A Randomized Pilot Trial comparing Anti-Thymocyte Globulin (ATG) with ATG plus Post Transplant Cyclophosphamide (PTCy) for Prophylaxis against Acute and Chronic Graft Versus Host Disease (GVHD) in Matched Donor Hematopoietic Cell Transplants (HCT)

A Randomized Pilot Trial comparing Anti-Thymocyte Globulin (ATG) with ATG plus Post Transplant Cyclophosphamide (PTCy) for Prophylaxis against Acute and Chronic Graft Versus Host Disease (GVHD) in Matched Donor Hematopoietic Cell Transplants (HCT) | 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 Article A Randomized Pilot Trial comparing Anti-Thymocyte Globulin (ATG) with ATG plus Post Transplant Cyclophosphamide (PTCy) for Prophylaxis against Acute and Chronic Graft Versus Host Disease (GVHD) in Matched Donor Hematopoietic Cell Transplants (HCT) Irwin Walker, Uday Deotare, Mohamed Elemary, Mahmoud Elsawy, Geneviève Gallagher, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8949910/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 11 You are reading this latest preprint version Abstract In a randomized pilot trial we compared ATG (standard Arm A, 4.5 mg/kg) with ATG plus PTCy (experimental Arm BE, ATG 4.5 mg/kg, PTCy 100 mg/kg). The primary safety endpoint was overall survival at 100 days. We analyzed 79 patients with AML (n=55) or MDS (n=24). Median age (range) was 59 (19 to 74), 47 (59.5 %) were male. Conditioning was either myeloablative (n=49) or reduced intensity (n=30). Donors were 8/8 HLA-matched. Overall survival at 100 days was 95.0% (37 of 39 patients) vs 94.9% (38 of 40 patients) in arm A vs arm BE (p>0.9). In arms A versus BE, serious adverse events (SAEs) occurred in 26 (65.0%) and 25 (64.1%) patients, graft failure occurred in 3 and 1 patients (p>0.9), median (range) days to neutrophil engraftment were 19 (10-45) versus 22 (15-56) days p=0.007), cytomegalovirus and Epstein-Barr virus reactivations occurred in 11 and 7 patients (p=0.45) and in 6 and 5 patients (p=0.29). Overall survival at 12-months was 72.5% versus 75.8% (p-0.79), cumulative incidence at 6 months of relapse was 15.0% versus 15.7% (p=0.88) and of non-relapse mortality (NRM) 7.5% versus 8.0 (p=0.45). The combination of ATG and PTCy can safely be used in phase III trials. Health sciences/Medical research/Clinical trial design/Randomized controlled trials Health sciences/Medical research/Stem-cell research Figures Figure 1 Figure 2 INTRODUCTION Prevention of graft-versus-host disease (GVHD), the most important complication of allogeneic hematopoietic cell transplantation (HCT), is most often undertaken with calcineurin inhibitors (CNI), together with other agents either anti-thymocyte globulin (ATG) or Post-Transplant Cyclophosphamide (PTCy). Each of these agents has efficacy demonstrated in multiple randomized trials, but they have not been compared directly in a randomized trial. Two randomized trials are in progress, one comparing PTCy to ATG (ISRCTN50290131) and one comparing PTCy to anti-T-lymphoblastoid cell line globulin (ATLG), which is similar to ATG (NCT05153226). ATG, In randomized trials, has consistently decreased the incidence of GVHD compared with the incidence in patients not receiving ATG 1–5 . These trials with ATG have been in matched transplants using myeloablative conditioning, just one trial 3 having included cases receiving non-myeloablative conditioning, these cases also showing benefit. PTCy has become standard for use in haploidentical donor transplants and is commonly used in patients with lesser degrees of mismatch; however, its use in matched donor transplants is more recent. PTCy added to standard prophylaxis has, like ATG, also shown superiority in randomized trials following both reduced and myeloablative conditioning 6,7 . By contrast, when PTCy was tested in the setting of myeloablative conditioning without CNI, there was no improvement compared with the group receiving standard prophylaxis with CNI 8 . This suggests that PTCy, and maybe ATG also, require the addition of a CNI for optimal benefit. Given that neither ATG nor PTCy in isolation completely prevents GVHD we became interested in combining both treatments together (ATG/PTCy) in an attempt to further improve results. A Medline search indicates that use of this combination has been widespread with over forty publications since 2020, including at least three registry-based studies, with varying conclusions reached. One randomized trial 9 was recently published, the study being halted at the time of interim analysis for futility to reach the hypothesized outcome. This research group proposed a phase III trial but there was sufficient concern about the safety of combining ATG and PTCy from the point of view of inducing viral reactivations or increasing the rate of disease relapse that a pilot trial was recommended. This pilot trial was designed as a phase III trial with two year follow up, with short term safety endpoints, and patients consented to be followed for two years and the results ultimately to be included within the phase III sample size. Funding for a phase III trial has been submitted. METHODS We performed a randomized, controlled, multi-centre, parallel group, open-label, pilot trial comparing standard ATG alone with ATG plus PTCy, to assess safety, randomizing 85 available patients. Patients consented to two years follow-up in anticipation of an expansion to phase III, as described in the CONSORT extension for pilot trials (Abbade LPF et al (2018) DOI 10.1186/s40409-018-0142-2 ). Eligibility and conduct Recipients were aged ≥ 16 years having either acute myeloid leukemia (AML) in remission, or myelodysplastic syndrome (MDS), and fulfilling centre criteria for transplant eligibility. Permitted preparative regimens could be myeloablative or reduced intensity. Reduced intensity regimens were fludarabine combined with either busulfan or melphalan; myeloablative regimes were busulfan combined with either fludarabine or cyclophosphamide. Donors were either related or unrelated and were fully HLA-matched (8/8) at HLA-A, HLA-B, HLA-C, or HLA-DRB1 loci using high resolution typing. Grafts were from peripheral blood. Supportive therapies were according to local institutional practices. We completed the study in six transplantation centres in Canada and two in Australia. Randomization and masking We used minimization 10 to assign patients to either arm A (ATG) or BE (ATG/PTCy). Minimization factors were a priori risk factors for cGVHD, relapse and mortality, these being participant age (16–30, 31–50, > 50); female donor for male recipient; choice of donor (related vs. unrelated); donor age ( 50); disease type; disease risk index; type of preparative regimen, and co-morbidity by augmented HCT-CI; transplant centre was included to balance for differences in support practices. The methodology to assign patients to each arm was as follows: The study statistician (T. Panzarella) prepared two randomization lists using a computer random number generator before the study began: 1) a simple randomization list where both treatments occur equally often; this list was only used when the two treatments had equal sums for the levels of the baseline prognostic factors; and 2) a list in which the treatment with the smaller total of patient levels occurs with probability 0.8 while the other treatment occurs with probability 0.2. Allocation occurred centrally by Ozmosis Research Inc. Toronto, Canada, and the process was therefore concealed from staff at the participant’s centre. Though the assignment process is not blinded it is objective and can be audited. Transplant Procedures Patients in the standard ATG group (A) received rabbit anti-thymocyte globulin (Thymoglobuline, Sanofi–Genzyme, Lyon, France) intravenously at a total dose of 4.5 mg/kg over 3 days (0.5 mg/kg on day − 2, and 2.0 mg/kg on days − 1 and + 1). The dose was calculated on actual body weight, and no reductions were specified. Dose interruptions for reactions were permitted but it was expected that the entire daily dose would be infused on the same day as initiated. Patients in the experimental group (BE) received ATG as for group A and also received PTCy 50 mg/kg on post-transplant days 3 and 4. All patients received a CNI. Methotrexate 15 mg/m 2 on day + 1 and 10 mg/m 2 on days + 3, +6, and + 11 was added for patients receiving myeloablative conditioning and randomized to group A, but not to those randomized to group BE, who received a CNI alone. Mycophenolate (3 centres) or methotrexate (3 centres) was added to those receiving reduced intensity conditioning and randomized to group A but not to those randomized to group BE who received a CNI alone. Study data were collected and entered by site personnel into electronic case report forms (eCRFs) and managed by Ozmosis Inc, Toronto in accordance with national and international regulations and standards. Monitoring was carried out by the Data and Safety Monitoring Committee of Cell Therapy and Transplantation Canada. Adverse events were graded according to Common Terminology Criteria 5.0. Adverse events of specific interest, whether serious or not, also had to be reported, these being veno-occlusive disease, hemorrhagic cystitis, and those reactivations of Epstein-Barr virus (EBV) and cytomegalovirus (CMV) that required treatment according to individual centre protocols. Acute and chronic graft versus host disease were diagnosed and graded by standard criteria 11,12 . Supportive care followed institutional practices except that the use of ganciclovir or foscarnet for primary prophylaxis and the routine use of growth factors, gamma globulin, or alemtuzumab, were not allowed. Letermovir was allowed. Treatment of acute GVHD and chronic GVHD was according to centre preferences. Patients filled out questionnaires related to quality of life and socio-demographics, results from which will be reported separately. Outcomes The study was designed to assess the safety of the experimental arm, prior to consideration of a subsequent efficacy (phase III) trial. The primary safety outcome was mortality, the expectation being that survival in experimental arm BE would be at least 90% that of the standard arm at 100 days post-transplant. Secondary safety endpoints were, incidence of serious infection, incidence of CMV reactivation, time to non-relapse mortality, time to all-cause mortality, incidence of graft rejection or failure, time to disease relapse, time to engraftment, incidence of EBV reactivation and post-transplant lymphoproliferative disorder; secondary efficacy endpoints were incidences of aGVHD and cGVHD, chronic graft