GVHD might increase in older people [38], this study observed no difference in acute and chronic GVHD, regardless of the grade. This study has several limitations, so the results must be interpreted with caution. Given the retrospective nature of this study, it was difficult to adequately assess some points. For example, which complications or conditions were responsible for the worsening of NRM in the older group were unclear. In addition, a post-hoc analysis was performed as the subgroup analysis of the older group because no difference was noted in the frequency of death or other complications between the two groups, and similar caution is required in interpreting the results. The worse OS in the older patients with FluBu4 shown in this study could be due to the shorter life expectancy of them compared to the other group, independent to conditioning regimens. It is difficult to adequately correct for that statistically. However, subgroup analyses of the older group have shown an increase of SOS in those with TBI and an increase in TMA in those with additional chemotherapy, suggesting an increase in transplant-related complications, which is not associated with their shorter life expectancy. Therefore, the use of FluBu4 in the older people should be performed with caution. Intravenous busulfan is a relatively safe method compared to the oral formulation, and it has been reported that the adjustment of intravenous busulfan by TDM contributes to reduced relapse rates and transplant-related mortality [39]. However, at the time of this study, TDM of busulfan was not approved for the Japanese health insurance system. Thus, most of the cases analyzed were likely to have been treated with fixed-dose busulfan. Furthermore, our dataset also did not include information on TDM, so the benefit of TDM could not be analyzed in this study. In conclusion, in HSCT with FluBu4-based regimens, the increase in NRM leads to poor OS in older people. Although confirming this research question in a large prospective or randomized controlled trial is desirable, the complex background of transplant patients makes this difficult in practice. Thus, careful assessment of the background of older patients and selection of a conditioning regimen, taking into account the related reports, are important. Declarations Acknowledgments The authors are grateful for the work of all physicians and data managers at the centers that contributed valuable data on transplantation to the JSTCT. They would also like to thank all members of the Transplant Registry Unified Management committees at JSTCT for their dedicated data management. Authorship A.S. designed the study, analyzed data, and wrote the manuscript. M.S., E.S., and H. Nakasone. advised on methods and revised the manuscript. N.U., K.F., H. Nakazawa, K.S., Y.K., T.K., T.I., O.H, A.I. T.W., and K.M. collected data and revised the manuscript. T.F. and J.T. managed the unified registry database and revised the manuscript. Y.A. collected data, revised the manuscript, and were responsible for data management at JSTCT. H. Nakasone was responsible for the working group. A.S., M.S. 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Blood 104:857–64. https://doi.org/10.1182/blood-2004-02-0414 Magenau JM, Braun T, Reddy P, et al (2015) Allogeneic transplantation with myeloablative FluBu4 conditioning improves survival compared to reduced intensity FluBu2 conditioning for acute myeloid leukemia in remission. Ann Hematol 94:1033–1041. https://doi.org/10.1007/s00277-015-2349-4 Corbacioglu S, Jabbour EJ, Mohty M (2019) Risk Factors for Development of and Progression of Hepatic Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome. Biol Blood Marrow Transplant 25:1271–1280. https://doi.org/10.1016/j.bbmt.2019.02.018 Shah NN, Hamadani M (2021) Is There Still a Role for Allogeneic Transplantation in the Management of Lymphoma? J Clin Oncol 39:487–498. https://doi.org/10.1200/JCO.20.01447 Nakane T, Fukuda T, Kanda J, et al (2015) Age influences post-graft-versus-host disease non-relapse mortality in adults with acute graft-versus-host disease of varying severity following allogeneic hematopoietic cell transplant. Leuk Lymphoma 56:2392–7. https://doi.org/10.3109/10428194.2015.1009056 Andersson BS, Thall PF, Valdez BC, et al (2017) Fludarabine with pharmacokinetically guided IV busulfan is superior to fixed-dose delivery in pretransplant conditioning of AML/MDS patients. Bone Marrow Transplant 52:580–587. https://doi.org/10.1038/bmt.2016.322 Tables Table 1. Patients’ background Patients’ group Younger (<60 y/o) Older (≥60 y/o) N % N % P-value Total 1,295 993 Age (y/o) Mean 49 63.6 <0.01* Median (range) 53 16–59 63 60–80 Sex Female 519 40.1% 336 33.8% <0.01* Male 776 59.9% 657 66.2% Diagnosis AML 731 56.4% 564 56.8% <0.01* ALL 54 4.2% 35 3.5% Other AL 43 3.3% 26 2.6% MDS 287 22.2% 285 28.7% CML 42 3.2% 24 2.4% MPN 31 2.4% 28 2.8% Lymphoma 102 7.9% 31 3.1% MM 5 0.4% 0 0.0% Disease status at HSCT 0 579 44.7% 403 40.6% 0.10 1 242 18.7% 213 21.5% 2 474 36.6% 377 38.0% Cell source BM 791 61.1% 728 73.3% <0.01* PB 504 38.9% 265 26.7% Donor type MRD/MUD 774 59.8% 640 64.5% 0.02* Others 521 40.2% 353 35.5% Sex comb. F to M 1,018 78.6% 782 78.8% 0.93 Others 277 21.4% 211 21.2% Dx to HSCT (day) Median (range) 234 157–497 221.5 163.5–433 180 845 65.3% 670 67.5% Missing 1 0.1% 1 0.1% ABO Major 222 17.1% 180 18.1% 0.59 Bidirectional 105 8.1% 92 9.3% Minor 250 19.3% 174 17.5% Match 717 55.4% 545 54.9% Missing 1 0.1% 2 0.2% Use of ATG/ALG No 1,109 85.6% 869 87.5% 0.19 Yes 186 14.4% 124 12.5% TBI No 776 59.9% 554 55.8% 0.05 Yes 519 40.1% 439 44.2% Add. chem. drug No 1,013 78.2% 870 87.6% <0.01 Yes 282 21.8% 123 12.4% Performance status 0–1 1,183 91.4% 885 89.1% 0.20 2–4 111 8.6% 107 10.8% Missing 1 0.1% 1 0.1% HCT-CI score 0–2 1,029 79.5% 788 79.4% 0.95 ≥3 266 20.5% 205 20.6% CMV risk No 91 7.0% 61 6.1% 0.45 Yes 1,146 88.5% 895 90.1% Missing 58 4.5% 37 3.7% HSCT year Before 2013 435 33.6% 300 30.2% 0.09 2013 or later 860 66.4% 693 69.8% ABO, ABO blood group mismatch pattern between the donor and the recipient; Add. chem. drug, additional chemotherapeutic drug; ALG, anti-lymphocyte globulin; ALL, acute lymphoblastic leukemia; AML, acute myeloid leukemia; ATG, anti-thymocyte globulin; BM, bone marrow; CML, chronic myeloid leukemia; CMV, cytomegalovirus; comb., combination; Disease stage, categorized according to EBMT risk score [20]; Dx, diagnosis; F to M, HSCT from female donor to male recipient; HCT-CI, hematopoietic cell transplantation-specific comorbidity index; HSCT, hematopoietic stem cell transplantation; MDS, myelodysplastic syndrome; MM, multiple myeloma; MPN, myeloproliferative neoplasm; MRD, matched-related donor; MUD, matched-unrelated donor; Other AL, other types of acute leukemia; PB, peripheral blood; TBI, total body irradiation; y/o, years old; *, significant difference (p<0.05) Table 2a. Multivariate analysis for OS Factor HR 95% CI P-value Lower Upper Age <60 y/o Ref. − − − ≥60 y/o 1.35 1.20 1.51 <0.01* Disease Myeloid Ref. − − − Others 1.45 1.24 1.70 <0.01* Dx to HSCT 1 y 0.82 0.72 0.94 <0.01* Disease stage at HSCT Early Ref. − − − Intermediate 1.09 0.91 1.31 0.36 Late 2.12 1.85 2.42 <0.01* Donor type MRD or MUD Ref. − − − Others 1.17 1.04 1.31 0.01* F to M No Ref. − − − Yes 1.15 1.00 1.32 0.04* Performance status 0–1 Ref. − − − 2–4 2.21 1.87 2.62 <0.01* HCT-CI 0–2 Ref. − − − ≥3 1.07 0.93 1.23 0.35 CI, confidence interval; Disease stage, categorized according to EBMT risk score [20]; wDx, diagnosis; F to M, HSCT from female donor to male recipient; HCT-CI, hematopoietic cell transplantation-specific comorbidity index; HR, hazard ratio; HSCT, hematopoietic stem cell transplantation; MRD, matched-related donor; MUD, matched-unrelated donor; OS, overall survival; Ref., reference; y/o, years old; *, significant difference (p<0.05) Table 2b. Multivariate analysis for NRM Factor HR 95% CI P-value Lower Upper Age <60 y/o Ref. − − − ≥60 y/o 1.41 1.20 1.67 <0.01* Disease Myeloid Ref. − − − Others 1.30 1.03 1.63 0.03* Dx to HSCT 1 year 1.28 1.08 1.52 <0.01* Donor type MRD or MUD Ref. − − − Others 1.21 1.02 1.45 0.03* Performance status 0–1 Ref. − − − 2–4 1.44 1.11 1.87 0.01* Use of ATG/ALG None Ref. − − − Yes 0.72 0.55 0.94 0.02* Use of TBI None Ref. − − − Yes 1.23 1.04 1.45 0.02* ALG, anti-lymphocyte globulin; ATG, anti-thymocyte globulin; CI, confidence interval; Dx, diagnosis; HR, hazard ratio; HSCT, hematopoietic stem cell transplantation; MRD, matched-related donor; MUD, matched-unrelated donor; NRM, non-relapse mortality; Ref., reference; TBI, total body irradiation; y/o, years old; *, significant difference (p<0.05) Table 2c. Multivariate analysis for CIR Factor HR 95% CI P-value Lower Upper Disease Myeloid Ref. − − − Others 1.42 1.16 1.74 1 y 0.55 0.46 0.66 <0.01* Disease stage at HSCT Early Ref. − − − Intermediate 1.73 1.36 2.19 <0.01* Late 3.09 2.61 3.67 <0.01* Cell source BM Ref. − − − PB 1.03 0.88 1.20 0.69 Performance status 0–1 Ref. − − − 2–4 1.52 1.23 1.88 <0.01* Use of TBI None Ref. − − − Yes 0.84 0.72 0.97 0.02* BM, bone marrow; CI, confidence interval; CIR, cumulative incidence of relapse; Disease stage, categorized according to EBMT risk score [20]; Dx, diagnosis; HR, hazard ratio; HSCT, hematopoietic stem cell transplantation; PB, peripheral blood; Ref., reference; TBI, total body irradiation; *, significant difference (p<0.05) Table 3. Causes of death Causes of death Patients’ group Younger (<60 y/o) Older (≥60 y/o) Relapse 281 29.1% 242 27.8% Acute GVHD 70 7.3% 65 7.5% Chronic GVHD 55 5.7% 46 5.3% Rejection 24 2.5% 18 2.1% Bacterial infection 110 11.4% 105 12.1% Other types of infections 98 10.2% 100 11.5% TMA 34 3.5% 33 3.8% Bleeding 48 5.0% 42 4.8% Noninfectious lung disease 116 12.0% 94 10.8% Liver disease (including SOS) 36 3.7% 36 4.1% Other types of organ damage 74 7.7% 72 8.3% Other cause 18 1.9% 18 2.1% GVHD, graft versus host disease; SOS, sinusoidal obstruction syndrome; TMA, thrombotic microangiopathy; y/o, years old Table 4a. Multivariate analysis for OS in the older group Factor HR 95% CI P-value Lower Upper Dx to HSCT 1 year 0.81 0.66 0.98 0.03* Disease stage at HSCT Early Ref. - - - Intermediate 1.06 0.82 1.37 0.66 Late 2.08 1.71 2.53 <0.01* Cell source BM Ref. - - - PB 0.97 0.80 1.17 0.71 F to M No Ref. - - - Yes 1.19 0.98 1.45 0.08 Performance status 0–1 Ref. - - - 2–4 2.34 1.86 2.96 <0.01* Use of add. chem None Ref. - - - Yes 1.35 1.06 1.70 0.01* Add. chem. drug, additional chemotherapeutic drug; BM, bone marrow; CI, confidence interval; Disease stage, categorized according to EBMT risk score [20]; Dx, diagnosis; F to M, HSCT from female donor to male recipient; HR, hazard ratio; HSCT, hematopoietic stem cell transplantation; OS, overall survival; PB, peripheral blood; Ref., reference; *, significant difference (p<0.05) Table 4b. Multivariate analysis for NRM in the older group Factor HR 95% CI P-value Lower Upper Disease Myeloid Ref. − − − Others 1.44 1.01 2.05 0.04* Dx to HSCT 1y 1.40 1.11 1.78 0.01* Performance status 0–1 Ref. − − − 2–4 1.32 0.92 1.89 0.13* Use of TBI None Ref. − − − Yes 1.45 1.15 1.82 <0.01* Use of add. chem. drug None Ref. − − − Yes 1.74 1.25 2.42 <0.01* Add. chem. drug, additional chemotherapeutic drug; CI, confidence interval; Dx, diagnosis; HR, hazard ratio; HSCT, hematopoietic stem cell transplantation; NRM, non-relapse mortality; Ref., reference; TBI, total body irradiation; *, significant difference (p<0.05) Additional Declarations Competing interest reported. A.S. has received honoraria from Otsuka Pharmaceutical Co. and Sanofi K.K. N.U. has received honoraria from Otsuka Pharmaceutical Co. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4227690","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":297233025,"identity":"65b85065-21f2-4e03-a5c4-12c153eacd8e","order_by":0,"name":"Akihito 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Transplantation","correspondingAuthor":false,"prefix":"","firstName":"Yoshiko","middleName":"","lastName":"Atsuta","suffix":""},{"id":297233084,"identity":"5bf94978-783b-47a1-8229-6d23a81530c6","order_by":17,"name":"Hideki Nakasone","email":"","orcid":"","institution":"Jichi Medical University Saitama Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Hideki","middleName":"","lastName":"Nakasone","suffix":""}],"badges":[],"createdAt":"2024-04-06 13:44:29","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4227690/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4227690/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":55765513,"identity":"7858625b-6e61-4bd5-adb8-24bd034e4689","added_by":"auto","created_at":"2024-05-02 20:07:19","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":49071,"visible":true,"origin":"","legend":"\u003cp\u003eOverall survival\u003c/p\u003e\n\u003cp\u003eKaplan–Meier curves for overall survival after HSCT, according to the patients’ age groups (younger group; \u0026lt;60 year-old, older group; 60 year-old or older). HSCT; hematopoietic stem cell transplantation.\u003c/p\u003e","description":"","filename":"Fig1.png","url":"https://assets-eu.researchsquare.com/files/rs-4227690/v1/ee074a65d089dd193547234d.png"},{"id":55765516,"identity":"ebdf26fd-a015-489b-aa08-84021ec1b9b9","added_by":"auto","created_at":"2024-05-02 20:07:20","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":94652,"visible":true,"origin":"","legend":"\u003cp\u003eNon-relapse mortality and cumulative incidence of relapse\u003c/p\u003e\n\u003cp\u003eThe graphs showed (a) non-relapse mortality after HSCT and (b) cumulative incidence of relapse, according to the patients’ age groups (younger group; \u0026lt;60 year-old, older group; 60 year-old or older). These figures were estimated by Fine and Gray methods. HSCT; hematopoietic stem cell transplantation.\u003c/p\u003e","description":"","filename":"Fig2a.png","url":"https://assets-eu.researchsquare.com/files/rs-4227690/v1/e62ac590de3f018da4ab172d.png"},{"id":55765514,"identity":"a590462c-9936-4550-b96a-eb71bdaf1c90","added_by":"auto","created_at":"2024-05-02 20:07:19","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":46187,"visible":true,"origin":"","legend":"\u003cp\u003eCumulative incidence of SOS in the older group\u003c/p\u003e\n\u003cp\u003eThe graphs showed cumulative incidence of SOS up to one year after HSCT, according to the patients with or without TBI. This figure was estimated by Fine and Gray methods. SOS; sinusoidal obstruction syndrome, HSCT; hematopoietic stem cell transplantation, w/o; without, TBI; total body irradiation.\u003c/p\u003e","description":"","filename":"Fig3.png","url":"https://assets-eu.researchsquare.com/files/rs-4227690/v1/9461493a9cc05a1988e7a5c3.png"},{"id":55765515,"identity":"ff2b4716-0294-425c-96d3-69cdf1fea3f3","added_by":"auto","created_at":"2024-05-02 20:07:19","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":95960,"visible":true,"origin":"","legend":"\u003cp\u003eCumulative incidence of acute GVHD\u003c/p\u003e\n\u003cp\u003eThe graphs showed cumulative incidence of acute GVHD up to day 100 after HSCT, according to the patients’age groups (younger group; \u0026lt;60 year-old, older group; 60 year-old or older); (a) grade II to IV acute GVHD, (b) grade III to IV acute GVHD. These figures were estimated by Fine and Gray methods. GVHD; graft versus host disease, HSCT; hematopoietic stem cell transplantation.\u003c/p\u003e","description":"","filename":"Fig4a.png","url":"https://assets-eu.researchsquare.com/files/rs-4227690/v1/8d13b4471b0c1b9fca44640b.png"},{"id":55765512,"identity":"040d625d-85b5-4bf6-92f5-5e0ec3ad549d","added_by":"auto","created_at":"2024-05-02 20:07:19","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":92841,"visible":true,"origin":"","legend":"\u003cp\u003eCumulative incidence of chronic GVHD\u003c/p\u003e\n\u003cp\u003eThe graphs showed cumulative incidence of chronic GVHD, according to the patients’age groups (younger group; \u0026lt;60 year-old, older group; 60 year-old or older); (a) all chronic GVHD, (b) extensive chronic GVHD. These figures were estimated by Fine and Gray methods. GVHD; graft versus host disease, HSCT; hematopoietic stem cell transplantation.