Impact of prior solid tumors and their treatment modality on outcomes after allogeneic hematopoietic stem cell transplantation: A KSGCT multi-center retrospective study

Impact of prior solid tumors and their treatment modality on outcomes after allogeneic hematopoietic stem cell transplantation: A KSGCT multi-center retrospective study | 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 Impact of prior solid tumors and their treatment modality on outcomes after allogeneic hematopoietic stem cell transplantation: A KSGCT multi-center retrospective study Keisuke Kataoka, Takayuki Fujii, Masatoshi Sakurai, Hiroaki Shimizu, and 26 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6595951/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 15 Sep, 2025 Read the published version in Bone Marrow Transplantation → Version 1 posted 10 You are reading this latest preprint version Abstract Despite the increasing number of cancer survivors, the impact of prior solid tumors and their treatment modality on outcomes after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains unclear. This multi-center retrospective study compared transplant outcomes in allo-HSCT recipients with and without a history of solid tumors. Of 5,850 adult patients who underwent first allo-HSCT, 303 (5.2%) had a prior solid tumor. After propensity score matching, overall survival (OS) and cumulative incidences of relapse, non-relapse mortality (NRM), and acute and chronic graft-versus-host diseases were almost comparable between the two groups. Progression or recurrence of solid tumors after allo-HSCT occurred in only eight cases (2.8%). Importantly, patients who received both chemotherapy and radiation therapy (Chemo + RT) for prior solid tumors had significantly worse OS (35.3% vs. 54.1% [ P < 0.001] vs. 56.8% [ P < 0.001] at 2 years) and higher NRM (36.2% vs. 18.7% [ P = 0.002] vs. 19.3% [ P = 0.001] at 2 years) compared to patients who received other treatment modalities for prior solid tumors or patients without prior solid tumors. These findings highlight the feasibility of allo-HSCT in selected patients with prior solid tumors, while demonstrating the negative impact of Chemo + RT on outcomes after allo-HSCT. Biological sciences/Cancer/Haematological cancer Biological sciences/Stem cells/Haematopoietic stem cells Figures Figure 1 Figure 2 Introduction Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a well-established and potentially curative treatment for various hematologic disorders, including hematologic malignancies and bone marrow failure syndromes. 1 , 2 Although advances in transplantation techniques have improved the safety and efficacy of allo-HSCT, it remains associated with significant morbidity and mortality, including infections, conditioning-related toxicities, and graft-versus-host disease (GVHD), even in patients who do not experience relapse. 3 , 4 Therefore, eligibility for allo-HSCT should be carefully assessed based on disease status, age, PS, comorbidities, and donor availability. 1 , 2 The incidence of cancers is increasing worldwide, and it is currently estimated that approximately one in five individuals will develop cancer during their lifetime. 5 With the advances in cancer treatment, the number of cancer survivors is also increasing. Furthermore, chemotherapy and/or radiation therapy for solid tumors can increase the risk of developing hematologic malignancies, particularly myeloid neoplasms. 6 – 8 These facts result in an increasing number of patients with a history of solid tumors undergoing allo-HSCT. 9 , 10 Such patients are thought to have a higher risk of non-relapse mortality (NRM), as represented by the hematopoietic cell transplantation-specific comorbidity index (HCT-CI), which is the most widely used scoring system for risk assessment of patients undergoing allo-HSCT. 11 – 13 In this score, a history of solid tumor (excluding non-melanoma skin cancer) is given the highest weight of 3 points, along with heart valve disease, severe pulmonary dysfunction, and moderate to severe hepatic dysfunction, based on hazard ratios (HR) for 2-year NRM. 11 Patients with solid tumors undergo various treatment modalities, including surgery, endoscopic resection, chemotherapy, radiation therapy, and molecularly targeted agents. In addition to progression and/or recurrence of solid tumors, prior treatment for solid tumors may contribute to the increased risk of NRM through inducing tissue damage. However, the effect of different treatment modalities on NRM remains unknown. In addition, the incidences of solid tumor types vary by race and country, 14 and these differences in tumor distribution and treatment approaches may influence the effect of prior solid tumors on transplant outcomes. It is well known that factors such as conditioning regimens, GVHD, its prophylaxis and treatment, and delayed hematopoietic recovery can cause immunosuppression in allo-HSCT recipients. 