versus host disease free- and relapse-free survival (CRFS), need for immunosuppressive therapy (IST) at 12 -months (Yes/No), and quality of life (to be reported separately). Time to neutrophil engraftment was the time from transplant (Day 0) to the first day of achieving an absolute neutrophil count of 0.5 x 109/L. Time to platelet engraftment was the time from transplant (Day 0) to the first day of achieving a platelet count of greater than 20x109/L without requiring platelet transfusions in the previous 7 days. Primary graft failure was the absence of neutrophil recovery (absolute neutrophil count less than 0.5 x 109/L) in patients surviving until at least Day + 28 post-transplant; secondary graft failure was a loss of neutrophil engraftment in the absence of primary disease. Statistical analysis The primary analysis was planned according to the intention-to-treat principle; however, a modified intention-to-treat population was used. A small number of participants who were randomized but subsequently found to be ineligible were excluded and did not undergo follow-up. All remaining participants were analyzed according to their randomized treatment assignment. Because immune marker levels and time to neutrophil engraftment exhibited skewed distributions, comparisons between treatment groups were performed using the Wilcoxon rank-sum test. Proportions between the two treatment groups were compared using Fisher’s exact test. Time-to-event endpoints were calculated from the date of transplantation using the Kaplan–Meier method or, when competing risks were present, the cumulative incidence (CI) method. Between-group differences were assessed using the log-rank test or Gray’s test, respectively. Overall survival was defined as the time from transplantation to death from any cause or, for surviving participants, to the date of last follow-up. Relapse-free survival was defined as the time to relapse or death, whichever occurred first. Chronic graft-versus-host disease (GVHD)– and relapse-free survival was defined as the time to the earliest of the following events: (1) moderate or severe chronic GVHD, (2) relapse, or (3) death. For analyses of non-relapse-related mortality (NRM), relapse-related death was treated as a competing risk; for time to relapse, death from other cause was treated as a competing event. For acute GVHD, death was considered a competing risk. In analyses of Grade II–IV acute GVHD, Grade I events were censored at the last follow-up; similarly, in analyses of Grade III–IV acute GVHD, Grades I and II events were censored. All analyses were conducted using SAS version 9.4 (SAS Institute Inc., Cary, NC) in SAS Studio. Funding source and sponsorship This trial was sponsored by McMaster University, Hamilton, Ontario, Canada, registered at clinicaltrials.gov (NCT04202835) on November 29, 2019, and funded by Sanofi. This was an investigator-initiated study and Sanofi had no role in study design, data collection, data analysis, data interpretation, or writing of the report. Trial management was by Ozmosis Research Inc. Toronto, Canada. Authors had no conflicts of interest other than for the above funding from Sanofi, the manufacturer of ATG (Thymoglobulin), which was administered equally in both arms of the trial. RESULTS The study database was locked after all patients had been followed for at least 12 months, at which time median follow up of living patients was 24.1 months (range 11.89- 26.71) and 23.7 months (range 11.99-25.07) for arms A and BE respectively. Our intention was to transplant 80 eligible patients. Between October 26th, 2020, and February 7th, 2024, we randomly assigned 85 patients (Figure 1), six of whom were excluded leaving 79 patients available for analysis. Of the six patients, five were found to be ineligible and one had his/her transplantation cancelled. Forty patients were analyzed from arm A (ATG alone) and 39 patients from experimental arm BE (ATG/PTCy). Baseline characteristics did not differ between the treatment groups (Table 1). Median age was 59 years, range 19-74 with males 59.5%. Outcomes at 100 days following transplantation, the primary endpoint. Results, all at day 100, are summarized in Table 2. Thirty-eight (38) of 40 patients (95.0%) in arm A and thirty-seven (37) of 39 patients (94.9%) in arm BE survived to 100 days (primary endpoint; p>0.9). In arm A, deaths were due to cardiac arrest (n=1) and subdural hematoma (n=1); in arm BE, deaths were due to acute respiratory distress syndrome (n=1) and post-transplant lymphoproliferative disorder (n=1). Acute graft-versus-host disease occurred in 15 patients in arm A and 6 in arm BE (p=0.041). Grades II–IV AGVHD were reported in 6 and 3 patients (p=0.49), and grades III–IV in 3 and 0 patients (p=0.24), in arms A and BE. At day 100, two patients in each arm were receiving systemic corticosteroids. Serious adverse events were reported in 26 patients (65.0%) in arm A and 25 patients (64.1%) in arm BE (p>0.9). Graft failure at 28 days (standard criteria), occurred in 3 patients in arms A and 1 patient in arm BE (p=0.62), with all 4 patients achieving engraftment by 56 days. Median time to neutrophil engraftment was 19 days (range, 10–45) in arm A and 22 days (range, 15–56) in arm BE (p=0.007). Cytomegalovirus reactivation requiring treatment occurred in 11 patients in arm A and 6 in arm BE (p=0.45), while Epstein–Barr virus reactivation occurred in 7 and 5 patients (p>0.9), respectively. Median CD4 counts were 63 cells/mm (IQR = interquartile range 40.0-125.0) in arm A and 59.5 (IQR 28.5-137.5) in arm BE (p=0.58). Median serum IgG levels were 740 mg/dL(IQR 629-850) in arm A and 620 (IQR 550-794) in arm BE (p=0.16). Median CD8 levels were 190 cells/mm 3 (IQR 55-390) in arm A and 240 (IQR 70-473) in arm BE (p=0.42). Complete immune marker results at 100 days, together with results at one year, are summarized in Table 3 and there were no statistically significant differences between the arms. Outcomes at long-term follow-up After a median follow up of 23.9 months (range 11.89-26.71), 53 patients remained alive and their data was analyzed. The major endpoints are summarized and illustrated in Table 4 and Figure 2 (A-D). Overall survival (Figure 2A) at 12-months was 72.5% (% SE 7.1) in arm A and 75.8% (SE 7.0) in arm BE (p=0.79). Cumulative incidence of NRM at 6-months (Figure 2B) was 7.5% (SE 4.2) in arm A and 8.0% (SE 4.) in arm BE (Gray’s test p=0.45). Relapses were seen in 8 patients in each arm. Cumulative incidence of relapse at 6-months (Figure 2C) was 15.0% (SE 5.7) in arm A and 15.7% (SE 6.0) in arm BE (Gray’s test p=0.88). Relapse-free survival at 12-months was 60.0% (SE 7.8) in arm A and 65.9% (SE 7.7) in arm BE (log rank p=0.66). Moderate or severe chronic GVHD- and relapse-free survival (CRFS; Figure 2D) at 12-months was 56.1% (SE 7.8) in arm A and 60.6% (SE 7.9) in arm BE (log rank p=0.69). Acute GVHD (all grades) was seen in 18 patients in arm A and 18 patients in arm BE, and CI at 6-months was 42.5% (SE 8.0) in arm A and 23.7% (SE 7.0) in arm BE (Gray’s test p=0.04). Acute GVHD Grades II-IV were seen in 11 in arm A and 5 patients in arm BE, and CI at 6-months was 25.0% (SE7.0) in arm A and 13.1% (SE 5.6) in arm BE, (Gray’s test p=0.13), and grade III/IV in 5 patients in arm A and 1 patient in arm BE, CI at 6-months 10.0 (SE 4.8) and 2.7% (SE 2.7), Gray’s test p=0.10) in arms A and BE respectively. Late AGVHD (after day 100) occurred in 3 patients in each arm. CGVHD has been reported to date in 6 patients and 3 patients in arms A and BE respectively with moderate or severe grades in 2 patients in each arm. Steroid and/or immunosuppressive agents were being administered at 12 months by 6 patients and 2 patients in arms A and BE respectively. DISCUSSION This randomized pilot trial, intended to assess the safety of ATG/PTCy when compared with standard ATG, achieved its primary endpoint of survival in the ATG/PTCy arm being at least 90% of that in the ATG arm, at 100 days. A variety of secondary safety endpoints showed no excess toxicity in the experimental arm (ATG/PTCy), nor, after minimal follow up of 24 months, adverse effects on survival, rate of infections or rate of disease relapse. Time to completed accrual to this trial was much longer than intended, due to staffing and administrative complications of the COVID era; a benefit was a longer than intended follow-up period, allowing assessment of longer-term outcomes supporting the 100-day observations, pointing to safety of the combined approach. A weakness of this study is defining safety under a limited primary endpoint of short-term survival. Survival may be an insensitive measure of safety given that there are a wide variety of potential toxicities that would also be unacceptable for further use of the experimental treatment (ATG/PTCy). We considered, however, that a primary endpoint based on a variety of toxicities would be difficult to define, and debatable, while a decrease of survival would provide an undebatable end to further investigation of the experimental treatment. Nevertheless, the concept of safety in this trial is well supported by a variety of secondary endpoints describing the well-known complications of bone marrow transplantation. The choice of 100 days relates to the span of time during which most transplant-related toxicities occur but the results at long term follow up also point to safety. We consider, based on results in this trial, in particular those pointing to safety and the trend in the incidence of acute GVHD, together with the already widespread use of the combination 13,14 , that PTCy/ATG is sufficiently safe to be further investigated for the prevention of GVHD in a large randomized trial sufficiently powered to assess incidences of acute and chronic GVHD. Declarations Corresponding author: Irwin Walker [email protected] Author contributions: IW, TP and KP designed the study; TP performed the analysis; correlative studies were conducted by KRS (biological markers of GVHD) and JS (ATG pharmacokinetics); Elsawy guided quality of life studies; all authors reviewed the draft and contributed to the final manuscript. Registration: clinicaltrials.gov (NCT04202835), November 29, 2019 Funding: This study was funded by Sanofi as an investigator-initiated trial, being conducted at arm’s length, with Sanofi not contributing to the design, conduct, analysis or final manuscript. The Desroches Bone Marrow Transplant Fund, McMaster University, Hamilton, Canada, provided funding for protocol development. Data sharing: No clinical trial data has been shared outside of the authors and coordinating centre. The trial protocol will be made available on request. Disclosures: All authors received research funds from Sanofi, either directly or indirectly. There are no other relevant disclosures. Ethics statement: The study was conducted in accordance with the Declaration of Helsinki and was approved by Clinical Trials Ontario (CTO Stream #1852) and by ethics committees at participating centres. Written informed consent was obtained from all participants prior to their enrollment in the study. References Bacigalupo A. Lamparelli T. Barisione G. Bruzzi P. Guidi S. Alessandrino PE. di Bartolomeo P. Oneto R. Bruno B. Sacchi N. van Lint MT. Bosi A. Gruppo Italiano Trapianti Midollo Osseo (GITMO). Thymoglobulin prevents chronic graft-versus-host disease, chronic lung dysfunction, and late transplant-related mortality: long-term follow-up of a randomized trial in patients undergoing unrelated donor transplantation. Biol Blood Marrow Transplant . 