\u003c/p\u003e","description":"","filename":"Fig5a.png","url":"https://assets-eu.researchsquare.com/files/rs-4227690/v1/1a3a2f3cd98a6c5cabb0a1ee.png"},{"id":64785574,"identity":"3f74b579-18ec-4ed1-8ed4-926c23b3b671","added_by":"auto","created_at":"2024-09-18 19:06:40","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1237045,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4227690/v1/7e88a096-c8fc-4bc9-b238-d4ea70005141.pdf"},{"id":55765517,"identity":"618e4cb0-f312-4649-9d61-b5cc5a702b90","added_by":"auto","created_at":"2024-05-02 20:07:22","extension":"docx","order_by":10,"title":"","display":"","copyAsset":false,"role":"supplement","size":332257,"visible":true,"origin":"","legend":"","description":"","filename":"WG20FluBu4AnnHemSup.docx","url":"https://assets-eu.researchsquare.com/files/rs-4227690/v1/ba74e299fd79df4c35fd7420.docx"}],"financialInterests":"Competing interest reported. A.S. has received honoraria from Otsuka Pharmaceutical Co. and Sanofi K.K. N.U. has received honoraria from Otsuka Pharmaceutical Co.","formattedTitle":"Increased non-relapse mortality in older people with allogeneic hematopoietic stem cell transplantation using fludarabine and myeloablative dose of busulfan-based regimen","fulltext":[{"header":"Introduction","content":"\u003cp\u003eDespite modern advances in molecular-targeted drugs, monoclonal antibody, immunotherapies, relapsed and refractory hematological malignancies remain major problems[1\u0026ndash;6]. Allogeneic hematopoietic stem cell transplantation (HSCT) remains an important curative treatment for relapsed and refractory hematological malignancies. In the early days, HSCT using bone myeloablative conditioning regimens (MAC) such as cyclophosphamide and total body irradiation (CyTBI) or busulfan and cyclophosphamide (BuCy) has been the standard method[7\u0026ndash;9]; however, MAC was not feasible for patients with organ damage or older people [10]. In consideration of this concern, various reduced-intensity conditioning regimens (RICs) were developed; currently, HSCT for older patients with leukemia has mainly used RIC[11].\u003c/p\u003e\n\u003cp\u003eFludarabine and four days of busulfan (FluBu4), which consists of fludarabine combined with a myeloablative dose of busulfan, has been frequently used as a less toxic regimen than conventional MAC while maintaining antitumor effects on hematopoietic malignancies[11, 12]. FluBu4 showed an antitumor effect on myeloid tumors comparable to BuCy while reducing non-relapse mortality (NRM)[13]. Conventional MAC is indicated up to age 50\u0026ndash;60 years[14], whereas FluBu4 has been used at older ages. However, problems potentially associated with FluBu4 in older people have not been sufficiently examined, and many issues must be considered, including the upper age limit for this therapy, whether to administer FluBu4 in addition to TBI and chemotherapy in older people, and FluBu4-associated complications such as sinusoidal obstruction syndrome (SOS) that need particular attention.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTherefore, this study investigated this issue using data from the Transplant Registry Unified Management Program (TRUMP) of the Japanese Data Center for Hematopoietic Cell Transplantation[15\u0026ndash;17] and divided patients receiving FluBu4-based regimen at HSCT into two groups by 60 years old (y/o).\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003ePatients and data collection\u003c/p\u003e\n\u003cp\u003eThis multicenter retrospective study used data from TRUMP on behalf of the Transplant Complication Working Group of the Japanese Society for Transplantation and Cellular Therapy (JSTCT). v This study was conducted in accordance with the Declaration of Helsinki and was approved by the institutional review boards of Tokyo Women\u0026rsquo;s Medical University Hospital and the JSTCT.\u003c/p\u003e\n\u003cp\u003ePatients aged \u0026gt;15 years with hematological malignancies, who received the first HSCT between 2006 and 2017 in Japan, were included. They all received Flu/Bu4 (total intravenous busulfan dose of 11.2\u0026ndash;16 mg/kg or equivalent) at HSCT. Patients who received TBI, anti-thymocyte globulin (ATG), anti-lymphocyte globulin (ALG), or other chemotherapeutic drugs were also included. The patients who received allo-HSCT from cord-blood donors were excluded.\u003c/p\u003e\n\u003cp\u003eDefinition and statistical analysis\u003c/p\u003e\n\u003cp\u003eTo reflect current practice in Japan, human leukocyte antigen (HLA) matching in related donors was assessed by serological data for HLA-A, HLA-B, and HLA-DR loci. An HLA match in related donors indicates that the recipient\u0026rsquo;s antigens were identical to the donor\u0026rsquo;s antigens at 6/6 loci. In unrelated donors, it was assessed by genotyping for HLA-A, HLA-B, HLA-C, and HLA-DR loci. In unrelated donors, an HLA match indicates that the recipient\u0026rsquo;s allele was identical to the donor\u0026rsquo;s allele at 8/8 loci.\u003c/p\u003e\n\u003cp\u003eNeutrophil engraftment was defined as a neutrophil count of \u0026ge;500/mm\u003csup\u003e3\u003c/sup\u003e of blood for 3 days. Acute and chronic graft versus host disease (GVHD) were graded by each physician in accordance with previous reports[18, 19]. The disease stage of hematological malignancies at HSCT was classified into three categories (early, intermediate, and late) in accordance with the European Group for Blood and Marrow Transplantation risk score[20]. Hematopoietic cell transplantation-specific comorbidity index (HCT-CI) and performance status (PS) at HSCT were estimated as described previously[21, 22]. SOS was diagnosed by a primary physician at each institution with reference to the Baltimore or the modified Seattle criteria[23, 24]. If the patient or the donor tested positive for anti-cytomegalovirus (CMV) antibodies at HSCT, the patient was considered at risk for CMV infection. In analyzing the cause of death, descriptions of the primary and secondary causes of death in the registry data are combined; because in some cases more than one entry was made for a single patient, no tests for significant differences were performed.\u003c/p\u003e\n\u003cp\u003eOverall survival (OS) was defined as the time from the date of HSCT until death or last observation and estimated using the Kaplan\u0026ndash;Meier method[25]. The difference in survival curves was assessed with the log-rank test. Cox proportional hazards regression model was used to identify OS-associated prognostic factors in the univariate and multivariate analyses. Factors that showed a significant effect (P \u0026lt; 0.05) in the univariate analysis were selected for the multivariate analysis.\u003c/p\u003e\n\u003cp\u003eNRM was defined as death without relapse after allo-HSCT. NRM and cumulative incidence of relapse (CIR), neutrophil engraftment, acute GVHD, chronic GVHD, and SOS were assessed with Gray\u0026rsquo;s method[26]. In the NRM and CIR analysis, the other was assumed as a competing event. In the analysis of the cumulative incidence of acute GVHD (grades II\u0026ndash;IV and grades III\u0026ndash;IV), chronic GVHD (all grades and extensive), neutrophil engraftment, and SOS, death from any cause was assumed as a competing event. Fine and Gray proportional hazards regression model was used to identify prognostic factors associated with NRM and CIR in the univariate and multivariate analyses[27]. In the multivariate analysis of NRM and CIR, the factors selected were those that showed a significant effect (P \u0026lt; 0.05) in the univariate analysis.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Categorical and continuous variables were compared using chi-squared tests and Student\u0026rsquo;s t-tests (two-sided), respectively. \u003cem\u003eP\u0026nbsp;\u003c/em\u003evalues \u0026lt;0.05 were considered statistically significant.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; The dataset for this study was edited using STATA version 16.1 (StataCorp LLC, TX, USA), and statistical analyses were performed using EZR (Saitama Medical Center, Jichi Medical University, Saitama, Japan; http://www.jichi.ac.jp/saitama-sct/SaitamaHP.files/statmedEN.html), which is a graphical user interface for R (The R Foundation for Statistical Computing, Vienna, Austria, version 4.0.3)[28].\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eCharacteristics of the patients who received HSCT using FluBu4\u003c/p\u003e\n\u003cp\u003eThe median follow-up of survivors was 30.5 (range 15\u0026ndash;4109) months. Patients\u0026rsquo; background according to their age groups (younger group, \u0026lt;60 y/o; older group, \u0026ge;60 y/o) are shown in Table 1. The median age of the patients was 58 (range 16\u0026ndash;80) years, and 43.4% of the patients were \u0026ge;60 y/o. Of the 2,288 patients, 62.6% were male. Patients were diagnosed with myeloid (87.1%), lymphoid (9.1%), and other (3.0%) malignancies. Approximately two-thirds of the patients (66.4%) received bone marrow transplantation, and 584 (25.5%) and 830 (36.3%) received HSCT from matched-related donors and 8/8 matched-unrelated donors. Although this study allowed the use of intravenous busulfan up to a total dose of 16 mg/kg, 2244 (98.1%) actually analyzed used busulfan at a total dose of 12.8 mg/kg or less. Dose adjustment of busulfan by therapeutic dose monitoring (TDM) in adult HSCT is not commonly performed in Japan, and there were no data on this practice in this dataset.\u003c/p\u003e\n\u003cp\u003eThe median day of neutrophil engraftment was day 16 in both groups. The cumulative incidence of neutrophil engraftment at day 100 was 96.3% (95% confidence interval [CI]; 95.1%\u0026ndash;97.2%) in the younger group and 95.5% (95% CI 94.0%\u0026ndash;96.6%) in the older group (P = 0.053). In addition, no significant difference was found in the case of secondary graft failure in both groups (P = 0.38).\u003c/p\u003e\n\u003cp\u003eSurvival analysis (OS, NRM, and CIR) according to age groups\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe 3-year OS after HSCT in the older group was significantly worse than that in the younger group (39.9% [95% CI 36.5%\u0026ndash;43.2%] versus 48.5% [95% CI 45.4%\u0026ndash;51.4%], P \u0026lt; 0.01, Figure 1). While the 3-year NRM in the older group was significantly higher than for the younger group (30.9% [95% CI 27.9%\u0026ndash;34.0%] versus 23.0% [95% CI 20.6%\u0026ndash;25.5%], P \u0026lt; 0.01, Figure 2a), and the 3-year CIR was comparable between the two groups (32.1% [95% CI 29.1%\u0026ndash;35.1%] versus 32.1% [95% CI 29.4%\u0026ndash;35.7%], P = 0.67, Figure 2b).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn addition, the 3-year NRM for patients aged \u0026gt;65 years was 35.7% (95% CI 29.7%\u0026ndash;42.2%), and for patients aged 60\u0026ndash;65 years, excluding this high-risk patient group from the older group, the 3-year NRM was 29.4% (95% CI 26.0%\u0026ndash;33.0%). This worsening of NRM in patients aged 60\u0026ndash;65 years was significantly different from that in the younger group (P \u0026lt; 0.01). The OS was significantly worse in the 60\u0026ndash;65 age group than that in the younger group (P \u0026lt; 0.01, Supplemental Figures 1a and 1b) because of this change in NRM as CIR was comparable in these three groups (Supplemental Figure 1c).\u003c/p\u003e\n\u003cp\u003eAccording to the multivariate analysis, increased patient age (\u0026ge;60 years), hematological diseases other than myeloid tumors, time from diagnosis to HSCT (\u0026lt;1 year), advanced disease stage at HSCT (late), HLA-mismatched donor, sex combination (HSCT from female donor to male recipient), poor PS (2\u0026ndash;4), and high HCT-CI score (\u0026ge;3) were significantly associated with an increased risk of poor OS (Table 2A). The univariate analysis for OS is shown in Supplemental Table 1A. Regarding NRM, the results of the univariate and multivariate analyses are shown in Supplemental Table 2B and Table 2B. Increased patient age (\u0026ge;60 years), hematological diseases other than myeloid tumors, HLA-mismatched donor, and poor PS were identified as significant factors for poor NRM, which were the common prognostic factors found in the OS analysis. Regarding CIR, the results of the univariate and multivariate analyses are shown in Supplemental Table 1C and Table 2C. Hematological diseases other than myeloid tumors, time from diagnosis to HSCT (\u0026lt;1 year), advanced disease stage at HSCT (intermediate and late), and poor PS were identified as significant factors for poor CIR. On the contrary, concomitant use of TBI contributed to a lower CIR. These data suggested that high NRM in the older group resulted in poor OS.\u003c/p\u003e\n\u003cp\u003eCause of death and complications including SOS\u003c/p\u003e\n\u003cp\u003eCauses of death after HSCT are summarized in Table 3. In the older group, the relapse rate was lower than the other; however, no specific factors contributed to an increase in NRM among the older group. Therefore, we conducted a subgroup analysis to explore the factors that contribute to worse OS or NRM in the older group. The results of the univariate and multivariate analyses for OS and NRM in the group are shown in Supplemental Table 2A/B\u0026nbsp;and Table 4A/B, respectively. Poor PS and use of additional chemotherapeutic drugs were common and significant factors for worse OS and NRM. Patients with additional chemotherapeutic drugs to FluBu4 experienced bleeding and thrombotic microangiopathy more frequently than those without them (data not shown).\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Approximately half of the older patients received TBI in addition to FluBu4; however, TBI was one of the poor prognostic factors for worse NRM in the multivariate analysis. Although TBI was not a significant poor prognostic factor for OS, more older patients with TBI developed SOS (1yCI of SOS, 5.0%, 95% CI 0.03\u0026ndash;0.07, Figure 3) than those without TBI (1yCI of SOS, 1.5%, 95% CI 0.01\u0026ndash;0.03). Furthermore, TBI was the only significant factor associated with the development of SOS in the multivariate analysis in the older group (P \u0026lt; 0.01).\u003c/p\u003e\n\u003cp\u003eCumulative incidence of acute and chronic GVHD according to age group\u003c/p\u003e\n\u003cp\u003eNo difference was found in grade II\u0026ndash;IV and grade III\u0026ndash;IV acute GVHD between the two groups (P = 0.79 and 0.97, Figure 4a and 4b, respectively). Their cumulative incidences up to day 100 after HSCT in the younger and older groups were 36.5% (95% CI 33.8%\u0026ndash;39.1%) versus 35.2% (95% CI 32.3%\u0026ndash;38.2%) and 12.9% (95% CI 11.1%\u0026ndash;14.7%) versus 12.6% (95% CI 10.6%\u0026ndash;14.8%), respectively.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Similarly, no difference was found in all grade and extensive chronic GVHD between the two groups (P = 0.51 and 0.61, Figure 5a and 5b, respectively). Their cumulative incidences up to 3 years after HSCT in the younger and elderly groups were 36.0% (95% CI 33.3%\u0026ndash;38.8%) versus 37.2% (95% CI 34.0%\u0026ndash;40.3%) and 21.2% (95% CI 18.9%\u0026ndash;23.5%) versus 22.0% (95% CI 19.4%\u0026ndash;24.7%), respectively.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;In this study, we described worse OS in the older group (\u0026ge;60 y/o) than in the other groups in HSCT with FluBu4-based regimen (Figure 1 and Table 2a), mainly due to increased NRM (Figure 2a and Table 2b). From the early period, when most transplants used conventional MAC, the increase in NRM with age was recognized, and until 2000, few opportunities were offered to transplant patients aged \u0026gt;50 years[29]. This increase in NRM was partly due to the toxicity of myeloablative the dose of TBI, which led to the introduction of chemotherapy-only conditioning regimen BuCy[30, 31].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;In the era of oral busulfan, BuCy did not show a clear advantage over CyTBI[32]. However, since the availability of the intravenous formulation, BuCy was found to be comparable or superior to CyTBI in terms of complications and other issues in HSCT for myeloid malignancies[33]. Despite these improvements, the increase in BuCy-associated SOS and the increase in NRM in patients aged \u0026gt;50 years were still an issue. Increased transplant opportunities for older patients with hematologic malignancies have also led to the use of FluBu4, which replaces the Cy in BuCy with fludarabine[12, 34].