3 , 15 , 16 This immunosuppression raises concerns about an increased risk of the progression and/or recurrence of solid tumors, but the consequences of prior solid tumors after allo-HSCT have not been well investigated. Overall, determining the eligibility for allo-HSCT in patients with hematologic disorders who have a history of solid tumors is challenging in the real world. To address these issues, this study evaluated the impact of a history of solid tumors and their treatment modalities on transplant outcomes in allo-HSCT recipients and clarified the consequences of prior solid tumors after transplantation using a large-scale Japanese database. Methods Study design and data source This study is a retrospective cohort analysis of adult patients aged ≥ 16 years undergoing first allo-HSCT between 2010 and 2022 at 20 institutions participating in the Kanto Study Group for Cell Therapy (KSGCT). Data were collected from the KSGCT database. Detailed information on prior solid tumors was collected through a secondary survey, including tumor type, stage, date of diagnosis, treatment modalities, response (complete remission [CR], partial remission [PR], stable disease [SD], and progressive disease) at the time of transplantation, and the presence and timing of progression or recurrence. Non-melanoma skin cancers were excluded from prior solid tumors according to the HCT-CI definition. 11 Patients who developed therapy-related myeloid neoplasms (t-MN) following treatment for a prior hematologic malignancy were excluded. This study was conducted in accordance with the Declaration of Helsinki and was approved by the ethics committee of Keio University School of Medicine (Tokyo, Japan) (approval number 20231134). Definition Acute and chronic GVHD were diagnosed and graded using established criteria. 17 , 18 Conditioning regimens were classified into myeloablative conditioning (MAC) or reduced-intensity conditioning (RIC) based on the criteria of the Center for International Blood and Marrow Transplant Research (CIBMTR). 19 , 20 t-MN was defined as a myeloid neoplasm that developed following chemotherapy and/or radiation therapy for a prior solid tumor. 21 , 22 Standard-risk diseases included acute myeloid leukemia (AML) in first or second CR, acute lymphoblastic leukemia (ALL) in first CR, chronic myeloid leukemia (CML) in chronic/accelerated phase, low-risk myelodysplastic syndrome (MDS), myeloproliferative neoplasms (MPN), lymphomas with CR/PR, and plasma cell neoplasms in CR/very good PR/PR. The remaining hematologic disorders, mainly bone marrow failure syndromes, were classified as others. Treatment modalities for prior solid tumors were classified into radical resection (surgery or endoscopic resection), chemotherapy, radiation therapy, both chemotherapy and radiation therapy (Chemo + RT), and others (molecularly targeted and hormone therapy). Patients who received chemotherapy and/or radiation therapy were classified accordingly, regardless of whether they also underwent surgery or other treatments. Those who received Chemo + RT, either concurrently or sequentially, were classified into the Chemo + RT group. Propensity score matching Propensity score matching (PSM) was performed to balance patients with and without prior solid tumors. 23 , 24 Propensity scores were estimated using logistic regression models. A 1:4 nearest neighbor matching with a fixed caliper width of 0.2 was applied. A standardized mean difference < 0.10 was considered acceptable. 25 Statistical analysis Baseline characteristics were compared using Fisher’s exact and Mann-Whitney U tests. Overall survival (OS) was estimated by the Kaplan-Meier method, and compared using the log-rank test. Multivariable OS analysis was conducted using the Cox proportional hazards regression models. The cumulative incidence of relapse, NRM, and acute and chronic GVHD was estimated considering competing risks. Univariable and multivariable analyses for relapse and NRM were conducted using the Fine and Gray model. All tests were two-sided with P values < 0.05 considered significant. Analyses were conducted using EZR, 26 a graphical user interface for R (The R Foundation for Statistical Computing, Vienna, Austria). Results Patient and transplant characteristics A total of 5,850 patients were initially identified. Among them, 63 patients who developed t-MN following treatment for prior hematologic malignancies were excluded. Of the remaining 5,787 patients, 303 (5.2%) had a history of solid tumors, while 5,484 (94.8%) had no such history (Fig. 1). Patients and transplant characteristics are summarized in Table 1. Patients with a history of solid tumors were older and had a higher proportion of females. They also had a significantly higher prevalence of myeloid malignancies, such as AML and MDS or MPN, with 134 patients (44.2%) being classified as t-MN. The use of RIC was more common in this group. In addition, a higher proportion of these patients underwent allo-HSCT between 2018 and 2022. The characteristics