2006;12(5):560-565. Finke J, Schmoor C, Bethge WA, et al. Long-term outcomes after standard graft-versus-host disease prophylaxis with or without anti-human-T-lymphocyte immunoglobulin in haemopoietic cell transplantation from matched unrelated donors: final results of a randomised controlled trial. The LancetHaematology . 2017;4(6):e293-e301. Walker I, Panzarella T, Couban S, et al. Addition of anti-thymocyte globulin to standard graft-versus-host disease prophylaxis versus standard treatment alone in patients with haematological malignancies undergoing transplantation from unrelated donors: final analysis of a randomised, open-label, multicentre, phase 3 trial. Lancet Haematol . Published online January 2020:S2352302619302200. doi:10.1016/S2352-3026(19)30220-0 Soiffer RJ, Kim HT, McGuirk J, et al. Prospective, Randomized, Double-Blind, Phase III Clinical Trial of Anti–T-Lymphocyte Globulin to Assess Impact on Chronic Graft-Versus-Host Disease–Free Survival in Patients Undergoing HLA-Matched Unrelated Myeloablative Hematopoietic Cell Transplantation. J Clin Oncol . 2017;35(36):4003-4011. doi:10.1200/JCO.2017.75.8177 Chang YJ, Wu DP, Lai YR, et al. Antithymocyte Globulin for Matched Sibling Donor Transplantation in Patients With Hematologic Malignancies: A Multicenter, Open-Label, Randomized Controlled Study. J Clin Oncol . Published online July 10, 2020:JCO.20.00150. doi:10.1200/JCO.20.00150 Bolaños-Meade J, Hamadani M, Wu J, et al. Post-Transplantation Cyclophosphamide-Based Graft-versus-Host Disease Prophylaxis. N Engl J Med . 2023;388(25):2338-2348. doi:10.1056/NEJMoa2215943 Curtis DJ, Patil SS, Reynolds J, et al. Graft-versus-Host Disease Prophylaxis with Cyclophosphamide and Cyclosporin. N Engl J Med . Published online June 13, 2025:NEJMoa2503189. doi:10.1056/NEJMoa2503189 Luznik L, Pasquini MC, Logan B, et al. Randomized Phase III BMT CTN Trial of Calcineurin Inhibitor–Free Chronic Graft-Versus-Host Disease Interventions in Myeloablative Hematopoietic Cell Transplantation for Hematologic Malignancies. J Clin Oncol . 2022;40(4):356-368. doi:10.1200/JCO.21.02293 Xu ZL, Han TT, Zhu XL, et al. Randomized trial of anti-thymocyte globulin plus lowdose post-transplant cyclophosphamide to prevent graft-versus- host disease in haploidentical transplantation. Haematologica . 2025;110(12):2965-2973. doi:10.3324/haematol.2025.287504 Scott NW, McPherson GC, Ramsay CR, Campbell MK. The method of minimization for allocation to clinical trials. a review. Control Clin Trials . 2002;23(6):662-674. Harris AC, Young R, Devine S, et al. International, Multicenter Standardization of Acute Graft-versus-Host Disease Clinical Data Collection: A Report from the Mount Sinai Acute GVHD International Consortium. Biol Blood Marrow Transplant J Am Soc Blood Marrow Transplant . 2016;22(1):4-10. doi:10.1016/j.bbmt.2015.09.001 Jagasia MH, Greinix HT, Arora M, et al. National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2014 Diagnosis and Staging Working Group Report. Biol Blood Marrow Transplant J Am Soc Blood Marrow Transplant . 2014;(Journal Article). doi:10.1016/j.bbmt.2014.12.001; DeZern A, Zahurak ML, Symons HJ, et al. 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Factor Standard Arm A ATG N (%) Experimental Arm BE ATG + PTCy N (%) 40 39 Patient Age 16 – 30 3 (7.5) 2 (5.1) 31 – 50 10 (25) 12 (30.8) > 50 27 (67.5) 25 (64.1) Female donor for male recipient Yes 7 (17.5) 6 (15.4) No 33 (82.5) 33 (84.6) Disease type MDS 12 (30) 12 (30.8) AML 28 (70) 27 (69.2) Choice of donor Related 14 (35) 14 (35.9) Unrelated 26 (65) 25 (64.1) Donor Age ≤ 30 19 (47.5) 17 (43.6) 31 – 50 11 (27.5) 12 (30.8) > 50 10 (25) 10 (25.6) Type of preparative regimen Myeloablative 27 (67.5) 22 (56.4) Reduced Intensity 13 (32.5) 17 (43.6) Disease risk index Very high 0 (0) 1 (2.6) High 12 (30) 12 (30.8) Intermediate 23 (57.5) 24 (61.5) Low 5 (12.5) 2 (5.1) Co-morbidity by augmented HCT-Cl 0 – 3 27 (67.5) 25 (64.1) > 3 13 (32.5) 14 (35.9) Site Cancer Care Manitoba 3 (7.5) 3 (7.7) Hamilton Health Sciences – Juravinski Cancer Centre 18 (45) 17 (43.6) University Hospital – London Health Sciences Centre 7 (17.5) 6 (15.4) Saskatoon Cancer Centre 2 (5) 1 (2.6) CHU de Quebec-Hopital l’Enfant-Jesus 2 (5) 3 (7.7) Saint Vincent’s Hospital 1 (2.5) 1 (2.6) Royal North Shore Hospital 2 (5) 2 (5.1) QEII Health Sciences Centre 5 (12.5) 6 (15.4) Table 2. Summary of outcomes at 100 days post transplantation. Results of all immune markers at 100 days and one year are seen in table 3. Arm Arm A ATG N (%) Arm BE ATG+PTCy N (%) p-value Subjects 40 39 Survival to 100 days 38 (95.0) 37 (94.9) >0.9 Subjects with SAEs 26 (65.0) 25 (64.1) >0.9 AGVHD grades I-IV 15 (37.5) 6 (15.4) 0.041 Grade II-IV 6 (15.0) 3 (7.7) 0.49 Grade III-IV 3 (7.5) 0 (0.0) 0.24 Neutrophil engraftment days (range) 19 (10-45) 22 (15-56) 0.007 Graft failure at 28 days 3 (7.5) 1(2.6) 0.62 CMV reactivation 11 (27.5) 7 (17.9) 0.45 EBV reactivation 6 (15.0) 5 (12.8) 0.29 Steroid use at 100 days 2 (5.0) 2 (5.1%) >0.9 Table 3. Immune marker (CD4, CD8, IgG) levels at Day 100 and One Year. IQR=interquartile range. Arm CD4 (Day 100) CD8 (Day 100) IgG (Day 100) CD4 (1 Year) CD8 (1 Year) IgG (1 Year) Standard Arm ATG Median 63 (n=34) 190 (n=33) 740 (n=35) 140 (n=28) 317 (n=28) 773 (n=28) IQR 40-125 55-390 629-850 106-270 170-731 534-1045 Experimental Arm ATG + PTCy Median 59.5 (n=28) 240 (n=28) 620 (n=29) 190 (n=22) 378.5 (n=22) 920 (n=21) IQR 29-138 70-473 550-794 140-271 197-890 700-992 P -value (Wilcoxon rank-sum test) 0.58 0.42 0.16 0.48 0.76 0.51 Normal ranges : CD4: 500-1200 cells/mm 3 CD8: 150-1000 cells/mm 3 IgG: 600-1640 mg/dL Table 4. Overall results at long term follow up. Arm Arm A ATG Arm BE ATG+PTCy p-value Subjects living 27 26 Median FU (range) 24.1 (11.89, 26.71) 23.7 (11.99, 25.07) Time to Relapse (CI%, 6 mths, SE) 15.0 (5.7) 15.7 (6.0) 0.88 Relapse-Free Survival (%,12 mths, SE) 60.0 (7.8) 65.9 (7.7) 0.66 Time to NRM (CI%, 6mths, SE) 7.5 (4.2) 8.0 (4.5) 0.45 Overall Survival (%, 12 mths, SE) 72.5 (7.1) 75.8 (7.0) 0.79 CRFS (12 mths, %) 56.1% 60.6% 0.69 Additional Declarations The authors have declared there is NO conflict of interest to disclose. 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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-8949910","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":603590698,"identity":"503e4742-896b-4992-8b00-4524479da163","order_by":0,"name":"Irwin Walker","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA20lEQVRIiWNgGAWjYFAC5mYgISFHihZGsBZjCCeBeC0MiQ1EazE4frDZ4OMei/S17acTP/78YZPPwH74AX4tZxKbE2c8k8jddiZ3szRPQpplA0+aAV4tZgcSmw/zHABqucG7QZoh4bABgwQDAS3nHzYf/nNAIt3sBu/mnz8S/gO1sH/Ar+VGYnMywwGJBKCWbRI8CQeAWnjw22J/42GzYc8BCUOgX7ZZ86QlG7Dx5BTg1SLZn3xY4seBOnmz42c33/xhY2fAz358A14tmICNRPWjYBSMglEwCrAAAGLqR+DF2kFLAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0003-0430-3837","institution":"McMaster University and Juravinski Cancer Centre","correspondingAuthor":true,"prefix":"","firstName":"Irwin","middleName":"","lastName":"Walker","suffix":""},{"id":603590699,"identity":"20732dc6-b6aa-44fe-b13a-1f26bf3a88c8","order_by":1,"name":"Uday Deotare","email":"","orcid":"https://orcid.org/0000-0001-9391-4204","institution":"Department of Medicine, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada","correspondingAuthor":false,"prefix":"","firstName":"Uday","middleName":"","lastName":"Deotare","suffix":""},{"id":603590700,"identity":"c4327df7-0965-4f39-a28f-403b8b551e64","order_by":2,"name":"Mohamed Elemary","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Mohamed","middleName":"","lastName":"Elemary","suffix":""},{"id":603590701,"identity":"da0ddc6d-2c36-47f7-8a06-60815125ed2a","order_by":3,"name":"Mahmoud Elsawy","email":"","orcid":"https://orcid.org/0000-0001-9872-2471","institution":"Division of Hematology, Dalhousie University, Halifax","correspondingAuthor":false,"prefix":"","firstName":"Mahmoud","middleName":"","lastName":"Elsawy","suffix":""},{"id":603590702,"identity":"5fb8e66c-5981-44b9-b6ce-2a3603916900","order_by":4,"name":"Geneviève Gallagher","email":"","orcid":"","institution":"CHU de Québec and Université Laval","correspondingAuthor":false,"prefix":"","firstName":"Geneviève","middleName":"","lastName":"Gallagher","suffix":""},{"id":603590703,"identity":"1caf82a8-ff7b-408d-b4b0-7a53d3ffc738","order_by":5,"name":"David Kliman","email":"","orcid":"https://orcid.org/0000-0002-2020-0275","institution":"Royal North Shore Hospital","correspondingAuthor":false,"prefix":"","firstName":"David","middleName":"","lastName":"Kliman","suffix":""},{"id":603590704,"identity":"8916db70-4130-42c1-b4b8-3dac1a1ca86a","order_by":6,"name":"Tony Panzarella","email":"","orcid":"https://orcid.org/0000-0002-3726-8313","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Tony","middleName":"","lastName":"Panzarella","suffix":""},{"id":603590705,"identity":"0e3ae38b-ef6f-4102-a982-c11fcd38b6e6","order_by":7,"name":"Nada Hamad","email":"","orcid":"https://orcid.org/0000-0001-7929-1450","institution":"St Vincent's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Nada","middleName":"","lastName":"Hamad","suffix":""},{"id":603590706,"identity":"ca2b5197-3443-4e57-869b-327e04ffef81","order_by":8,"name":"Kirk Schultz","email":"","orcid":"","institution":"University of British Columbia and B.C. Children's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Kirk","middleName":"","lastName":"Schultz","suffix":""},{"id":603590707,"identity":"22f80e42-8c3b-4e04-a05c-e5f26cf82ebe","order_by":9,"name":"Jan Storek","email":"","orcid":"https://orcid.org/0000-0002-7884-9122","institution":"University of