\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;FluBu4 is generally used for transplant patients up to the age of 65\u0026ndash;70 years [13, 35]; furthermore, HSCT with FluBu4 has been performed in real-world settings outside of clinical trials, even in patients aged \u0026gt;70 years[35]. In Japan, \u0026gt;40% of HSCT patients with a FluBu4-based regimen were \u0026ge;60 y/o (Table 1), and \u0026gt;10% of them were \u0026ge;65 y/o. However, whether the use of FluBu4 in patients who were \u0026gt;60 y/o has an acceptable safety profile and what complications may be increased have not been fully elucidated. In this study, increased NRM led to worse OS in the older group than in the younger group. Furthermore, excluding more high-risk patients (\u0026gt;65 y/o) from the older group, patients who were 60\u0026ndash;65 y/o showed significantly worse NRM and OS than the younger group (Supplemental Figure 1a and 1b); this suggests that 60 y/o may be one of the criteria to assess the safety or tolerability for FluBu4 in HSCT.\u003c/p\u003e\n\u003cp\u003eDespite poor NRM and OS in the older group, no significant increase in deaths caused by specific complications was observed in a review of causes of death in the Japanese transplant registry data. However, subgroup analysis of the older group showed that poor PS (2\u0026ndash;4) and the use of additional chemotherapeutic drugs were common and significant factors for worse OS and NRM. FluBu4 is one of the most intense regimens that older people can receive, and our results that the increase in nonrecurrent deaths outweighed the reduction in recurrence rate led to the suggestion that it may be an unacceptable treatment for patients in poor general condition. In the older group that received additional chemotherapeutic drugs, CIR tended to remain high and NRM worsened, \u0026gt;40% of 3-year NRM, and the analysis in the advanced stage, who accounted for approximately one-third of all cases, showed similar results (data not shown). Therefore, older patients may be better off receiving exploratory treatment, such as participating in clinical trials for pretransplant disease control or posttransplant maintenance therapy in combination with non-MAC, instead of receiving MAC such as FluBu4 or additional chemotherapy to FluBu4 for disease control.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Approximately half of the older patients received TBI with FluBu4 (Table 1). This resulted in an increase in NRM and a decrease in CIR, resulting in a nonsignificant change in OS compared with those without TBI (data not shown). SOS is a well-known side effect of busulfan, and TBI use was associated with a significant increase in SOS in the older group (Figure 3). TBI was the only negative prognostic factor for SOS in the multivariate analysis of a subgroup of older patients; a similar effect of TBI on SOS was not observed in the younger group. Based on these results, concomitant TBI must be avoided in older patients with risk factors for SOS as reported, such as worsening PS, history of gemtuzumab ozogamicin or inotuzumab ozogamicin use, iron overload, and liver disease[36].\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;In the multivariate analyses of OS, NRM, and CIR, a hematological disease other than a myeloid tumor was a significant poor prognostic factor in any of the analyses. This may be due to the limited efficacy of the myeloablative doses of busulfan for lymphoid tumors and patients with malignant lymphomas, which generally comprise more than half of this patient population, had been heavily treated before HSCT[37], resulting in the limited tolerability to FluBu4. For these patient groups, regardless of the age group, changing the HSCT strategy, including another conditioning regimen other than FluBu4, is recommended.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;In general, GVHD is a major cause of death other than relapse after HSCT. Although the risk of GVHD might increase in older people [38], this study observed no difference in acute and chronic GVHD, regardless of the grade.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;This study has several limitations, so the results must be interpreted with caution. Given the retrospective nature of this study, it was difficult to adequately assess some points. For example, which complications or conditions were responsible for the worsening of NRM in the older group were unclear. In addition, a post-hoc analysis was performed as the subgroup analysis of the older group because no difference was noted in the frequency of death or other complications between the two groups, and similar caution is required in interpreting the results. The worse OS in the older patients with FluBu4 shown in this study could be due to the shorter life expectancy of them compared to the other group, independent to conditioning regimens. It is difficult to adequately correct for that statistically. However, subgroup analyses of the older group have shown an increase of SOS in those with TBI and an increase in TMA in those with additional chemotherapy, suggesting an increase in transplant-related complications, which is not associated with their shorter life expectancy. Therefore, the use of FluBu4 in the older people should be performed with caution.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Intravenous busulfan is a relatively safe method compared to the oral formulation, and it has been reported that the adjustment of intravenous busulfan by TDM contributes to reduced relapse rates and transplant-related mortality [39]. However, at the time of this study, TDM of busulfan was not approved for the Japanese health insurance system. Thus, most of the cases analyzed were likely to have been treated with fixed-dose busulfan. Furthermore, our dataset also did not include information on TDM, so the benefit of TDM could not be analyzed in this study.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; In conclusion, in HSCT with FluBu4-based regimens, the increase in NRM leads to poor OS in older people. Although confirming this research question in a large prospective or randomized controlled trial is desirable, the complex background of transplant patients makes this difficult in practice. Thus, careful assessment of the background of older patients and selection of a conditioning regimen, taking into account the related reports, are important.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors are grateful for the work of all physicians and data managers at the centers that contributed valuable data on transplantation to the JSTCT. They would also like to thank all members of the Transplant Registry Unified Management committees at JSTCT for their dedicated data management.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthorship\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA.S. designed the study, analyzed data, and wrote the manuscript. M.S., E.S., and H. Nakasone. advised on methods and revised the manuscript. N.U., K.F., H. Nakazawa, K.S., Y.K., T.K., T.I., O.H, A.I. T.W., and K.M. collected data and revised the manuscript. T.F. and J.T. managed the unified registry database and revised the manuscript. Y.A. collected data, revised the manuscript, and were responsible for data management at JSTCT. H. Nakasone was responsible for the working group. A.S., M.S. E.S., and H. Nakasone were members of the working group.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding information\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported in part by the Practical Research Project for Allergic Diseases and Immunology (Research Technology of Medical Transplantation) from Japan Agency for Medical Research and Development, AMED (Grant Number JP21ek0510034).\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eSermer D, Brentjens R (2019) CAR T-cell therapy: Full speed ahead. Hematol Oncol 37 Suppl 1:95\u0026ndash;100. https://doi.org/10.1002/hon.2591\u003c/li\u003e\n\u003cli\u003eLiu Y, Barta SK (2019) Diffuse large B-cell lymphoma: 2019 update on diagnosis, risk stratification, and treatment. Am J Hematol 94:604\u0026ndash;616. https://doi.org/10.1002/ajh.25460\u003c/li\u003e\n\u003cli\u003eHanel W, Epperla N (2020) Emerging therapies in mantle cell lymphoma. J Hematol Oncol 13:79. https://doi.org/10.1186/s13045-020-00914-1\u003c/li\u003e\n\u003cli\u003eVan Der Weyden C, Dickinson M, Whisstock J, Prince HM (2019) Brentuximab vedotin in T-cell lymphoma. Expert Rev Hematol 12:5\u0026ndash;19. https://doi.org/10.1080/17474086.2019.1558399\u003c/li\u003e\n\u003cli\u003eMottok A, Steidl C (2018) Biology of classical Hodgkin lymphoma: implications for prognosis and novel therapies. Blood 131:1654\u0026ndash;1665. https://doi.org/10.1182/blood-2017-09-772632\u003c/li\u003e\n\u003cli\u003eCheah CY, Fowler NH (2018) Novel agents for relapsed and refractory follicular lymphoma. Best Pract Res Clin Haematol 31:41\u0026ndash;48. https://doi.org/10.1016/j.beha.2017.11.003\u003c/li\u003e\n\u003cli\u003eTutschka PJ, Copelan EA, Klein JP (1987) Bone marrow transplantation for leukemia following a new busulfan and cyclophosphamide regimen. Blood 70:1382\u0026ndash;8\u003c/li\u003e\n\u003cli\u003eSantos GW, Tutschka PJ, Brookmeyer R, et al (1983) Marrow transplantation for acute nonlymphocytic leukemia after treatment with busulfan and cyclophosphamide. N Engl J Med 309:1347\u0026ndash;53. https://doi.org/10.1056/NEJM198312013092202\u003c/li\u003e\n\u003cli\u003eThomas ED, Buckner CD, Banaji M, et al (1977) One hundred patients with acute leukemia treated by chemotherapy, total body irradiation, and allogeneic marrow transplantation. Blood 49:511\u0026ndash;33\u003c/li\u003e\n\u003cli\u003eGagelmann N, Kr\u0026ouml;ger N (2021) Dose intensity for conditioning in allogeneic hematopoietic cell transplantation: can we recommend \u0026ldquo;when and for whom\u0026rdquo; in 2021? Haematologica 106:1794\u0026ndash;1804. https://doi.org/10.3324/haematol.2020.268839\u003c/li\u003e\n\u003cli\u003eSengsayadeth S, Savani BN, Blaise D, et al (2015) Reduced intensity conditioning allogeneic hematopoietic cell transplantation for adult acute myeloid leukemia in complete remission - a review from the Acute Leukemia Working Party of the EBMT. Haematologica 100:859\u0026ndash;69. https://doi.org/10.3324/haematol.2015.123331\u003c/li\u003e\n\u003cli\u003eRussell JA, Tran HT, Quinlan D, et al (2002) Once-daily intravenous busulfan given with fludarabine as conditioning for allogeneic stem cell transplantation: study of pharmacokinetics and early clinical outcomes. Biol Blood Marrow Transplant 8:468\u0026ndash;76. https://doi.org/10.1053/bbmt.2002.v8.pm12374451\u003c/li\u003e\n\u003cli\u003eRambaldi A, Grassi A, Masciulli A, et al (2015) Busulfan plus cyclophosphamide versus busulfan plus fludarabine as a preparative regimen for allogeneic haemopoietic stem-cell transplantation in patients with acute myeloid leukaemia: an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol 16:1525\u0026ndash;1536. https://doi.org/10.1016/S1470-2045(15)00200-4\u003c/li\u003e\n\u003cli\u003eHolter-Chakrabarty JL, Pierson N, Zhang M-J, et al (2015) The Sequence of Cyclophosphamide and Myeloablative Total Body Irradiation in Hematopoietic Cell Transplantation for Patients with Acute Leukemia. Biol Blood Marrow Transplant 21:1251\u0026ndash;7. https://doi.org/10.1016/j.bbmt.2015.03.017\u003c/li\u003e\n\u003cli\u003eAtsuta Y, Suzuki R, Yoshimi A, et al (2007) Unification of hematopoietic stem cell transplantation registries in Japan and establishment of the TRUMP System. Int J Hematol 86:269\u0026ndash;74. https://doi.org/10.1532/IJH97.06239\u003c/li\u003e\n\u003cli\u003eAtsuta Y (2016) Introduction of Transplant Registry Unified Management Program 2 (TRUMP2): scripts for TRUMP data analyses, part I (variables other than HLA-related data). Int J Hematol 103:3\u0026ndash;10. https://doi.org/10.1007/s12185-015-1894-x\u003c/li\u003e\n\u003cli\u003eKanda J (2016) Scripts for TRUMP data analyses. Part II (HLA-related data): statistical analyses specific for hematopoietic stem cell transplantation. Int J Hematol 103:11\u0026ndash;9. https://doi.org/10.1007/s12185-015-1907-9\u003c/li\u003e\n\u003cli\u003ePrzepiorka D, Weisdorf D, Martin P, et al (1995) 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant 15:825\u0026ndash;8\u003c/li\u003e\n\u003cli\u003eShulman HM, Sullivan KM, Weiden PL, et al (1980) Chronic graft-versus-host syndrome in man. A long-term clinicopathologic study of 20 Seattle patients. Am J Med 69:204\u0026ndash;17\u003c/li\u003e\n\u003cli\u003eGratwohl a (2012) The EBMT risk score. Bone Marrow Transplant 47:749\u0026ndash;756. https://doi.org/10.1038/bmt.2011.110\u003c/li\u003e\n\u003cli\u003eSorror ML, Maris MB, Storb R, et al (2005) Hematopoietic cell transplantation (HCT)-specific comorbidity index: A new tool for risk assessment before allogeneic HCT. Blood 106:2912\u0026ndash;2919. https://doi.org/10.1182/blood-2005-05-2004\u003c/li\u003e\n\u003cli\u003eOken MM, Creech RH, Tormey DC, et al (1982) Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 5:649\u0026ndash;55\u003c/li\u003e\n\u003cli\u003eMcDonald GB, Hinds MS, Fisher LD, et al (1993) Veno-occlusive disease of the liver and multiorgan failure after bone marrow transplantation: a cohort study of 355 patients. Ann Intern Med 118:255\u0026ndash;67. https://doi.org/10.7326/0003-4819-118-4-199302150-00003\u003c/li\u003e\n\u003cli\u003eJones RJ, Lee KS, Beschorner WE, et al (1987) Venoocclusive disease of the liver following bone marrow transplantation. Transplantation 44:778\u0026ndash;83. https://doi.org/10.1097/00007890-198712000-00011\u003c/li\u003e\n\u003cli\u003eKaplan EL, Meier P (1958) Nonparametric Estimation from Incomplete Observations. J Am Stat Assoc 53:457\u0026ndash;581\u003c/li\u003e\n\u003cli\u003eGray RJ (1988) A Class of K-Sample Tests for Comparing the Cumulative Incidence of a Competing Risk. The Annals of Statistics 16:1141\u0026ndash;1154\u003c/li\u003e\n\u003cli\u003eFine JP, Gray RJ (1999) A Proportional Hazards Model for the Subdistribution of a Competing Risk. J Am Stat Assoc 94:496\u0026ndash;509\u003c/li\u003e\n\u003cli\u003eKanda Y (2013) Investigation of the freely available easy-to-use software \u0026ldquo;EZR\u0026rdquo; for medical statistics. Bone Marrow Transplant 48:452\u0026ndash;8. https://doi.org/10.1038/bmt.2012.244\u003c/li\u003e\n\u003cli\u003eGratwohl A, Hermans J, Goldman JM, et al (1998) Risk assessment for patients with chronic myeloid leukaemia before allogeneic blood or marrow transplantation. Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation. Lancet 352:1087\u0026ndash;92. https://doi.org/10.1016/s0140-6736(98)03030-x\u003c/li\u003e\n\u003cli\u003eClift RA, Buckner CD, Thomas ED, et al (1994) Marrow transplantation for chronic myeloid leukemia: a randomized study comparing cyclophosphamide and total body irradiation with busulfan and cyclophosphamide. Blood 84:2036\u0026ndash;43\u003c/li\u003e\n\u003cli\u003eTutschka PJ, Copelan EA, Kapoor N (1989) Replacing total body irradiation with busulfan as conditioning of patients with leukemia for allogeneic marrow transplantation. Transplant Proc 21:2952\u0026ndash;4\u003c/li\u003e\n\u003cli\u003eBlaise D, Maraninchi D, Archimbaud E, et al (1992) Allogeneic bone marrow transplantation for acute myeloid leukemia in first remission: a randomized trial of a busulfan-Cytoxan versus Cytoxan-total body irradiation as preparative regimen: a report from the Group d\u0026rsquo;Etudes de la Greffe de Moelle Osseuse. Blood 79:2578\u0026ndash;82\u003c/li\u003e\n\u003cli\u003eBredeson C, Lerademacher J, Kato K, et al (2013) Prospective cohort study comparing intravenous busulfan to total body irradiation in hematopoietic cell transplantation.