of prior solid tumors in our cohort are detailed in Table 2. Among solid tumor types, breast cancer (24.4%) was the most common. Among patients whose tumor stage information was available, stages 0–I were the most frequent (24.8%). At the time of allo-HSCT, most patients were in CR (89.1%). Regarding the treatment modalities for solid tumors, radical resection was the most common (37.6%), followed by chemotherapy (25.1%). The median time from diagnosis of prior solid tumors to allo-HSCT was 6.0 years. After performing PSM, 277 patients with a history of prior solid tumors were matched with 1,108 patients without such a history (Fig. 1). The two groups were well balanced, with no significant differences in baseline characteristics (supplementary Table 1). The characteristics of patients with a history of prior solid tumors after PSM were similar to those before PSM (supplementary Table 2). Transplant outcomes In 277 patients with prior solid tumors and 1,108 patients without prior solid tumors after PSM, the median follow-up period for survivors was 62 months (range, 0.3–173 months). The 2-year OS rate of patients with prior solid tumors was slightly worse but not significantly different compared to those without prior solid tumors (51.2% [95% CI, 44.8–57.2%] vs. 56.8% [95% CI, 53.7–59.8%], P = 0.116, Fig. 2A). Similarly, the 2-year relapse rate was not significantly different between the two groups (32.9% [95% CI, 27.3–38.6%] vs. 28.8% [95% CI, 26.1–31.6%], P = 0.191, Fig. 2B). The 2-year NRM rate was also comparable (21.5% [95% CI, 16.7–26.7%] vs. 20.2% [95% CI, 17.8–22.7%], P = 0.293, Fig. 2C). In addition, no significant differences were observed in acute and chronic GVHD incidences between the two groups. The 3-month cumulative incidence of grade II-IV acute GVHD was 36.5% (95% CI, 30.8–42.1%) in patients with prior solid tumors and 32.4% (95% CI, 29.6–35.1%) in those without (supplementary Fig. 1A). Similarly, the 2-year cumulative incidence of chronic GVHD was 29.8% (95% CI, 24.4–35.5%) and 31.3% (95% CI, 28.5–34.2%) in the respective groups (supplementary Fig. 1B). Progression and/or recurrence of prior solid tumors Among 290 patients whose follow-up data for prior solid tumors were available, only eight (2.8%) patients experienced progression and/or recurrence of their prior solid tumors after allo-HSCT (Table 3). These solid tumors included head and neck, lung, esophagogastric, gynecologic cancer, and urologic cancer. Among them, four patients had stage I diseases, and four patients received systemic chemotherapy with or without radiation therapy, achieving CR at transplantation. The median time from solid tumor diagnosis to allo-HSCT was 2.9 years. Of six patients with available data, five experienced tumor progression and/or recurrence within two years after transplantation. There were three deaths, including two of progression and/or recurrence of solid tumors and one of relapse of hematologic disorder. Impact of treatment modality for prior solid tumors on transplant outcomes To evaluate the impact of treatment modality for prior solid tumors on transplant outcomes, we compared OS, relapse, and NRM rates among patients who received radical resection, chemotherapy, radiation therapy, Chemo + RT, and other treatment modalities for prior solid tumors (n = 272) and patients without prior solid tumors (n = 1,108). As patients who received radical resection, chemotherapy, radiation therapy, and other treatments showed similar OS, relapse, and NRM rates (Table 4), they were grouped as Others (n = 227) and compared with patients who received Chemo + RT (n = 45). A comparison of patient characteristics revealed a higher proportion of female patients in the Chemo + RT than in the Others (75.6% vs. 51.5%, P = 0.005, supplementary Table 3). In addition, the Chemo + RT group had a significantly greater proportion of breast cancer (57.7% vs. 18.5%, P < 0.001) and contained more tumors with advanced stages (stage II or higher) (40.0% vs. 16.3%, P = 0.002, supplementary Table 4). The 2-year OS rate was significantly worse in the Chemo + RT at 35.3% (95% CI, 20.9–50.1%) compared to 54.1% (95% CI, 47.0–60.7%; P < 0.001) in the Others and 56.8% (95% CI, 53.7–59.8%; P < 0.001) in patients without prior solid tumors (Fig. 2D). The 2-year relapse rate was comparable among the three groups (33.7% [95% CI, 19.5–48.5%], vs. 33.1% [95% CI, 27.0–39.3%; P = 0.724], vs. 30.0% [95% CI, 27.2–32.8%; P = 0.871], Fig. 2E). However, the 2-year NRM rate was significantly higher in the Chemo + RT at 36.2% (95% CI, 22.2–50.4%) compared to 18.7% (95% CI, 13.8–24.3%; P = 0.002) in the Others and 19.3% (95% CI, 17.0–21.8%; P = 0.001) in patients without prior solid tumors (Fig. 2F). There was no significant difference in OS, relapse, and NRM rates between the Others and patients without prior solid tumors. These results suggest that only a combination of Chemo + RT is associated with worse clinical outcome due to increased NRM. The