Calgary","correspondingAuthor":false,"prefix":"","firstName":"Jan","middleName":"","lastName":"Storek","suffix":""},{"id":603590708,"identity":"e9d505c3-5713-40c3-a8ea-3792234be54d","order_by":10,"name":"Kristjan Paulson","email":"","orcid":"","institution":"CancerCare Manitoba","correspondingAuthor":false,"prefix":"","firstName":"Kristjan","middleName":"","lastName":"Paulson","suffix":""}],"badges":[],"createdAt":"2026-02-23 18:35:38","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8949910/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8949910/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":104595445,"identity":"517b72fa-ef02-41b7-b230-a1cdaed8460c","added_by":"auto","created_at":"2026-03-13 18:13:02","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":94331,"visible":true,"origin":"","legend":"\u003cp\u003eStudy profile\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8949910/v1/b569a1e623483c3b5209f09d.png"},{"id":104781363,"identity":"b6cd80ae-3fb1-4edc-b648-51635191d9dd","added_by":"auto","created_at":"2026-03-17 07:55:32","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":91099,"visible":true,"origin":"","legend":"\u003cp\u003eA) Overall survival B) Cumulative Incidence of NRM C) Cumulative incidence of disease relapse D) CRFS\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-8949910/v1/bb01ab989c16bf37cccb2fe8.png"},{"id":104784691,"identity":"d85a16af-bf9b-4230-8697-8d2f6ebdf3b6","added_by":"auto","created_at":"2026-03-17 08:08:39","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":840877,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8949910/v1/c9a984c8-08ef-4ec5-9c3f-4c3e3aff17a7.pdf"}],"financialInterests":"The authors have declared there is \u003cb\u003eNO\u003c/b\u003e conflict of interest to disclose.","formattedTitle":"A Randomized Pilot Trial comparing Anti-Thymocyte Globulin (ATG) with ATG plus Post Transplant Cyclophosphamide (PTCy) for Prophylaxis against Acute and Chronic Graft Versus Host Disease (GVHD) in Matched Donor Hematopoietic Cell Transplants (HCT)","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003ePrevention of graft-versus-host disease (GVHD), the most important complication of allogeneic hematopoietic cell transplantation (HCT), is most often undertaken with calcineurin inhibitors (CNI), together with other agents either anti-thymocyte globulin (ATG) or Post-Transplant Cyclophosphamide (PTCy). Each of these agents has efficacy demonstrated in multiple randomized trials, but they have not been compared directly in a randomized trial. Two randomized trials are in progress, one comparing PTCy to ATG (ISRCTN50290131) and one comparing PTCy to anti-T-lymphoblastoid cell line globulin (ATLG), which is similar to ATG (NCT05153226).\u003c/p\u003e \u003cp\u003eATG, In randomized trials, has consistently decreased the incidence of GVHD compared with the incidence in patients not receiving ATG\u003csup\u003e1\u0026ndash;5\u003c/sup\u003e. These trials with ATG have been in matched transplants using myeloablative conditioning, just one trial\u003csup\u003e3\u003c/sup\u003e having included cases receiving non-myeloablative conditioning, these cases also showing benefit. PTCy has become standard for use in haploidentical donor transplants and is commonly used in patients with lesser degrees of mismatch; however, its use in matched donor transplants is more recent. PTCy added to standard prophylaxis has, like ATG, also shown superiority in randomized trials following both reduced and myeloablative conditioning\u003csup\u003e6,7\u003c/sup\u003e. By contrast, when PTCy was tested in the setting of myeloablative conditioning without CNI, there was no improvement compared with the group receiving standard prophylaxis with CNI\u003csup\u003e8\u003c/sup\u003e. This suggests that PTCy, and maybe ATG also, require the addition of a CNI for optimal benefit.\u003c/p\u003e \u003cp\u003eGiven that neither ATG nor PTCy in isolation completely prevents GVHD we became interested in combining both treatments together (ATG/PTCy) in an attempt to further improve results. A Medline search indicates that use of this combination has been widespread with over forty publications since 2020, including at least three registry-based studies, with varying conclusions reached. One randomized trial\u003csup\u003e9\u003c/sup\u003e was recently published, the study being halted at the time of interim analysis for futility to reach the hypothesized outcome.\u003c/p\u003e \u003cp\u003eThis research group proposed a phase III trial but there was sufficient concern about the safety of combining ATG and PTCy from the point of view of inducing viral reactivations or increasing the rate of disease relapse that a pilot trial was recommended. This pilot trial was designed as a phase III trial with two year follow up, with short term safety endpoints, and patients consented to be followed for two years and the results ultimately to be included within the phase III sample size. Funding for a phase III trial has been submitted.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cp\u003eWe performed a randomized, controlled, multi-centre, parallel group, open-label, pilot trial comparing standard ATG alone with ATG plus PTCy, to assess safety, randomizing 85 available patients. Patients consented to two years follow-up in anticipation of an expansion to phase III, as described in the CONSORT extension for pilot trials (Abbade LPF et al (2018) DOI \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1186/s40409-018-0142-2\u003c/span\u003e\u003cspan address=\"10.1186/s40409-018-0142-2\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eEligibility and conduct\u003c/p\u003e \u003cp\u003eRecipients were aged\u0026thinsp;\u0026ge;\u0026thinsp;16 years having either acute myeloid leukemia (AML) in remission, or myelodysplastic syndrome (MDS), and fulfilling centre criteria for transplant eligibility. Permitted preparative regimens could be myeloablative or reduced intensity. Reduced intensity regimens were fludarabine combined with either busulfan or melphalan; myeloablative regimes were busulfan combined with either fludarabine or cyclophosphamide. Donors were either related or unrelated and were fully HLA-matched (8/8) at HLA-A, HLA-B, HLA-C, or HLA-DRB1 loci using high resolution typing. Grafts were from peripheral blood. Supportive therapies were according to local institutional practices. We completed the study in six transplantation centres in Canada and two in Australia.\u003c/p\u003e \u003cp\u003eRandomization and masking\u003c/p\u003e \u003cp\u003eWe used minimization\u003csup\u003e10\u003c/sup\u003e to assign patients to either arm A (ATG) or BE (ATG/PTCy). Minimization factors were \u003cem\u003ea priori\u003c/em\u003e risk factors for cGVHD, relapse and mortality, these being participant age (16\u0026ndash;30, 31\u0026ndash;50, \u0026gt; 50); female donor for male recipient; choice of donor (related vs. unrelated); donor age (\u0026thinsp;\u0026lt;\u0026thinsp;=\u0026thinsp;30, 31\u0026ndash;50, \u0026gt;\u0026thinsp;50); disease type; disease risk index; type of preparative regimen, and co-morbidity by augmented HCT-CI; transplant centre was included to balance for differences in support practices.\u003c/p\u003e \u003cp\u003eThe methodology to assign patients to each arm was as follows: The study statistician (T. Panzarella) prepared two randomization lists using a computer random number generator before the study began: 1) a simple randomization list where both treatments occur equally often; this list was only used when the two treatments had equal sums for the levels of the baseline prognostic factors; and 2) a list in which the treatment with the smaller total of patient levels occurs with probability 0.8 while the other treatment occurs with probability 0.2. Allocation occurred centrally by Ozmosis Research Inc. Toronto, Canada, and the process was therefore concealed from staff at the participant\u0026rsquo;s centre. Though the assignment process is not blinded it is objective and can be audited.\u003c/p\u003e \u003cp\u003eTransplant Procedures\u003c/p\u003e \u003cp\u003ePatients in the standard ATG group (A) received rabbit anti-thymocyte globulin (Thymoglobuline, Sanofi\u0026ndash;Genzyme, Lyon, France) intravenously at a total dose of 4.5 mg/kg over 3 days (0.5 mg/kg on day\u0026thinsp;\u0026minus;\u0026thinsp;2, and 2.0 mg/kg on days\u0026thinsp;\u0026minus;\u0026thinsp;1 and +\u0026thinsp;1). The dose was calculated on actual body weight, and no reductions were specified. Dose interruptions for reactions were permitted but it was expected that the entire daily dose would be infused on the same day as initiated. Patients in the experimental group (BE) received ATG as for group A and also received PTCy 50 mg/kg on post-transplant days 3 and 4. All patients received a CNI. Methotrexate 15 mg/m\u003csup\u003e2\u003c/sup\u003e on day\u0026thinsp;+\u0026thinsp;1 and 10 mg/m\u003csup\u003e2\u003c/sup\u003e on days\u0026thinsp;+\u0026thinsp;3, +6, and +\u0026thinsp;11 was added for patients receiving myeloablative conditioning and randomized to group A, but not to those randomized to group BE, who received a CNI alone. Mycophenolate (3 centres) or methotrexate (3 centres) was added to those receiving reduced intensity conditioning and randomized to group A but not to those randomized to group BE who received a CNI alone.\u003c/p\u003e \u003cp\u003eStudy data were collected and entered by site personnel into electronic case report forms (eCRFs) and managed by Ozmosis Inc, Toronto in accordance with national and international regulations and standards. Monitoring was carried out by the Data and Safety Monitoring Committee of Cell Therapy and Transplantation Canada. Adverse events were graded according to Common Terminology Criteria 5.0. Adverse events of specific interest, whether serious or not, also had to be reported, these being veno-occlusive disease, hemorrhagic cystitis, and those reactivations of Epstein-Barr virus (EBV) and cytomegalovirus (CMV) that required treatment according to individual centre protocols. Acute and chronic graft versus host disease were diagnosed and graded by standard criteria\u003csup\u003e11,12\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eSupportive care followed institutional practices except that the use of ganciclovir or foscarnet for primary prophylaxis and the routine use of growth factors, gamma globulin, or alemtuzumab, were not allowed. Letermovir was allowed. Treatment of acute GVHD and chronic GVHD was according to centre preferences. Patients filled out questionnaires related to quality of life and socio-demographics, results from which will be reported separately.