\u003c/li\u003e\n\u003cli\u003ede Lima M, Couriel D, Thall PF, et al (2004) Once-daily intravenous busulfan and fludarabine: clinical and pharmacokinetic results of a myeloablative, reduced-toxicity conditioning regimen for allogeneic stem cell transplantation in AML and MDS. Blood 104:857\u0026ndash;64. https://doi.org/10.1182/blood-2004-02-0414\u003c/li\u003e\n\u003cli\u003eMagenau JM, Braun T, Reddy P, et al (2015) Allogeneic transplantation with myeloablative FluBu4 conditioning improves survival compared to reduced intensity FluBu2 conditioning for acute myeloid leukemia in remission. Ann Hematol 94:1033\u0026ndash;1041. https://doi.org/10.1007/s00277-015-2349-4\u003c/li\u003e\n\u003cli\u003eCorbacioglu S, Jabbour EJ, Mohty M (2019) Risk Factors for Development of and Progression of Hepatic Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome. Biol Blood Marrow Transplant 25:1271\u0026ndash;1280. https://doi.org/10.1016/j.bbmt.2019.02.018\u003c/li\u003e\n\u003cli\u003eShah NN, Hamadani M (2021) Is There Still a Role for Allogeneic Transplantation in the Management of Lymphoma? J Clin Oncol 39:487\u0026ndash;498. https://doi.org/10.1200/JCO.20.01447\u003c/li\u003e\n\u003cli\u003eNakane T, Fukuda T, Kanda J, et al (2015) Age influences post-graft-versus-host disease non-relapse mortality in adults with acute graft-versus-host disease of varying severity following allogeneic hematopoietic cell transplant. Leuk Lymphoma 56:2392\u0026ndash;7. https://doi.org/10.3109/10428194.2015.1009056\u003c/li\u003e\n\u003cli\u003eAndersson BS, Thall PF, Valdez BC, et al (2017) Fludarabine with pharmacokinetically guided IV busulfan is superior to fixed-dose delivery in pretransplant conditioning of AML/MDS patients. Bone Marrow Transplant 52:580\u0026ndash;587. https://doi.org/10.1038/bmt.2016.322\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1. Patients\u0026rsquo; background\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"642\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.51401869158879%\" colspan=\"2\"\u003e\n \u003cp\u003ePatients\u0026rsquo; group\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.102803738317757%\" colspan=\"2\"\u003e\n \u003cp\u003eYounger (\u0026lt;60 y/o)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.102803738317757%\" colspan=\"2\"\u003e\n \u003cp\u003eOlder (\u0026ge;60 y/o)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.280373831775702%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.45878693623639%\" colspan=\"2\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"13.063763608087092%\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.152410575427682%\"\u003e\n \u003cp\u003e%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.441679626749611%\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.618973561430794%\"\u003e\n \u003cp\u003e%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.26438569206843%\"\u003e\n \u003cp\u003eP-value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.45878693623639%\" colspan=\"2\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.063763608087092%\"\u003e\n \u003cp\u003e1,295\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.152410575427682%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"12.441679626749611%\"\u003e\n \u003cp\u003e993\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.618973561430794%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.26438569206843%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.573872472783826%\" rowspan=\"2\"\u003e\n \u003cp\u003eAge (y/o)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.884914463452567%\"\u003e\n \u003cp\u003eMean\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.063763608087092%\"\u003e\n \u003cp\u003e49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.152410575427682%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"12.441679626749611%\"\u003e\n \u003cp\u003e63.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.618973561430794%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.26438569206843%\" rowspan=\"2\"\u003e\n \u003cp\u003e\u0026lt;0.01*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.78448275862069%\"\u003e\n \u003cp\u003eMedian (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.103448275862068%\"\u003e\n \u003cp\u003e53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.612068965517242%\"\u003e\n \u003cp\u003e16\u0026ndash;59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.24137931034483%\"\u003e\n \u003cp\u003e63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.25862068965517%\"\u003e\n \u003cp\u003e60\u0026ndash;80\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.573872472783826%\" rowspan=\"2\"\u003e\n \u003cp\u003eSex\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.884914463452567%\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.063763608087092%\"\u003e\n \u003cp\u003e519\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.152410575427682%\"\u003e\n \u003cp\u003e40.1%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.441679626749611%\"\u003e\n \u003cp\u003e336\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.618973561430794%\"\u003e\n \u003cp\u003e33.8%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.26438569206843%\" rowspan=\"2\"\u003e\n \u003cp\u003e\u0026lt;0.01*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.78448275862069%\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.103448275862068%\"\u003e\n \u003cp\u003e776\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.612068965517242%\"\u003e\n \u003cp\u003e59.9%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.24137931034483%\"\u003e\n \u003cp\u003e657\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.25862068965517%\"\u003e\n \u003cp\u003e66.2%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.573872472783826%\" rowspan=\"8\"\u003e\n \u003cp\u003eDiagnosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.884914463452567%\"\u003e\n \u003cp\u003eAML\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.063763608087092%\"\u003e\n \u003cp\u003e731\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.152410575427682%\"\u003e\n \u003cp\u003e56.4%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.441679626749611%\"\u003e\n \u003cp\u003e564\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.618973561430794%\"\u003e\n \u003cp\u003e56.8%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.26438569206843%\" rowspan=\"8\"\u003e\n \u003cp\u003e\u0026lt;0.01*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.78448275862069%\"\u003e\n \u003cp\u003eALL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.103448275862068%\"\u003e\n \u003cp\u003e54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.612068965517242%\"\u003e\n \u003cp\u003e4.2%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.24137931034483%\"\u003e\n \u003cp\u003e35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.25862068965517%\"\u003e\n \u003cp\u003e3.5%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.78448275862069%\"\u003e\n \u003cp\u003eOther AL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.103448275862068%\"\u003e\n \u003cp\u003e43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.612068965517242%\"\u003e\n \u003cp\u003e3.3%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.24137931034483%\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.25862068965517%\"\u003e\n \u003cp\u003e2.6%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.78448275862069%\"\u003e\n \u003cp\u003eMDS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.103448275862068%\"\u003e\n \u003cp\u003e287\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.612068965517242%\"\u003e\n \u003cp\u003e22.2%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.24137931034483%\"\u003e\n \u003cp\u003e285\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.25862068965517%\"\u003e\n \u003cp\u003e28.7%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.78448275862069%\"\u003e\n \u003cp\u003eCML\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.103448275862068%\"\u003e\n \u003cp\u003e42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.612068965517242%\"\u003e\n \u003cp\u003e3.2%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.24137931034483%\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.25862068965517%\"\u003e\n \u003cp\u003e2.4%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.78448275862069%\"\u003e\n \u003cp\u003eMPN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.103448275862068%\"\u003e\n \u003cp\u003e31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.612068965517242%\"\u003e\n \u003cp\u003e2.4%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.24137931034483%\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.25862068965517%\"\u003e\n \u003cp\u003e2.8%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.78448275862069%\"\u003e\n \u003cp\u003eLymphoma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.103448275862068%\"\u003e\n \u003cp\u003e102\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.612068965517242%\"\u003e\n \u003cp\u003e7.9%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.24137931034483%\"\u003e\n \u003cp\u003e31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.25862068965517%\"\u003e\n \u003cp\u003e3.1%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.78448275862069%\"\u003e\n \u003cp\u003eMM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.103448275862068%\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.612068965517242%\"\u003e\n \u003cp\u003e0.4%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.24137931034483%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.25862068965517%\"\u003e\n \u003cp\u003e0.0%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.573872472783826%\" rowspan=\"3\"\u003e\n \u003cp\u003eDisease status at HSCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.884914463452567%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.063763608087092%\"\u003e\n \u003cp\u003e579\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.152410575427682%\"\u003e\n \u003cp\u003e44.7%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.441679626749611%\"\u003e\n \u003cp\u003e403\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.618973561430794%\"\u003e\n \u003cp\u003e40.6%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.26438569206843%\" rowspan=\"3\"\u003e\n \u003cp\u003e0.10\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.78448275862069%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.103448275862068%\"\u003e\n \u003cp\u003e242\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.612068965517242%\"\u003e\n \u003cp\u003e18.7%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.24137931034483%\"\u003e\n \u003cp\u003e213\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.25862068965517%\"\u003e\n \u003cp\u003e21.5%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.78448275862069%\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.103448275862068%\"\u003e\n \u003cp\u003e474\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.612068965517242%\"\u003e\n \u003cp\u003e36.6%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.24137931034483%\"\u003e\n \u003cp\u003e377\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.25862068965517%\"\u003e\n \u003cp\u003e38.0%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.573872472783826%\" rowspan=\"2\"\u003e\n \u003cp\u003eCell source\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.884914463452567%\"\u003e\n \u003cp\u003eBM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.063763608087092%\"\u003e\n \u003cp\u003e791\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.152410575427682%\"\u003e\n \u003cp\u003e61.1%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.441679626749611%\"\u003e\n \u003cp\u003e728\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.618973561430794%\"\u003e\n \u003cp\u003e73.3%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.26438569206843%\" rowspan=\"2\"\u003e\n \u003cp\u003e\u0026lt;0.01*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.78448275862069%\"\u003e\n \u003cp\u003ePB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.103448275862068%\"\u003e\n \u003cp\u003e504\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.612068965517242%\"\u003e\n \u003cp\u003e38.9%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.24137931034483%\"\u003e\n \u003cp\u003e265\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.25862068965517%\"\u003e\n \u003cp\u003e26.7%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.573872472783826%\" rowspan=\"2\"\u003e\n \u003cp\u003eDonor type\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.884914463452567%\"\u003e\n \u003cp\u003eMRD/MUD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.063763608087092%\"\u003e\n \u003cp\u003e774\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.152410575427682%\"\u003e\n \u003cp\u003e59.8%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.441679626749611%\"\u003e\n \u003cp\u003e640\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.618973561430794%\"\u003e\n \u003cp\u003e64.5%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.26438569206843%\" rowspan=\"2\"\u003e\n \u003cp\u003e0.02*\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.78448275862069%\"\u003e\n \u003cp\u003eOthers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.103448275862068%\"\u003e\n \u003cp\u003e521\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.612068965517242%\"\u003e\n \u003cp\u003e40.2%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.24137931034483%\"\u003e\n \u003cp\u003e353\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.25862068965517%\"\u003e\n \u003cp\u003e35.5%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.573872472783826%\" rowspan=\"2\"\u003e\n \u003cp\u003eSex comb.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.884914463452567%\"\u003e\n \u003cp\u003eF to M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.063763608087092%\"\u003e\n \u003cp\u003e1,018\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.152410575427682%\"\u003e\n \u003cp\u003e78.6%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.441679626749611%\"\u003e\n \u003cp\u003e782\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.618973561430794%\"\u003e\n \u003cp\u003e78.8%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.26438569206843%\" rowspan=\"2\"\u003e\n \u003cp\u003e0.93\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.78448275862069%\"\u003e\n \u003cp\u003eOthers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.103448275862068%\"\u003e\n \u003cp\u003e277\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.612068965517242%\"\u003e\n \u003cp\u003e21.4%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.24137931034483%\"\u003e\n \u003cp\u003e211\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.25862068965517%\"\u003e\n \u003cp\u003e21.2%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.573872472783826%\" rowspan=\"5\"\u003e\n \u003cp\u003eDx to HSCT\u003c/p\u003e\n \u003cp\u003e(day)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.884914463452567%\"\u003e\n \u003cp\u003eMedian (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.063763608087092%\"\u003e\n \u003cp\u003e234\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.152410575427682%\"\u003e\n \u003cp\u003e157\u0026ndash;497\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.441679626749611%\"\u003e\n \u003cp\u003e221.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.618973561430794%\"\u003e\n \u003cp\u003e163.5\u0026ndash;433\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.26438569206843%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"21.69811320754717%\"\u003e\n \u003cp\u003e\u0026lt;=90\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.849056603773585%\"\u003e\n \u003cp\u003e82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.169811320754718%\"\u003e\n \u003cp\u003e6.3%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.09433962264151%\"\u003e\n \u003cp\u003e63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.735849056603772%\"\u003e\n \u003cp\u003e6.3%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.452830188679245%\" rowspan=\"4\"\u003e\n \u003cp\u003e0.68\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.78448275862069%\"\u003e\n \u003cp\u003e90\u0026ndash;180\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.103448275862068%\"\u003e\n \u003cp\u003e367\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.612068965517242%\"\u003e\n \u003cp\u003e28.3%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.24137931034483%\"\u003e\n \u003cp\u003e259\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.25862068965517%\"\u003e\n \u003cp\u003e26.1%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.78448275862069%\"\u003e\n \u003cp\u003e\u0026gt;180\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.103448275862068%\"\u003e\n \u003cp\u003e845\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.612068965517242%\"\u003e\n \u003cp\u003e65.3%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.24137931034483%\"\u003e\n \u003cp\u003e670\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.25862068965517%\"\u003e\n \u003cp\u003e67.5%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.78448275862069%\"\u003e\n \u003cp\u003eMissing\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.103448275862068%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.612068965517242%\"\u003e\n \u003cp\u003e0.1%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.24137931034483%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.25862068965517%\"\u003e\n \u003cp\u003e0.1%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.573872472783826%\" rowspan=\"5\"\u003e\n \u003cp\u003eABO\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.884914463452567%\"\u003e\n \u003cp\u003eMajor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.063763608087092%\"\u003e\n \u003cp\u003e222\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.152410575427682%\"\u003e\n \u003cp\u003e17.1%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.441679626749611%\"\u003e\n \u003cp\u003e180\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.618973561430794%\"\u003e\n \u003cp\u003e18.1%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.26438569206843%\" rowspan=\"5\"\u003e\n \u003cp\u003e0.59\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.78448275862069%\"\u003e\n \u003cp\u003eBidirectional\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.103448275862068%\"\u003e\n \u003cp\u003e105\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.612068965517242%\"\u003e\n \u003cp\u003e8.1%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.24137931034483%\"\u003e\n \u003cp\u003e92\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.25862068965517%\"\u003e\n \u003cp\u003e9.3%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.78448275862069%\"\u003e\n \u003cp\u003eMinor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.103448275862068%\"\u003e\n \u003cp\u003e250\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.612068965517242%\"\u003e\n \u003cp\u003e19.3%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.24137931034483%\"\u003e\n \u003cp\u003e174\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.25862068965517%\"\u003e\n \u003cp\u003e17.5%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.78448275862069%\"\u003e\n \u003cp\u003eMatch\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.103448275862068%\"\u003e\n \u003cp\u003e717\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.612068965517242%\"\u003e\n \u003cp\u003e55.4%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.24137931034483%\"\u003e\n \u003cp\u003e545\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.25862068965517%\"\u003e\n \u003cp\u003e54.9%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.78448275862069%\"\u003e\n \u003cp\u003eMissing\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.103448275862068%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.612068965517242%\"\u003e\n \u003cp\u003e0.1%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.24137931034483%\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.25862068965517%\"\u003e\n \u003cp\u003e0.2%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.573872472783826%\" rowspan=\"2\"\u003e\n \u003cp\u003eUse of ATG/ALG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.884914463452567%\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.063763608087092%\"\u003e\n \u003cp\u003e1,109\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.152410575427682%\"\u003e\n \u003cp\u003e85.6%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.441679626749611%\"\u003e\n \u003cp\u003e869\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.618973561430794%\"\u003e\n \u003cp\u003e87.5%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.26438569206843%\" rowspan=\"2\"\u003e\n \u003cp\u003e0.19\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.78448275862069%\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.103448275862068%\"\u003e\n \u003cp\u003e186\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.612068965517242%\"\u003e\n \u003cp\u003e14.4%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.24137931034483%\"\u003e\n \u003cp\u003e124\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.25862068965517%\"\u003e\n \u003cp\u003e12.5%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.573872472783826%\" rowspan=\"2\"\u003e\n \u003cp\u003eTBI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.884914463452567%\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.063763608087092%\"\u003e\n \u003cp\u003e776\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.152410575427682%\"\u003e\n \u003cp\u003e59.9%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.441679626749611%\"\u003e\n \u003cp\u003e554\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.618973561430794%\"\u003e\n \u003cp\u003e55.8%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.26438569206843%\" rowspan=\"2\"\u003e\n \u003cp\u003e0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.78448275862069%\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.103448275862068%\"\u003e\n \u003cp\u003e519\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.612068965517242%\"\u003e\n \u003cp\u003e40.1%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.24137931034483%\"\u003e\n \u003cp\u003e439\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.25862068965517%\"\u003e\n \u003cp\u003e44.2%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.573872472783826%\" rowspan=\"2\"\u003e\n \u003cp\u003eAdd. chem. drug\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.884914463452567%\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.063763608087092%\"\u003e\n \u003cp\u003e1,013\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.152410575427682%\"\u003e\n \u003cp\u003e78.2%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.441679626749611%\"\u003e\n \u003cp\u003e870\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.618973561430794%\"\u003e\n \u003cp\u003e87.6%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.26438569206843%\" rowspan=\"2\"\u003e\n \u003cp\u003e\u0026lt;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.78448275862069%\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.103448275862068%\"\u003e\n \u003cp\u003e282\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.612068965517242%\"\u003e\n \u003cp\u003e21.8%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.24137931034483%\"\u003e\n \u003cp\u003e123\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.25862068965517%\"\u003e\n \u003cp\u003e12.4%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.573872472783826%\" rowspan=\"3\"\u003e\n \u003cp\u003ePerformance status\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.884914463452567%\"\u003e\n \u003cp\u003e0\u0026ndash;1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.063763608087092%\"\u003e\n \u003cp\u003e1,183\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.152410575427682%\"\u003e\n \u003cp\u003e91.4%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.441679626749611%\"\u003e\n \u003cp\u003e885\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.618973561430794%\"\u003e\n \u003cp\u003e89.1%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.26438569206843%\" rowspan=\"3\"\u003e\n \u003cp\u003e0.20\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.78448275862069%\"\u003e\n \u003cp\u003e2\u0026ndash;4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.103448275862068%\"\u003e\n \u003cp\u003e111\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.612068965517242%\"\u003e\n \u003cp\u003e8.6%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.24137931034483%\"\u003e\n \u003cp\u003e107\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.25862068965517%\"\u003e\n \u003cp\u003e10.8%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.78448275862069%\"\u003e\n \u003cp\u003eMissing\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.103448275862068%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.612068965517242%\"\u003e\n \u003cp\u003e0.1%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.24137931034483%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.25862068965517%\"\u003e\n \u003cp\u003e0.1%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.573872472783826%\" rowspan=\"2\"\u003e\n \u003cp\u003eHCT-CI score\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.884914463452567%\"\u003e\n \u003cp\u003e0\u0026ndash;2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.063763608087092%\"\u003e\n \u003cp\u003e1,029\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.152410575427682%\"\u003e\n \u003cp\u003e79.5%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.441679626749611%\"\u003e\n \u003cp\u003e788\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.618973561430794%\"\u003e\n \u003cp\u003e79.4%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.26438569206843%\" rowspan=\"2\"\u003e\n \u003cp\u003e0.95\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.78448275862069%\"\u003e\n \u003cp\u003e\u0026ge;3\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.103448275862068%\"\u003e\n \u003cp\u003e266\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.612068965517242%\"\u003e\n \u003cp\u003e20.5%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.24137931034483%\"\u003e\n \u003cp\u003e205\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.25862068965517%\"\u003e\n \u003cp\u003e20.6%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.573872472783826%\" rowspan=\"3\"\u003e\n \u003cp\u003eCMV risk\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.884914463452567%\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.063763608087092%\"\u003e\n \u003cp\u003e91\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.152410575427682%\"\u003e\n \u003cp\u003e7.0%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.441679626749611%\"\u003e\n \u003cp\u003e61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.618973561430794%\"\u003e\n \u003cp\u003e6.1%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.26438569206843%\" rowspan=\"3\"\u003e\n \u003cp\u003e0.45\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.78448275862069%\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.103448275862068%\"\u003e\n \u003cp\u003e1,146\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.612068965517242%\"\u003e\n \u003cp\u003e88.5%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.24137931034483%\"\u003e\n \u003cp\u003e895\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.25862068965517%\"\u003e\n \u003cp\u003e90.1%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.78448275862069%\"\u003e\n \u003cp\u003eMissing\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.103448275862068%\"\u003e\n \u003cp\u003e58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.612068965517242%\"\u003e\n \u003cp\u003e4.5%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.24137931034483%\"\u003e\n \u003cp\u003e37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.25862068965517%\"\u003e\n \u003cp\u003e3.7%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.573872472783826%\" rowspan=\"2\"\u003e\n \u003cp\u003eHSCT year\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.884914463452567%\"\u003e\n \u003cp\u003eBefore 2013\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.063763608087092%\"\u003e\n \u003cp\u003e435\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.152410575427682%\"\u003e\n \u003cp\u003e33.6%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.441679626749611%\"\u003e\n \u003cp\u003e300\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.618973561430794%\"\u003e\n \u003cp\u003e30.2%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.26438569206843%\" rowspan=\"2\"\u003e\n \u003cp\u003e0.09\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.78448275862069%\"\u003e\n \u003cp\u003e2013 or later\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.103448275862068%\"\u003e\n \u003cp\u003e860\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.612068965517242%\"\u003e\n \u003cp\u003e66.4%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.24137931034483%\"\u003e\n \u003cp\u003e693\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.25862068965517%\"\u003e\n \u003cp\u003e69.8%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eABO, ABO blood group mismatch pattern between the donor and the recipient; Add. chem. drug, additional chemotherapeutic drug; ALG, anti-lymphocyte globulin; ALL, acute lymphoblastic leukemia; AML, acute myeloid leukemia; ATG, anti-thymocyte globulin; BM, bone marrow; CML, chronic myeloid leukemia; CMV, cytomegalovirus; comb., combination; Disease stage, categorized according to EBMT risk score [20]; Dx, diagnosis; F to M, HSCT from female donor to male recipient; HCT-CI, hematopoietic cell transplantation-specific comorbidity index; HSCT, hematopoietic stem cell transplantation; MDS, myelodysplastic syndrome; MM, multiple myeloma; MPN, myeloproliferative neoplasm; MRD, matched-related donor; MUD, matched-unrelated donor; Other AL, other types of acute leukemia; PB, peripheral blood; TBI, total body irradiation; y/o, years old; *, significant difference (p\u0026lt;0.05)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2a. Multivariate analysis for OS\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"641\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.71762870514821%\" colspan=\"2\" rowspan=\"2\"\u003e\n \u003cp\u003eFactor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.820592823712948%\" rowspan=\"2\"\u003e\n \u003cp\u003eHR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.641185647425896%\" colspan=\"2\"\u003e\n \u003cp\u003e95% CI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.820592823712948%\" rowspan=\"2\"\u003e\n \u003cp\u003eP-value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50.261780104712045%\"\u003e\n \u003cp\u003eLower\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"49.738219895287955%\"\u003e\n \u003cp\u003eUpper\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.5202492211838%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.133956386292834%\"\u003e\n \u003cp\u003e\u0026lt;60 y/o\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.797507788161994%\"\u003e\n \u003cp\u003eRef.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.953271028037383%\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.797507788161994%\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.797507788161994%\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.403258655804482%\"\u003e\n \u003cp\u003e\u0026ge;60 y/o\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.34826883910387%\"\u003e\n \u003cp\u003e1.35\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.55193482688391%\"\u003e\n \u003cp\u003e1.20\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.34826883910387%\"\u003e\n \u003cp\u003e1.51\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.34826883910387%\"\u003e\n \u003cp\u003e\u0026lt;0.01*\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.5202492211838%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eDisease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.133956386292834%\"\u003e\n \u003cp\u003eMyeloid\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.797507788161994%\"\u003e\n \u003cp\u003eRef.