\u003c/p\u003e \u003cp\u003eOutcomes\u003c/p\u003e \u003cp\u003eThe study was designed to assess the safety of the experimental arm, prior to consideration of a subsequent efficacy (phase III) trial. The primary safety outcome was mortality, the expectation being that survival in experimental arm BE would be at least 90% that of the standard arm at 100 days post-transplant. Secondary safety endpoints were, incidence of serious infection, incidence of CMV reactivation, time to non-relapse mortality, time to all-cause mortality, incidence of graft rejection or failure, time to disease relapse, time to engraftment, incidence of EBV reactivation and post-transplant lymphoproliferative disorder; secondary efficacy endpoints were incidences of aGVHD and cGVHD, chronic graft versus host disease free- and relapse-free survival (CRFS), need for immunosuppressive therapy (IST) at 12 -months (Yes/No), and quality of life (to be reported separately).\u003c/p\u003e \u003cp\u003eTime to neutrophil engraftment was the time from transplant (Day 0) to the first day of achieving an absolute neutrophil count of 0.5 x 109/L. Time to platelet engraftment was the time from transplant (Day 0) to the first day of achieving a platelet count of greater than 20x109/L without requiring platelet transfusions in the previous 7 days. Primary graft failure was the absence of neutrophil recovery (absolute neutrophil count less than 0.5 x 109/L) in patients surviving until at least Day\u0026thinsp;+\u0026thinsp;28 post-transplant; secondary graft failure was a loss of neutrophil engraftment in the absence of primary disease.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eThe primary analysis was planned according to the intention-to-treat principle; however, a modified intention-to-treat population was used. A small number of participants who were randomized but subsequently found to be ineligible were excluded and did not undergo follow-up. All remaining participants were analyzed according to their randomized treatment assignment.\u003c/p\u003e \u003cp\u003eBecause immune marker levels and time to neutrophil engraftment exhibited skewed distributions, comparisons between treatment groups were performed using the Wilcoxon rank-sum test. Proportions between the two treatment groups were compared using Fisher\u0026rsquo;s exact test.\u003c/p\u003e \u003cp\u003eTime-to-event endpoints were calculated from the date of transplantation using the Kaplan\u0026ndash;Meier method or, when competing risks were present, the cumulative incidence (CI) method. Between-group differences were assessed using the log-rank test or Gray\u0026rsquo;s test, respectively.\u003c/p\u003e \u003cp\u003eOverall survival was defined as the time from transplantation to death from any cause or, for surviving participants, to the date of last follow-up. Relapse-free survival was defined as the time to relapse or death, whichever occurred first. Chronic graft-versus-host disease (GVHD)\u0026ndash; and relapse-free survival was defined as the time to the earliest of the following events: (1) moderate or severe chronic GVHD, (2) relapse, or (3) death.\u003c/p\u003e \u003cp\u003eFor analyses of non-relapse-related mortality (NRM), relapse-related death was treated as a competing risk; for time to relapse, death from other cause was treated as a competing event. For acute GVHD, death was considered a competing risk. In analyses of Grade II\u0026ndash;IV acute GVHD, Grade I events were censored at the last follow-up; similarly, in analyses of Grade III\u0026ndash;IV acute GVHD, Grades I and II events were censored.\u003c/p\u003e \u003cp\u003eAll analyses were conducted using SAS version 9.4 (SAS Institute Inc., Cary, NC) in SAS Studio.\u003c/p\u003e \u003cp\u003eFunding source and sponsorship\u003c/p\u003e \u003cp\u003eThis trial was sponsored by McMaster University, Hamilton, Ontario, Canada, registered at clinicaltrials.gov (NCT04202835) on November 29, 2019, and funded by Sanofi. This was an investigator-initiated study and Sanofi had no role in study design, data collection, data analysis, data interpretation, or writing of the report. Trial management was by Ozmosis Research Inc. Toronto, Canada. Authors had no conflicts of interest other than for the above funding from Sanofi, the manufacturer of ATG (Thymoglobulin), which was administered equally in both arms of the trial.\u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003cp\u003eThe study database was locked after all patients had been followed for at least 12 months, at which time median follow up of living patients was 24.1 months (range 11.89- 26.71) and 23.7 months (range 11.99-25.07) for arms A and BE respectively.\u0026nbsp;\u0026nbsp;Our intention was to transplant 80 eligible patients. \u0026nbsp;Between October 26th, 2020, and February 7th, 2024, we randomly assigned 85 patients (Figure 1), six of whom were excluded leaving 79 patients available for analysis. \u0026nbsp;Of the six patients, five were found to be ineligible and one had his/her transplantation cancelled. \u0026nbsp;Forty patients were analyzed from arm A (ATG alone) and 39 patients from experimental arm BE (ATG/PTCy). \u0026nbsp;Baseline characteristics did not differ between the treatment groups (Table 1).\u0026nbsp;\u0026nbsp;Median age was 59 years, range 19-74 with males 59.5%. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eOutcomes at 100 days following transplantation, the primary endpoint.\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eResults, all at day 100, are summarized in Table 2. \u0026nbsp;Thirty-eight (38) of 40 patients (95.0%) in arm A and thirty-seven (37) of 39 patients (94.9%) in arm BE survived to 100 days (primary endpoint; p\u0026gt;0.9). In arm A, deaths were due to cardiac arrest (n=1) and subdural hematoma (n=1); in arm BE, deaths were due to acute respiratory distress syndrome (n=1) and post-transplant lymphoproliferative disorder (n=1). \u0026nbsp;Acute graft-versus-host disease occurred in 15 patients in arm A and 6 in arm BE (p=0.041). Grades II–IV AGVHD were reported in 6 and 3 patients (p=0.49), and grades III–IV in 3 and 0 patients (p=0.24), in arms A and BE. At day 100, two patients in each arm were receiving systemic corticosteroids. Serious adverse events were reported in 26 patients (65.0%) in arm A and 25 patients (64.1%) in arm BE (p\u0026gt;0.9).\u003c/p\u003e\n\u003cp\u003eGraft failure at 28 days (standard criteria), occurred in 3 patients in arms A and 1 patient in arm BE (p=0.62),\u0026nbsp;with all 4 patients achieving engraftment by 56 days. Median time to neutrophil engraftment was 19 days (range, 10–45) in arm A and 22 days (range, 15–56) in arm BE (p=0.007). Cytomegalovirus reactivation requiring treatment occurred in 11 patients in arm A and 6 in arm BE (p=0.45), while Epstein–Barr virus reactivation occurred in 7 and 5 patients (p\u0026gt;0.9), respectively. \u0026nbsp;Median CD4 counts were 63 cells/mm (IQR = interquartile range 40.0-125.0) in arm A and 59.5 (IQR 28.5-137.5) in arm BE (p=0.58). \u0026nbsp; Median serum IgG levels were 740 mg/dL(IQR 629-850) in arm A and 620 (IQR 550-794) in arm BE (p=0.16). \u0026nbsp;Median CD8 levels were 190 cells/mm\u003csup\u003e3\u003c/sup\u003e (IQR 55-390) in arm A and 240 (IQR 70-473) in arm BE (p=0.42). \u0026nbsp;Complete immune marker results at 100 days, together with results at one year, are summarized in Table 3 and there were no statistically significant differences between the arms.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eOutcomes at long-term follow-up\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eAfter a median follow up of 23.9 months (range 11.89-26.71), 53 patients remained alive and their data was analyzed. \u0026nbsp;The major endpoints are summarized and illustrated in Table 4 and Figure 2 (A-D). Overall survival (Figure 2A) at 12-months was 72.5% (% SE 7.1) in arm A and 75.8% (SE 7.0) in arm BE (p=0.79). \u0026nbsp;Cumulative incidence of NRM at 6-months (Figure 2B) was 7.5% (SE 4.2) in arm A and 8.0% (SE 4.) in arm BE (Gray’s test p=0.45). \u0026nbsp;Relapses were seen in 8 patients in each arm. \u0026nbsp;Cumulative incidence of relapse at 6-months (Figure 2C) was 15.0% (SE 5.7) in arm A and 15.7% (SE 6.0) in arm BE (Gray’s test p=0.88). \u0026nbsp; Relapse-free survival at 12-months was 60.0% (SE 7.8) in arm A and 65.9% (SE 7.7) in arm BE (log rank p=0.66). \u0026nbsp; Moderate or severe chronic GVHD- and relapse-free survival (CRFS; Figure 2D) at 12-months was 56.1% (SE 7.8) in arm A and 60.6% (SE 7.9) in arm BE (log rank p=0.69). \u0026nbsp;Acute GVHD (all grades) was seen in 18 patients in arm A and 18 patients in arm BE, and CI at 6-months was 42.5% (SE 8.0) in arm A and 23.7% (SE 7.0) in arm BE (Gray’s test p=0.04). \u0026nbsp;Acute GVHD Grades II-IV were seen in 11 in arm A and 5 patients in arm BE, and CI at 6-months was 25.0% (SE7.0) in arm A and 13.1% (SE 5.6) in arm BE, (Gray’s test p=0.13), and grade III/IV in 5 patients in arm A and 1 patient in arm BE, CI at 6-months 10.0 (SE 4.8) and 2.7% (SE 2.7), Gray’s test p=0.10) in arms A and BE respectively. \u0026nbsp;Late AGVHD (after day 100) occurred in 3 patients in each arm. \u0026nbsp;CGVHD has been reported to date in 6 patients and 3 patients in arms A and BE respectively with moderate or severe grades in 2 patients in each arm. \u0026nbsp;Steroid and/or immunosuppressive agents were being administered at 12 months by 6 patients and 2 patients in arms A and BE respectively. \u0026nbsp;\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThis randomized pilot trial, intended to assess the safety of ATG/PTCy when compared with standard ATG, achieved its primary endpoint of survival in the ATG/PTCy arm being at least 90% of that in the ATG arm, at 100 days. \u0026nbsp;A variety of secondary safety endpoints showed no excess toxicity in the experimental arm (ATG/PTCy), nor, after minimal follow up of 24 months, adverse effects on survival, rate of infections or rate of disease relapse. \u0026nbsp; Time to completed accrual to this trial was much longer than intended, due to staffing and administrative complications of the COVID era; a benefit was a longer than intended follow-up period, allowing assessment of longer-term outcomes supporting the 100-day observations, pointing to safety of the combined approach. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eA weakness of this study is defining safety under a limited primary endpoint of short-term survival. \u0026nbsp; Survival may be an insensitive measure of safety given that there are a wide variety of potential toxicities that would also be unacceptable for further use of the experimental treatment (ATG/PTCy). \u0026nbsp;We considered, however, that a primary endpoint based on a variety of toxicities would be difficult to define, and debatable, while a decrease of survival would provide an undebatable end to further investigation of the experimental treatment. \u0026nbsp; Nevertheless, the concept of safety in this trial is well supported by a variety of secondary endpoints describing the well-known complications of bone marrow transplantation. \u0026nbsp;The choice of 100 days relates to the span of time during which most transplant-related toxicities occur but the results at long term follow up also point to safety.\u003c/p\u003e\n\u003cp\u003eWe consider, based on results in this trial, in particular those pointing to safety and the trend in the incidence of acute GVHD, \u0026nbsp;together with the already widespread use of the combination\u003csup\u003e13,14\u003c/sup\u003e, that PTCy/ATG is sufficiently safe to be further investigated for the prevention of GVHD in a large randomized trial sufficiently powered to assess incidences of acute and chronic GVHD.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eCorresponding author:\u003c/strong\u003e\u0026nbsp; \u0026nbsp;Irwin Walker [email protected]\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions:\u003c/strong\u003e IW, TP and KP designed the study; TP performed the analysis; correlative studies were conducted by KRS (biological markers of GVHD) and JS (ATG pharmacokinetics); Elsawy guided quality of life studies; all authors reviewed the draft and contributed to the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRegistration:\u0026nbsp;\u003c/strong\u003eclinicaltrials.gov (NCT04202835), November 29, 2019\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e\u0026nbsp; This study was funded by Sanofi as an investigator-initiated trial, being conducted at arm’s length, with Sanofi not contributing to the design, conduct, analysis or final manuscript. The Desroches Bone Marrow Transplant Fund, McMaster University, Hamilton, Canada, provided funding for protocol development.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData sharing:\u003c/strong\u003e\u0026nbsp; No clinical trial data has been shared outside of the authors and coordinating centre. The trial protocol will be made available on request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDisclosures:\u003c/strong\u003e\u0026nbsp; All authors received research funds from Sanofi, either directly or indirectly. \u0026nbsp; There are no other relevant disclosures.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics statement:\u0026nbsp;\u003c/strong\u003eThe study was conducted in accordance with the Declaration of Helsinki and was approved by Clinical Trials Ontario (CTO Stream #1852) and by ethics committees at participating centres. \u0026nbsp; Written informed consent was obtained from all participants prior to their enrollment in the study. \u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBacigalupo A. Lamparelli T. Barisione G. Bruzzi P. Guidi S. Alessandrino PE. di Bartolomeo P. Oneto R. Bruno B. Sacchi N. van Lint MT. Bosi A. Gruppo Italiano Trapianti Midollo Osseo (GITMO). Thymoglobulin prevents chronic graft-versus-host disease, chronic lung dysfunction, and late transplant-related mortality: long-term follow-up of a randomized trial in patients undergoing unrelated donor transplantation. \u003cem\u003eBiol Blood Marrow Transplant\u003c/em\u003e. 2006;12(5):560-565.\u003c/li\u003e\n\u003cli\u003eFinke J, Schmoor C, Bethge WA, et al. Long-term outcomes after standard graft-versus-host disease prophylaxis with or without anti-human-T-lymphocyte immunoglobulin in haemopoietic cell transplantation from matched unrelated donors: final results of a randomised controlled trial. \u003cem\u003eThe LancetHaematology\u003c/em\u003e. 2017;4(6):e293-e301.\u003c/li\u003e\n\u003cli\u003eWalker I, Panzarella T, Couban S, et al. Addition of anti-thymocyte globulin to standard graft-versus-host disease prophylaxis versus standard treatment alone in patients with haematological malignancies undergoing transplantation from unrelated donors: final analysis of a randomised, open-label, multicentre, phase 3 trial. \u003cem\u003eLancet Haematol\u003c/em\u003e. Published online January 2020:S2352302619302200. doi:10.1016/S2352-3026(19)30220-0\u003c/li\u003e\n\u003cli\u003eSoiffer RJ, Kim HT, McGuirk J, et al. Prospective, Randomized, Double-Blind, Phase III Clinical Trial of Anti\u0026ndash;T-Lymphocyte Globulin to Assess Impact on Chronic Graft-Versus-Host Disease\u0026ndash;Free Survival in Patients Undergoing HLA-Matched Unrelated Myeloablative Hematopoietic Cell Transplantation. \u003cem\u003eJ Clin Oncol\u003c/em\u003e. 2017;35(36):4003-4011. doi:10.1200/JCO.2017.75.8177\u003c/li\u003e\n\u003cli\u003eChang YJ, Wu DP, Lai YR, et al. Antithymocyte Globulin for Matched Sibling Donor Transplantation in Patients With Hematologic Malignancies: A Multicenter, Open-Label, Randomized Controlled Study. \u003cem\u003eJ Clin Oncol\u003c/em\u003e. Published online July 10, 2020:JCO.20.00150. doi:10.1200/JCO.20.00150\u003c/li\u003e\n\u003cli\u003eBola\u0026ntilde;os-Meade J, Hamadani M, Wu J, et al. Post-Transplantation Cyclophosphamide-Based Graft-versus-Host Disease Prophylaxis. \u003cem\u003eN Engl J Med\u003c/em\u003e. 2023;388(25):2338-2348. doi:10.1056/NEJMoa2215943\u003c/li\u003e\n\u003cli\u003eCurtis DJ, Patil SS, Reynolds J, et al. Graft-versus-Host Disease Prophylaxis with Cyclophosphamide and Cyclosporin. \u003cem\u003eN Engl J Med\u003c/em\u003e. Published online June 13, 2025:NEJMoa2503189. doi:10.1056/NEJMoa2503189\u003c/li\u003e\n\u003cli\u003eLuznik L, Pasquini MC, Logan B, et al. Randomized Phase III BMT CTN Trial of Calcineurin Inhibitor\u0026ndash;Free Chronic Graft-Versus-Host Disease Interventions in Myeloablative Hematopoietic Cell Transplantation for Hematologic Malignancies. \u003cem\u003eJ Clin Oncol\u003c/em\u003e. 2022;40(4):356-368. doi:10.1200/JCO.21.02293\u003c/li\u003e\n\u003cli\u003eXu ZL, Han TT, Zhu XL, et al. Randomized trial of anti-thymocyte globulin plus lowdose post-transplant cyclophosphamide to prevent graft-versus- host disease in haploidentical transplantation. \u003cem\u003eHaematologica\u003c/em\u003e. 2025;110(12):2965-2973. doi:10.3324/haematol.2025.287504\u003c/li\u003e\n\u003cli\u003eScott NW, McPherson GC, Ramsay CR, Campbell MK. The method of minimization for allocation to clinical trials. a review. \u003cem\u003eControl Clin Trials\u003c/em\u003e. 2002;23(6):662-674.\u003c/li\u003e\n\u003cli\u003eHarris AC, Young R, Devine S, et al. International, Multicenter Standardization of Acute Graft-versus-Host Disease Clinical Data Collection: A Report from the Mount Sinai Acute GVHD International Consortium. \u003cem\u003eBiol Blood Marrow Transplant J Am Soc Blood Marrow Transplant\u003c/em\u003e. 2016;22(1):4-10. doi:10.1016/j.bbmt.2015.09.001\u003c/li\u003e\n\u003cli\u003eJagasia MH, Greinix HT, Arora M, et al. National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2014 Diagnosis and Staging Working Group Report. \u003cem\u003eBiol Blood Marrow Transplant J Am Soc Blood Marrow Transplant\u003c/em\u003e. 2014;(Journal Article). doi:10.1016/j.bbmt.2014.12.001;\u003c/li\u003e\n\u003cli\u003eDeZern A, Zahurak ML, Symons HJ, et al. Alternative donor BMT with post-transplant cyclophosphamide as initial therapy for acquired severe aplastic anemia. \u003cem\u003eBlood J\u003c/em\u003e. Published online April 21, 2023:blood.2023020435. doi:10.1182/blood.2023020435\u003c/li\u003e\n\u003cli\u003eDul\u0026eacute;ry R, Brissot E, Mohty M. Combining post-transplant cyclophosphamide with antithymocyte globulin for graft-versus-host disease prophylaxis in hematological malignancies. \u003cem\u003eBlood Rev\u003c/em\u003e. 2023;62:101080. doi:10.1016/j.blre.2023.101080\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1. \u0026nbsp;Patient characteristics according to minimization factors.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"576\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 288px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFactor\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003eStandard Arm A\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eATG\u003c/p\u003e\n \u003cp\u003eN (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003eExperimental Arm BE\u003c/p\u003e\n \u003cp\u003eATG + PTCy\u003c/p\u003e\n \u003cp\u003eN (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 288px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e39\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 288px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePatient Age\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 288px;\"\u003e\n \u003cp\u003e16 \u0026ndash; 30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e3 (7.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e2 (5.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 288px;\"\u003e\n \u003cp\u003e31 \u0026ndash; 50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e10 (25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e12 (30.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 288px;\"\u003e\n \u003cp\u003e\u0026gt; 50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e27 (67.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e25 (64.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 288px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFemale donor for male recipient\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 288px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e7 (17.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e6 (15.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 288px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e33 (82.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e33 (84.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 288px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDisease type\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 288px;\"\u003e\n \u003cp\u003eMDS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e12 (30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e12 (30.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 288px;\"\u003e\n \u003cp\u003eAML\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e28 (70)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e27 (69.