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.953271028037383%\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.797507788161994%\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.797507788161994%\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.403258655804482%\"\u003e\n \u003cp\u003eOthers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.34826883910387%\"\u003e\n \u003cp\u003e1.45\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.55193482688391%\"\u003e\n \u003cp\u003e1.24\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.34826883910387%\"\u003e\n \u003cp\u003e1.70\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.34826883910387%\"\u003e\n \u003cp\u003e\u0026lt;0.01*\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.5202492211838%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eDx to HSCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.133956386292834%\"\u003e\n \u003cp\u003e\u0026lt;1 y\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.797507788161994%\"\u003e\n \u003cp\u003eRef.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.953271028037383%\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.797507788161994%\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.797507788161994%\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.403258655804482%\"\u003e\n \u003cp\u003e\u0026gt;1 y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.34826883910387%\"\u003e\n \u003cp\u003e0.82\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.55193482688391%\"\u003e\n \u003cp\u003e0.72\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.34826883910387%\"\u003e\n \u003cp\u003e0.94\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.34826883910387%\"\u003e\n \u003cp\u003e\u0026lt;0.01*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.5202492211838%\" rowspan=\"3\" valign=\"top\"\u003e\n \u003cp\u003eDisease stage at HSCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.133956386292834%\"\u003e\n \u003cp\u003eEarly\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.797507788161994%\"\u003e\n \u003cp\u003eRef.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.953271028037383%\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.797507788161994%\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.797507788161994%\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.403258655804482%\"\u003e\n \u003cp\u003eIntermediate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.34826883910387%\"\u003e\n \u003cp\u003e1.09\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.55193482688391%\"\u003e\n \u003cp\u003e0.91\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.34826883910387%\"\u003e\n \u003cp\u003e1.31\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.34826883910387%\"\u003e\n \u003cp\u003e0.36\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.403258655804482%\"\u003e\n \u003cp\u003eLate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.34826883910387%\"\u003e\n \u003cp\u003e2.12\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.55193482688391%\"\u003e\n \u003cp\u003e1.85\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.34826883910387%\"\u003e\n \u003cp\u003e2.42\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.34826883910387%\"\u003e\n \u003cp\u003e\u0026lt;0.01*\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.5202492211838%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eDonor type\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.133956386292834%\"\u003e\n \u003cp\u003eMRD or MUD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.797507788161994%\"\u003e\n \u003cp\u003eRef.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.953271028037383%\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.797507788161994%\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.797507788161994%\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.403258655804482%\"\u003e\n \u003cp\u003eOthers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.34826883910387%\"\u003e\n \u003cp\u003e1.17\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.55193482688391%\"\u003e\n \u003cp\u003e1.04\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.34826883910387%\"\u003e\n \u003cp\u003e1.31\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.34826883910387%\"\u003e\n \u003cp\u003e0.01*\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.5202492211838%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eF to M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.133956386292834%\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.797507788161994%\"\u003e\n \u003cp\u003eRef.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.953271028037383%\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.797507788161994%\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.797507788161994%\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.403258655804482%\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.34826883910387%\"\u003e\n \u003cp\u003e1.15\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.55193482688391%\"\u003e\n \u003cp\u003e1.00\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.34826883910387%\"\u003e\n \u003cp\u003e1.32\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.34826883910387%\"\u003e\n \u003cp\u003e0.04*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.5202492211838%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003ePerformance status\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.133956386292834%\"\u003e\n \u003cp\u003e0\u0026ndash;1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.797507788161994%\"\u003e\n \u003cp\u003eRef.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.953271028037383%\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.797507788161994%\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.797507788161994%\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.403258655804482%\"\u003e\n \u003cp\u003e2\u0026ndash;4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.34826883910387%\"\u003e\n \u003cp\u003e2.21\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.55193482688391%\"\u003e\n \u003cp\u003e1.87\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.34826883910387%\"\u003e\n \u003cp\u003e2.62\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.34826883910387%\"\u003e\n \u003cp\u003e\u0026lt;0.01*\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.5202492211838%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eHCT-CI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.133956386292834%\"\u003e\n \u003cp\u003e0\u0026ndash;2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.797507788161994%\"\u003e\n \u003cp\u003eRef.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.953271028037383%\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.797507788161994%\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.797507788161994%\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.403258655804482%\"\u003e\n \u003cp\u003e\u0026ge;3\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.34826883910387%\"\u003e\n \u003cp\u003e1.07\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.55193482688391%\"\u003e\n \u003cp\u003e0.93\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.34826883910387%\"\u003e\n \u003cp\u003e1.23\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.34826883910387%\"\u003e\n \u003cp\u003e0.35\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eCI, confidence interval; Disease stage, categorized according to EBMT risk score [20]; wDx, diagnosis; F to M, HSCT from female donor to male recipient; HCT-CI, hematopoietic cell transplantation-specific comorbidity index; HR, hazard ratio; HSCT, hematopoietic stem cell transplantation; MRD, matched-related donor; MUD, matched-unrelated donor; OS, overall survival; Ref., reference; y/o, years old; *, significant difference (p\u0026lt;0.05)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2b. Multivariate analysis for NRM\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"643\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"41.05754276827372%\" colspan=\"2\" rowspan=\"2\"\u003e\n \u003cp\u003eFactor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.774494556765163%\" rowspan=\"2\"\u003e\n \u003cp\u003eHR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.393468118195955%\" colspan=\"2\"\u003e\n \u003cp\u003e95% CI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.774494556765163%\" rowspan=\"2\"\u003e\n \u003cp\u003eP-value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"49.735449735449734%\"\u003e\n \u003cp\u003eLower\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50.264550264550266%\"\u003e\n \u003cp\u003eUpper\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.48367029548989%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.573872472783826%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;60 y/o\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.774494556765163%\" valign=\"top\"\u003e\n \u003cp\u003eRef.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.618973561430794%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.774494556765163%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.774494556765163%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.96747967479675%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026ge;60 y/o\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.308943089430894%\" valign=\"top\"\u003e\n \u003cp\u003e1.41\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.10569105691057%\" valign=\"top\"\u003e\n \u003cp\u003e1.20\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.308943089430894%\" valign=\"top\"\u003e\n \u003cp\u003e1.67\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.308943089430894%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.01*\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.48367029548989%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eDisease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.573872472783826%\" valign=\"top\"\u003e\n \u003cp\u003eMyeloid\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.774494556765163%\" valign=\"top\"\u003e\n \u003cp\u003eRef.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.618973561430794%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.774494556765163%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.774494556765163%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.96747967479675%\" valign=\"top\"\u003e\n \u003cp\u003eOthers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.308943089430894%\" valign=\"top\"\u003e\n \u003cp\u003e1.30\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.10569105691057%\" valign=\"top\"\u003e\n \u003cp\u003e1.03\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.308943089430894%\" valign=\"top\"\u003e\n \u003cp\u003e1.63\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.308943089430894%\" valign=\"top\"\u003e\n \u003cp\u003e0.03*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.48367029548989%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eDx to HSCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.573872472783826%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;1 year\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.774494556765163%\" valign=\"top\"\u003e\n \u003cp\u003eRef.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.618973561430794%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.774494556765163%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.774494556765163%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.96747967479675%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026gt;1 year\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.308943089430894%\" valign=\"top\"\u003e\n \u003cp\u003e1.28\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.10569105691057%\" valign=\"top\"\u003e\n \u003cp\u003e1.08\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.308943089430894%\" valign=\"top\"\u003e\n \u003cp\u003e1.52\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.308943089430894%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.01*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.48367029548989%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eDonor type\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.573872472783826%\" valign=\"top\"\u003e\n \u003cp\u003eMRD or MUD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.774494556765163%\" valign=\"top\"\u003e\n \u003cp\u003eRef.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.618973561430794%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.774494556765163%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.774494556765163%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.96747967479675%\" valign=\"top\"\u003e\n \u003cp\u003eOthers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.308943089430894%\" valign=\"top\"\u003e\n \u003cp\u003e1.21\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.10569105691057%\" valign=\"top\"\u003e\n \u003cp\u003e1.02\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.308943089430894%\" valign=\"top\"\u003e\n \u003cp\u003e1.45\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.308943089430894%\" valign=\"top\"\u003e\n \u003cp\u003e0.03*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.48367029548989%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003ePerformance status\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.573872472783826%\" valign=\"top\"\u003e\n \u003cp\u003e0\u0026ndash;1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.774494556765163%\" valign=\"top\"\u003e\n \u003cp\u003eRef.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.618973561430794%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.774494556765163%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.774494556765163%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.96747967479675%\" valign=\"top\"\u003e\n \u003cp\u003e2\u0026ndash;4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.308943089430894%\" valign=\"top\"\u003e\n \u003cp\u003e1.44\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.10569105691057%\" valign=\"top\"\u003e\n \u003cp\u003e1.11\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.308943089430894%\" valign=\"top\"\u003e\n \u003cp\u003e1.87\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.308943089430894%\" valign=\"top\"\u003e\n \u003cp\u003e0.01*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.48367029548989%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eUse of ATG/ALG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.573872472783826%\" valign=\"top\"\u003e\n \u003cp\u003eNone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.774494556765163%\" valign=\"top\"\u003e\n \u003cp\u003eRef.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.618973561430794%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.774494556765163%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.774494556765163%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.96747967479675%\" valign=\"top\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.308943089430894%\" valign=\"top\"\u003e\n \u003cp\u003e0.72\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.10569105691057%\" valign=\"top\"\u003e\n \u003cp\u003e0.55\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.308943089430894%\" valign=\"top\"\u003e\n \u003cp\u003e0.94\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.308943089430894%\" valign=\"top\"\u003e\n \u003cp\u003e0.02*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.48367029548989%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eUse of TBI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.573872472783826%\" valign=\"top\"\u003e\n \u003cp\u003eNone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.774494556765163%\" valign=\"top\"\u003e\n \u003cp\u003eRef.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.618973561430794%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.774494556765163%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.774494556765163%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.96747967479675%\" valign=\"top\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.308943089430894%\" valign=\"top\"\u003e\n \u003cp\u003e1.23\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.10569105691057%\" valign=\"top\"\u003e\n \u003cp\u003e1.04\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.308943089430894%\" valign=\"top\"\u003e\n \u003cp\u003e1.45\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.308943089430894%\" valign=\"top\"\u003e\n \u003cp\u003e0.02*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eALG, anti-lymphocyte globulin; ATG, anti-thymocyte globulin; CI, confidence interval;\u0026nbsp;Dx, diagnosis;\u0026nbsp;HR, hazard ratio;\u0026nbsp;HSCT, hematopoietic stem cell transplantation;\u0026nbsp;MRD, matched-related donor; MUD, matched-unrelated donor; NRM, non-relapse mortality; Ref., reference; TBI, total body irradiation; y/o, years old; *, significant difference (p\u0026lt;0.05)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2c. Multivariate analysis for CIR\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"641\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"41.12149532710281%\" colspan=\"2\" rowspan=\"2\"\u003e\n \u003cp\u003eFactor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.797507788161994%\" rowspan=\"2\"\u003e\n \u003cp\u003eHR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.12772585669782%\" colspan=\"2\"\u003e\n \u003cp\u003e95% CI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.953271028037383%\" rowspan=\"2\"\u003e\n \u003cp\u003eP-value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"48.924731182795696%\"\u003e\n \u003cp\u003eLower\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"51.075268817204304%\"\u003e\n \u003cp\u003eUpper\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.556942277691107%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eDisease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.628705148205928%\"\u003e\n \u003cp\u003eMyeloid\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.820592823712948%\"\u003e\n \u003cp\u003eRef.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.196567862714508%\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.820592823712948%\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.976599063962558%\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.06122448979592%\"\u003e\n \u003cp\u003eOthers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\"\u003e\n \u003cp\u003e1.42\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.571428571428573%\"\u003e\n \u003cp\u003e1.16\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\"\u003e\n \u003cp\u003e1.74\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.591836734693878%\"\u003e\n \u003cp\u003e\u0026lt;0.01*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.556942277691107%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eDx to HSCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.628705148205928%\"\u003e\n \u003cp\u003e\u0026le;1 y\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.820592823712948%\"\u003e\n \u003cp\u003eRef.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.196567862714508%\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.820592823712948%\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.976599063962558%\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.06122448979592%\"\u003e\n \u003cp\u003e\u0026gt;1 y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\"\u003e\n \u003cp\u003e0.55\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.571428571428573%\"\u003e\n \u003cp\u003e0.46\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\"\u003e\n \u003cp\u003e0.66\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.591836734693878%\"\u003e\n \u003cp\u003e\u0026lt;0.01*\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.556942277691107%\" rowspan=\"3\" valign=\"top\"\u003e\n \u003cp\u003eDisease stage at HSCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.628705148205928%\"\u003e\n \u003cp\u003eEarly\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.820592823712948%\"\u003e\n \u003cp\u003eRef.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.196567862714508%\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.820592823712948%\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.976599063962558%\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.06122448979592%\"\u003e\n \u003cp\u003eIntermediate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\"\u003e\n \u003cp\u003e1.73\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.571428571428573%\"\u003e\n \u003cp\u003e1.36\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\"\u003e\n \u003cp\u003e2.19\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.591836734693878%\"\u003e\n \u003cp\u003e\u0026lt;0.01*\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.06122448979592%\"\u003e\n \u003cp\u003eLate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\"\u003e\n \u003cp\u003e3.09\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.571428571428573%\"\u003e\n \u003cp\u003e2.61\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\"\u003e\n \u003cp\u003e3.67\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.591836734693878%\"\u003e\n \u003cp\u003e\u0026lt;0.01*\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.556942277691107%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eCell source\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.628705148205928%\"\u003e\n \u003cp\u003eBM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.820592823712948%\"\u003e\n \u003cp\u003eRef.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.196567862714508%\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.820592823712948%\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.976599063962558%\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.06122448979592%\"\u003e\n \u003cp\u003ePB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\"\u003e\n \u003cp\u003e1.03\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.571428571428573%\"\u003e\n \u003cp\u003e0.88\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\"\u003e\n \u003cp\u003e1.20\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.591836734693878%\"\u003e\n \u003cp\u003e0.69\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.556942277691107%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003ePerformance status\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.628705148205928%\"\u003e\n \u003cp\u003e0\u0026ndash;1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.820592823712948%\"\u003e\n \u003cp\u003eRef.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.196567862714508%\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.820592823712948%\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.976599063962558%\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.06122448979592%\"\u003e\n \u003cp\u003e2\u0026ndash;4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\"\u003e\n \u003cp\u003e1.52\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.571428571428573%\"\u003e\n \u003cp\u003e1.23\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\"\u003e\n \u003cp\u003e1.88\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.591836734693878%\"\u003e\n \u003cp\u003e\u0026lt;0.01*\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.556942277691107%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eUse of TBI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.628705148205928%\"\u003e\n \u003cp\u003eNone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.820592823712948%\"\u003e\n \u003cp\u003eRef.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.196567862714508%\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.820592823712948%\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.976599063962558%\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.06122448979592%\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\"\u003e\n \u003cp\u003e0.84\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.571428571428573%\"\u003e\n \u003cp\u003e0.72\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\"\u003e\n \u003cp\u003e0.97\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.591836734693878%\"\u003e\n \u003cp\u003e0.02*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eBM, bone marrow; CI, confidence interval; CIR, cumulative incidence of relapse; Disease stage, categorized according to EBMT risk score [20]; Dx, diagnosis; HR, hazard ratio; HSCT, hematopoietic stem cell transplantation; PB, peripheral blood; Ref., reference; TBI, total body irradiation; *, significant difference (p\u0026lt;0.05)\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3. Causes of death\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"642\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"38.3177570093458%\" rowspan=\"2\"\u003e\n \u003cp\u003eCauses of death\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"61.6822429906542%\" colspan=\"4\"\u003e\n \u003cp\u003ePatients\u0026rsquo; group\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" colspan=\"2\"\u003e\n \u003cp\u003eYounger (\u0026lt;60 y/o)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" colspan=\"2\"\u003e\n \u003cp\u003eOlder (\u0026ge;60 y/o)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38.25816485225506%\"\u003e\n \u003cp\u003eRelapse\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.174183514774494%\"\u003e\n \u003cp\u003e281\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.774494556765163%\"\u003e\n \u003cp\u003e29.1%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.174183514774494%\"\u003e\n \u003cp\u003e242\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.618973561430794%\"\u003e\n \u003cp\u003e27.8%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38.25816485225506%\"\u003e\n \u003cp\u003eAcute GVHD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.174183514774494%\"\u003e\n \u003cp\u003e70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.774494556765163%\"\u003e\n \u003cp\u003e7.3%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.174183514774494%\"\u003e\n \u003cp\u003e65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.618973561430794%\"\u003e\n \u003cp\u003e7.5%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38.25816485225506%\"\u003e\n \u003cp\u003eChronic GVHD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.174183514774494%\"\u003e\n \u003cp\u003e55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.774494556765163%\"\u003e\n \u003cp\u003e5.7%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.174183514774494%\"\u003e\n \u003cp\u003e46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.618973561430794%\"\u003e\n \u003cp\u003e5.3%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38.25816485225506%\"\u003e\n \u003cp\u003eRejection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.174183514774494%\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.774494556765163%\"\u003e\n \u003cp\u003e2.5%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.174183514774494%\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.618973561430794%\"\u003e\n \u003cp\u003e2.1%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38.25816485225506%\"\u003e\n \u003cp\u003eBacterial infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.174183514774494%\"\u003e\n \u003cp\u003e110\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.774494556765163%\"\u003e\n \u003cp\u003e11.4%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.174183514774494%\"\u003e\n \u003cp\u003e105\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.618973561430794%\"\u003e\n \u003cp\u003e12.1%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38.25816485225506%\"\u003e\n \u003cp\u003eOther types of infections\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.174183514774494%\"\u003e\n \u003cp\u003e98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.774494556765163%\"\u003e\n \u003cp\u003e10.2%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.174183514774494%\"\u003e\n \u003cp\u003e100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.618973561430794%\"\u003e\n \u003cp\u003e11.5%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38.25816485225506%\"\u003e\n \u003cp\u003eTMA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.174183514774494%\"\u003e\n \u003cp\u003e34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.774494556765163%\"\u003e\n \u003cp\u003e3.5%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.174183514774494%\"\u003e\n \u003cp\u003e33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.618973561430794%\"\u003e\n \u003cp\u003e3.8%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38.25816485225506%\"\u003e\n \u003cp\u003eBleeding\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.174183514774494%\"\u003e\n \u003cp\u003e48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.774494556765163%\"\u003e\n \u003cp\u003e5.0%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.174183514774494%\"\u003e\n \u003cp\u003e42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.618973561430794%\"\u003e\n \u003cp\u003e4.8%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38.25816485225506%\"\u003e\n \u003cp\u003eNoninfectious lung disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.174183514774494%\"\u003e\n \u003cp\u003e116\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.774494556765163%\"\u003e\n \u003cp\u003e12.0%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.174183514774494%\"\u003e\n \u003cp\u003e94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.618973561430794%\"\u003e\n \u003cp\u003e10.8%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38.25816485225506%\"\u003e\n \u003cp\u003eLiver disease (including SOS)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.174183514774494%\"\u003e\n \u003cp\u003e36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.774494556765163%\"\u003e\n \u003cp\u003e3.7%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.174183514774494%\"\u003e\n \u003cp\u003e36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.618973561430794%\"\u003e\n \u003cp\u003e4.1%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38.25816485225506%\"\u003e\n \u003cp\u003eOther types of organ damage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.174183514774494%\"\u003e\n \u003cp\u003e74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.774494556765163%\"\u003e\n \u003cp\u003e7.7%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.174183514774494%\"\u003e\n \u003cp\u003e72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.618973561430794%\"\u003e\n \u003cp\u003e8.3%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38.25816485225506%\"\u003e\n \u003cp\u003eOther cause\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.174183514774494%\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.774494556765163%\"\u003e\n \u003cp\u003e1.9%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.174183514774494%\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.618973561430794%\"\u003e\n \u003cp\u003e2.1%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eGVHD, graft versus host disease; SOS, sinusoidal obstruction syndrome; TMA, thrombotic microangiopathy; y/o, years old\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4a. Multivariate analysis for OS in the older group\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"642\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"41.12149532710281%\" colspan=\"2\" rowspan=\"2\"\u003e\n \u003cp\u003eFactor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.797507788161994%\" rowspan=\"2\"\u003e\n \u003cp\u003eHR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.439252336448597%\" colspan=\"2\"\u003e\n \u003cp\u003e95% CI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.641744548286605%\" rowspan=\"2\"\u003e\n \u003cp\u003eP-value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"49.735449735449734%\"\u003e\n \u003cp\u003eLower\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50.264550264550266%\"\u003e\n \u003cp\u003eUpper\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.5202492211838%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eDx to HSCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.601246105919003%\"\u003e\n \u003cp\u003e\u0026lt;1 year\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.797507788161994%\"\u003e\n \u003cp\u003eRef.