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 288px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eChoice of donor\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 288px;\"\u003e\n \u003cp\u003eRelated\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e14 (35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e14 (35.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 288px;\"\u003e\n \u003cp\u003eUnrelated\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e26 (65)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e25 (64.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 288px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDonor Age\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 288px;\"\u003e\n \u003cp\u003e\u0026le; 30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e19 (47.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e17 (43.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 288px;\"\u003e\n \u003cp\u003e31 \u0026ndash; 50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e11 (27.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e12 (30.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 288px;\"\u003e\n \u003cp\u003e\u0026gt; 50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e10 (25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e10 (25.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 288px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eType of preparative regimen\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 288px;\"\u003e\n \u003cp\u003eMyeloablative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e27 (67.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e22 (56.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 288px;\"\u003e\n \u003cp\u003eReduced Intensity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e13 (32.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e17 (43.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 288px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDisease risk index\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 288px;\"\u003e\n \u003cp\u003eVery high\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e1 (2.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 288px;\"\u003e\n \u003cp\u003eHigh\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e12 (30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e12 (30.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 288px;\"\u003e\n \u003cp\u003eIntermediate\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e23 (57.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e24 (61.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 288px;\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e5 (12.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e2 (5.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 288px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCo-morbidity by augmented HCT-Cl\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 288px;\"\u003e\n \u003cp\u003e0 \u0026ndash; 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e27 (67.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e25 (64.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 288px;\"\u003e\n \u003cp\u003e\u0026gt; 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e13 (32.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e14 (35.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 288px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSite\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 288px;\"\u003e\n \u003cp\u003eCancer Care Manitoba\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e3 (7.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e3 (7.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 288px;\"\u003e\n \u003cp\u003eHamilton Health Sciences \u0026ndash; Juravinski Cancer Centre\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e18 (45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e17 (43.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 288px;\"\u003e\n \u003cp\u003eUniversity Hospital \u0026ndash; London Health Sciences Centre\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e7 (17.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e6 (15.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 288px;\"\u003e\n \u003cp\u003eSaskatoon Cancer Centre\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e2 (5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e1 (2.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 288px;\"\u003e\n \u003cp\u003eCHU de Quebec-Hopital l\u0026rsquo;Enfant-Jesus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e2 (5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e3 (7.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 288px;\"\u003e\n \u003cp\u003eSaint Vincent\u0026rsquo;s Hospital\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e1 (2.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e1 (2.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 288px;\"\u003e\n \u003cp\u003eRoyal North Shore Hospital\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e2 (5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e2 (5.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 288px;\"\u003e\n \u003cp\u003eQEII Health Sciences Centre\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e5 (12.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e6 (15.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eTable 2. \u0026nbsp;Summary of outcomes at 100 days post transplantation. \u0026nbsp; Results of all immune markers at 100 days and one year are seen in table 3.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"623\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 264px;\"\u003e\n \u003cp\u003eArm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003eArm A\u003c/p\u003e\n \u003cp\u003eATG\u003c/p\u003e\n \u003cp\u003eN (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003eArm BE\u003c/p\u003e\n \u003cp\u003eATG+PTCy\u003c/p\u003e\n \u003cp\u003eN (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003ep-value\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 264px;\"\u003e\n \u003cp\u003eSubjects\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 264px;\"\u003e\n \u003cp\u003eSurvival to 100 days\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e38 (95.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e37 (94.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026gt;0.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 264px;\"\u003e\n \u003cp\u003eSubjects with SAEs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e26 (65.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e25 (64.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026gt;0.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 264px;\"\u003e\n \u003cp\u003eAGVHD grades I-IV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e15 (37.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e6 (15.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003e0.041\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 264px;\"\u003e\n \u003cp\u003eGrade II-IV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e6 (15.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e3 (7.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003e0.49\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 264px;\"\u003e\n \u003cp\u003eGrade III-IV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e3 (7.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e0 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003e0.24\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 264px;\"\u003e\n \u003cp\u003eNeutrophil engraftment days (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e19 (10-45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e22 (15-56)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003e0.007\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 264px;\"\u003e\n \u003cp\u003eGraft failure at 28 days\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e3 (7.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e1(2.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003e0.62\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 264px;\"\u003e\n \u003cp\u003eCMV reactivation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e11 (27.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e7 (17.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003e0.45\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 264px;\"\u003e\n \u003cp\u003eEBV reactivation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e6 (15.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e5 (12.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003e0.29\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 264px;\"\u003e\n \u003cp\u003eSteroid use at 100 days\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e2 (5.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e2 (5.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026gt;0.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eTable 3. \u0026nbsp;Immune marker (CD4, CD8, IgG) levels at Day 100 and One Year. \u0026nbsp;IQR=interquartile range.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 116px;\"\u003e\n \u003cp\u003eArm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 84px;\"\u003e\n \u003cp\u003eCD4\u003c/p\u003e\n \u003cp\u003e(Day 100)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 74px;\"\u003e\n \u003cp\u003eCD8\u003c/p\u003e\n \u003cp\u003e(Day 100)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003eIgG\u003c/p\u003e\n \u003cp\u003e(Day 100)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eCD4\u003c/p\u003e\n \u003cp\u003e(1 Year)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003eCD8\u003c/p\u003e\n \u003cp\u003e(1 Year)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 73px;\"\u003e\n \u003cp\u003eIgG\u003c/p\u003e\n \u003cp\u003e(1 Year)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 116px;\"\u003e\n \u003cp\u003eStandard Arm ATG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003eMedian\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 84px;\"\u003e\n \u003cp\u003e63\u003c/p\u003e\n \u003cp\u003e(n=34)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 74px;\"\u003e\n \u003cp\u003e190\u003c/p\u003e\n \u003cp\u003e(n=33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003e740\u003c/p\u003e\n \u003cp\u003e(n=35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003e140\u003c/p\u003e\n \u003cp\u003e(n=28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e317\u003c/p\u003e\n \u003cp\u003e(n=28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 73px;\"\u003e\n \u003cp\u003e773\u003c/p\u003e\n \u003cp\u003e(n=28)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 116px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003eIQR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 84px;\"\u003e\n \u003cp\u003e40-125\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 74px;\"\u003e\n \u003cp\u003e55-390\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003e629-850\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003e106-270\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e170-731\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 73px;\"\u003e\n \u003cp\u003e534-1045\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 116px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 84px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 74px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 73px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 116px;\"\u003e\n \u003cp\u003eExperimental Arm ATG + PTCy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003eMedian\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 84px;\"\u003e\n \u003cp\u003e59.5\u003c/p\u003e\n \u003cp\u003e(n=28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 74px;\"\u003e\n \u003cp\u003e240\u003c/p\u003e\n \u003cp\u003e(n=28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003e620\u003c/p\u003e\n \u003cp\u003e(n=29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003e190\u003c/p\u003e\n \u003cp\u003e(n=22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e378.5\u003c/p\u003e\n \u003cp\u003e(n=22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 73px;\"\u003e\n \u003cp\u003e920\u003c/p\u003e\n \u003cp\u003e(n=21)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 116px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003eIQR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 84px;\"\u003e\n \u003cp\u003e29-138\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 74px;\"\u003e\n \u003cp\u003e70-473\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003e550-794\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003e140-271\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e197-890\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 73px;\"\u003e\n \u003cp\u003e700-992\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 116px;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e\n \u003cp\u003e(Wilcoxon rank-sum test)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 84px;\"\u003e\n \u003cp\u003e0.58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 74px;\"\u003e\n \u003cp\u003e0.42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003e0.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003e0.48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 73px;\"\u003e\n \u003cp\u003e0.51\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cu\u003eNormal ranges\u003c/u\u003e:\u0026nbsp;CD4: 500-1200 cells/mm\u003csup\u003e3\u003c/sup\u003e\u0026nbsp; \u0026nbsp;CD8:\u0026ensp;150-1000 cells/mm\u003csup\u003e3\u0026nbsp;\u003c/sup\u003e\u0026nbsp; IgG:\u0026ensp;600-1640 mg/dL\u003c/p\u003e\n\u003cp\u003eTable 4. \u0026nbsp;Overall results at long term follow up.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"600\" class=\"fr-table-selection-hover\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 288px;\"\u003e\n \u003cp\u003eArm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 116px;\"\u003e\n \u003cp\u003eArm A\u003c/p\u003e\n \u003cp\u003eATG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003eArm BE\u003c/p\u003e\n \u003cp\u003eATG+PTCy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 73px;\"\u003e\n \u003cp\u003ep-value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 288px;\"\u003e\n \u003cp\u003eSubjects living\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 116px;\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 73px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 288px;\"\u003e\n \u003cp\u003eMedian FU (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 116px;\"\u003e\n \u003cp\u003e24.1 (11.89, 26.71)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003e23.7 (11.99, 25.07)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 73px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 288px;\"\u003e\n \u003cp\u003eTime to Relapse (CI%, 6 mths, SE)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 116px;\"\u003e\n \u003cp\u003e15.0 (5.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003e15.7 (6.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 73px;\"\u003e\n \u003cp\u003e0.88\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 288px;\"\u003e\n \u003cp\u003eRelapse-Free Survival (%,12 mths, SE)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 116px;\"\u003e\n \u003cp\u003e60.0 (7.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003e65.9 (7.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 73px;\"\u003e\n \u003cp\u003e0.66\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 288px;\"\u003e\n \u003cp\u003eTime to NRM (CI%, 6mths, SE)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 116px;\"\u003e\n \u003cp\u003e7.5 (4.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003e8.0 (4.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 73px;\"\u003e\n \u003cp\u003e0.45\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 288px;\"\u003e\n \u003cp\u003eOverall Survival (%, 12 mths, SE)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 116px;\"\u003e\n \u003cp\u003e72.5 (7.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003e75.8 (7.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 73px;\"\u003e\n \u003cp\u003e0.79\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 288px;\"\u003e\n \u003cp\u003eCRFS (12 mths, %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 116px;\"\u003e\n \u003cp\u003e56.1%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003e60.6%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 73px;\"\u003e\n \u003cp\u003e0.69\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"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":"bone-marrow-transplantation","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"bmt","sideBox":"Learn more about [Bone Marrow Transplantation](http://www.nature.com/bmt/)","snPcode":"41409","submissionUrl":"https://mts-bmt.nature.com/cgi-bin/main.plex","title":"Bone Marrow Transplantation","twitterHandle":"@bmtjournal","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-8949910/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8949910/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eIn a randomized pilot trial we compared ATG (standard Arm A, 4.5 mg/kg) with ATG plus PTCy (experimental Arm BE, ATG 4.5 mg/kg, PTCy 100 mg/kg). The primary safety endpoint was overall survival at 100 days. We analyzed 79 patients with AML (n=55) or MDS (n=24). Median age (range) was 59 (19 to 74), 47 (59.5 %) were male. Conditioning was either myeloablative (n=49) or reduced intensity (n=30). Donors were 8/8 HLA-matched. \u0026nbsp;Overall survival at 100 days was 95.0% (37 of 39 patients) vs 94.9% (38 of 40 patients) in arm A vs arm BE (p\u0026gt;0.9). In arms A versus BE, serious adverse events (SAEs) occurred in 26 (65.0%) and 25 (64.1%) patients, graft failure occurred in 3 and 1 patients (p\u0026gt;0.9), median (range) days to neutrophil engraftment were 19 (10-45) versus 22 (15-56) days p=0.007), cytomegalovirus and Epstein-Barr virus reactivations occurred in 11 and 7 patients (p=0.45) and in 6 and 5 patients (p=0.29). Overall survival at 12-months was 72.5% versus 75.8% (p-0.79), cumulative incidence at 6 months of relapse was 15.0% versus 15.7% (p=0.88) and of non-relapse mortality (NRM) 7.5% versus 8.0 (p=0.45). The combination of ATG and PTCy can safely be used in phase III trials.\u003c/p\u003e","manuscriptTitle":"A Randomized Pilot Trial comparing Anti-Thymocyte Globulin (ATG) with ATG plus Post Transplant Cyclophosphamide (PTCy) for Prophylaxis against Acute and Chronic Graft Versus Host Disease (GVHD) in Matched Donor Hematopoietic Cell Transplants (HCT)","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-13 18:12:58","doi":"10.21203/rs.3.rs-8949910/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"revise","date":"2026-04-30T09:06:09+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"This content is not available.","date":"2026-03-24T16:49:41+00:00","index":3,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2026-03-14T09:15:46+00:00","index":3,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2026-03-10T11:11:01+00:00","index":2,"fulltext":"This content is not available."},{"type":"editorInvitedReview","content":"This content is not available.","date":"2026-03-10T10:51:12+00:00","index":1,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2026-03-10T09:57:20+00:00","index":1,"fulltext":"This content is not available."},{"type":"reviewersInvited","content":"","date":"2026-03-10T07:00:51+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-02-27T17:03:57+00:00","index":"","fulltext":""},{"type":"submitted","content":"Bone Marrow Transplantation","date":"2026-02-27T16:36:26+00:00","index":"","fulltext":""},{"type":"checksFailed","content":"","date":"2026-02-24T16:12:26+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-02-23T18:33:30+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bone-marrow-transplantation","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"bmt","sideBox":"Learn more about [Bone Marrow Transplantation](http://www.nature.com/bmt/)","snPcode":"41409","submissionUrl":"https://mts-bmt.nature.com/cgi-bin/main.plex","title":"Bone Marrow Transplantation","twitterHandle":"@bmtjournal","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"5674cd8e-0875-4457-8c3f-88f00d53a2cd","owner":[],"postedDate":"March 13th, 2026","published":true,"recentEditorialEvents":[{"type":"decision","content":"revise","date":"2026-04-30T09:06:09+00:00","index":"","fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"in-revision","subjectAreas":[{"id":64478791,"name":"Health sciences/Medical research/Clinical trial design/Randomized controlled trials"},{"id":64478792,"name":"Health sciences/Medical research/Stem-cell research"}],"tags":[],"updatedAt":"2026-04-30T09:10:36+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-13 18:12:58","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8949910","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8949910","identity":"rs-8949910","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}