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.641744548286605%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.797507788161994%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.641744548286605%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.014256619144604%\"\u003e\n \u003cp\u003e\u0026gt;1 year\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.34826883910387%\"\u003e\n \u003cp\u003e0.81\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.144602851323828%\"\u003e\n \u003cp\u003e0.66\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.34826883910387%\"\u003e\n \u003cp\u003e0.98\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.144602851323828%\"\u003e\n \u003cp\u003e0.03*\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.5202492211838%\" rowspan=\"3\" valign=\"top\"\u003e\n \u003cp\u003eDisease stage at HSCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.601246105919003%\"\u003e\n \u003cp\u003eEarly\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.797507788161994%\"\u003e\n \u003cp\u003eRef.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.641744548286605%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.797507788161994%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.641744548286605%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.014256619144604%\"\u003e\n \u003cp\u003eIntermediate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.34826883910387%\"\u003e\n \u003cp\u003e1.06\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.144602851323828%\"\u003e\n \u003cp\u003e0.82\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.34826883910387%\"\u003e\n \u003cp\u003e1.37\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.144602851323828%\"\u003e\n \u003cp\u003e0.66\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.014256619144604%\"\u003e\n \u003cp\u003eLate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.34826883910387%\"\u003e\n \u003cp\u003e2.08\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.144602851323828%\"\u003e\n \u003cp\u003e1.71\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.34826883910387%\"\u003e\n \u003cp\u003e2.53\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.144602851323828%\"\u003e\n \u003cp\u003e\u0026lt;0.01*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.5202492211838%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eCell source\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.601246105919003%\"\u003e\n \u003cp\u003eBM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.797507788161994%\"\u003e\n \u003cp\u003eRef.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.641744548286605%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.797507788161994%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.641744548286605%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.014256619144604%\"\u003e\n \u003cp\u003ePB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.34826883910387%\"\u003e\n \u003cp\u003e0.97\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.144602851323828%\"\u003e\n \u003cp\u003e0.80\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.34826883910387%\"\u003e\n \u003cp\u003e1.17\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.144602851323828%\"\u003e\n \u003cp\u003e0.71\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.5202492211838%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eF to M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.601246105919003%\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.797507788161994%\"\u003e\n \u003cp\u003eRef.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.641744548286605%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.797507788161994%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.641744548286605%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.014256619144604%\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.34826883910387%\"\u003e\n \u003cp\u003e1.19\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.144602851323828%\"\u003e\n \u003cp\u003e0.98\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.34826883910387%\"\u003e\n \u003cp\u003e1.45\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.144602851323828%\"\u003e\n \u003cp\u003e0.08\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.5202492211838%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003ePerformance status\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.601246105919003%\"\u003e\n \u003cp\u003e0\u0026ndash;1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.797507788161994%\"\u003e\n \u003cp\u003eRef.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.641744548286605%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.797507788161994%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.641744548286605%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.014256619144604%\"\u003e\n \u003cp\u003e2\u0026ndash;4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.34826883910387%\"\u003e\n \u003cp\u003e2.34\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.144602851323828%\"\u003e\n \u003cp\u003e1.86\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.34826883910387%\"\u003e\n \u003cp\u003e2.96\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.144602851323828%\"\u003e\n \u003cp\u003e\u0026lt;0.01*\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.5202492211838%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eUse of add. chem\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.601246105919003%\"\u003e\n \u003cp\u003eNone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.797507788161994%\"\u003e\n \u003cp\u003eRef.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.641744548286605%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.797507788161994%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.641744548286605%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.014256619144604%\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.34826883910387%\"\u003e\n \u003cp\u003e1.35\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.144602851323828%\"\u003e\n \u003cp\u003e1.06\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.34826883910387%\"\u003e\n \u003cp\u003e1.70\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.144602851323828%\"\u003e\n \u003cp\u003e0.01*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAdd. chem. drug, additional chemotherapeutic drug; BM, bone marrow; CI, confidence interval; Disease stage, categorized according to EBMT risk score [20]; Dx, diagnosis; F to M, HSCT from female donor to male recipient; HR, hazard ratio; HSCT, hematopoietic stem cell transplantation; OS, overall survival; PB, peripheral blood; Ref., reference; *, significant difference (p\u0026lt;0.05)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4b. Multivariate analysis for NRM in the older group\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"642\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"41.12149532710281%\" colspan=\"2\" rowspan=\"2\"\u003e\n \u003cp\u003eFactor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.797507788161994%\" rowspan=\"2\"\u003e\n \u003cp\u003eHR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.439252336448597%\" colspan=\"2\"\u003e\n \u003cp\u003e95% CI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.641744548286605%\" rowspan=\"2\"\u003e\n \u003cp\u003eP-value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"49.735449735449734%\"\u003e\n \u003cp\u003eLower\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50.264550264550266%\"\u003e\n \u003cp\u003eUpper\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.5202492211838%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eDisease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.601246105919003%\"\u003e\n \u003cp\u003eMyeloid\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.797507788161994%\"\u003e\n \u003cp\u003eRef.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.641744548286605%\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.797507788161994%\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.641744548286605%\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.014256619144604%\"\u003e\n \u003cp\u003eOthers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.34826883910387%\"\u003e\n \u003cp\u003e1.44\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.144602851323828%\"\u003e\n \u003cp\u003e1.01\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.34826883910387%\"\u003e\n \u003cp\u003e2.05\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.144602851323828%\"\u003e\n \u003cp\u003e0.04*\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.5202492211838%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eDx to HSCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.601246105919003%\"\u003e\n \u003cp\u003e\u0026lt;1 y\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.797507788161994%\"\u003e\n \u003cp\u003eRef.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.641744548286605%\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.797507788161994%\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.641744548286605%\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.014256619144604%\"\u003e\n \u003cp\u003e\u0026gt;1y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.34826883910387%\"\u003e\n \u003cp\u003e1.40\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.144602851323828%\"\u003e\n \u003cp\u003e1.11\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.34826883910387%\"\u003e\n \u003cp\u003e1.78\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.144602851323828%\"\u003e\n \u003cp\u003e0.01*\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.5202492211838%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003ePerformance status\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.601246105919003%\"\u003e\n \u003cp\u003e0\u0026ndash;1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.797507788161994%\"\u003e\n \u003cp\u003eRef.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.641744548286605%\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.797507788161994%\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.641744548286605%\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.014256619144604%\"\u003e\n \u003cp\u003e2\u0026ndash;4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.34826883910387%\"\u003e\n \u003cp\u003e1.32\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.144602851323828%\"\u003e\n \u003cp\u003e0.92\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.34826883910387%\"\u003e\n \u003cp\u003e1.89\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.144602851323828%\"\u003e\n \u003cp\u003e0.13*\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.5202492211838%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eUse of TBI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.601246105919003%\"\u003e\n \u003cp\u003eNone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.797507788161994%\"\u003e\n \u003cp\u003eRef.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.641744548286605%\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.797507788161994%\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.641744548286605%\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.014256619144604%\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.34826883910387%\"\u003e\n \u003cp\u003e1.45\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.144602851323828%\"\u003e\n \u003cp\u003e1.15\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.34826883910387%\"\u003e\n \u003cp\u003e1.82\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.144602851323828%\"\u003e\n \u003cp\u003e\u0026lt;0.01*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.5202492211838%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eUse of add. chem. drug\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.601246105919003%\"\u003e\n \u003cp\u003eNone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.797507788161994%\"\u003e\n \u003cp\u003eRef.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.641744548286605%\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.797507788161994%\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.641744548286605%\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.014256619144604%\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.34826883910387%\"\u003e\n \u003cp\u003e1.74\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.144602851323828%\"\u003e\n \u003cp\u003e1.25\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.34826883910387%\"\u003e\n \u003cp\u003e2.42\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.144602851323828%\"\u003e\n \u003cp\u003e\u0026lt;0.01*\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAdd. chem. drug, additional chemotherapeutic drug; CI, confidence interval; Dx, diagnosis; HR, hazard ratio; HSCT, hematopoietic stem cell transplantation; NRM, non-relapse mortality; Ref., reference; TBI, total body irradiation; *, significant difference (p\u0026lt;0.05)\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Allogeneic hematopoietic stem cell transplantation, conditioning regimen, busulfan, older people","lastPublishedDoi":"10.21203/rs.3.rs-4227690/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4227690/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Fludarabine and myeloablative doses of busulfan-based regimens (FluBu4) are used in a wide age range as a reduced toxicity conditioning regimen for allogeneic hematopoietic stem cell transplantation (HSCT). However, their tolerability in older people has not been adequately examined. This retrospective study analyzed data from Transplant Registry Unified Management Program in Japan. Patients who were \u003e15 years old (y/o), had hematological malignancies, and received their first HSCT using FluBu4 between 2006 and 2017 were included. They were categorized into the younger group (\u003c60 y/o, N = 1295) and the older group (≥60 y/o, N = 993). The 3-year overall survival (OS) rate after HSCT was significantly worse in the older group than in the younger group (P \u003c 0.01, 39.9% versus 48.5%). The 3-year non-relapse mortality (NRM) was significantly higher in the older group than in the younger group (P \u003c 0.01, 30.9% versus 23.0%), and the 3-year cumulative incidence of relapse was comparable between the groups. According to the multivariate analysis, age ≥ 60 years was significantly associated with poor OS (P \u003c 0.01) and high NRM (P \u003c 0.01). In subgroup analysis of the older group, the use of additional chemotherapeutic drugs to FluBu4 was significantly associated with poor OS (P = 0.01) and high NRM (P \u003c 0.01). Total body irradiation was significantly associated with high NRM (P \u003c 0.01) and 1-year incidence of sinusoidal obstruction syndrome (P \u003c 0.01) but not with OS. Thus, FluBu4 should be used with caution in older people.","manuscriptTitle":"Increased non-relapse mortality in older people with allogeneic hematopoietic stem cell transplantation using fludarabine and myeloablative dose of busulfan-based regimen","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-05-02 20:07:11","doi":"10.21203/rs.3.rs-4227690/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"2446a6a9-3cca-4b1a-b216-7760426e8b79","owner":[],"postedDate":"May 2nd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-09-18T19:01:14+00:00","versionOfRecord":[],"versionCreatedAt":"2024-05-02 20:07:11","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4227690","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4227690","identity":"rs-4227690","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}