common causes of NRM were infections (20.0%), acute GVHD (15.0%), bleeding (15.0%), and graft failure (15.0%) in the Chemo + RT, and infections (33.8%), idiopathic pneumonia (13.2%), chronic GVHD (10.3%), and bleeding (7.4%) in the Others. There was no significant difference between the groups ( P = 0.239, supplementary Table 5). Multivariable analyses of transplant outcomes incorporating treatment modality In the multivariable Cox regression analysis, older age, male, higher ECOG PS, high-risk diseases, and treatment with Chemo + RT for prior solid tumors were identified as significant and independent poor prognostic factors for OS (Table 4). In the multivariable competing risk analysis, male, higher ECOG PS, and high-risk diseases were independently associated with a higher risk of relapse. On the other hand, older age, male, other hematologic disorders (compared to standard-risk diseases), and treatment with Chemo + RT for prior solid tumors were independently associated with an increased risk of NRM. Discussion This is the largest multi-center retrospective study comparing transplant outcomes between patients with and without a history of solid tumors. After adjusting for baseline differences using PSM, slightly worse but not significant OS and NRM rates were observed in patients with prior solid tumors. We demonstrate that the negative impact of a combination of Chemo + RT for prior solid tumors accounts for the slightly worse clinical outcomes, while there were almost no differences between patients who received other treatment modalities for prior solid tumors and patients without prior solid tumors. These results were consistent with those obtained in a retrospective analysis from a single institution in the United States despite the different distribution of solid tumor types. 27 The study evaluated 102 patients with prior solid tumors who underwent allo-HSCT for myeloid malignancies between 2010 and 2018 and showed no significant differences were observed in OS and relapse rates. The study also reported a significantly increased risk of acute GVHD in patients with prior solid tumors, whereas we observed no significant increase in acute or chronic GVHD. This discrepancy may be due to different transplant procedures, including donor source selection and GVHD prophylaxis, and the resultant difference in the incidence of grade II-IV acute GVHD between the two cohorts (67% in the previous study vs. 34% in our study). These findings were inconsistent with those observed in the study developing the HCT-CI, in which a history of solid tumor presented one of the highest risks for NRM. 11 Considering that the initial HCT-CI study evaluated patients who underwent allo-HSCT between 1997 and 2003, this inconsistency is probably attributed to the advances in not only transplant procedures but also cancer treatment modalities, including molecularly targeted therapies and minimally invasive resection methods (such as robotic surgery and endoscopic dissection), which mitigate NRM risk. In addition, selection bias favoring allo-HSCT in patients with better expected prognoses from prior solid tumors may contribute to non-inferior OS and NRM in patients with prior solid tumors. To extend the previous findings, we focused on NRM and the impact of treatment modality, demonstrating worse prognosis due to increased NRM in patients who had received Chemo + RT for prior solid tumors. Furthermore, this association was confirmed as an independent prognostic factor in multivariable analysis. Prior exposure to chemotherapy and/or radiation therapy can have long-term effects on the hematopoietic system, potentially weakening stem cell regenerative capacity and delaying hematopoietic recovery after allo-HSCT. 28 – 30 In addition, cytotoxic agents and radiation are known to synergistically induce tissue damage through mechanisms such as reactive oxygen species accumulation and DNA double-strand breaks, 31 , 32 potentially increasing the risk of post-transplant complications in the Chemo + RT group. In this group, breast cancer accounted for over half the cases, which was significantly higher than the Others, although no significant differences in transplant outcomes were observed between patients with prior breast cancers and patients with other prior solid tumors when all treatment modalities were considered (data not shown). In breast cancer, even early-stage patients often undergo perioperative chemotherapy and/or radiation therapy, which may affect the heart and lungs. 33 Such treatment strategy for breast cancer may contribute to a higher NRM rate of the Chemo + RT group. In consistent with this, organ complications such as acute GVHD and sinusoidal obstruction syndrome (SOS) were more common causes of NRM in the Chemo + RT, although not significant due to the limited sample size. These results suggest that it is necessary to take into account not only a history of solid tumors but also its treatment modality in the assessment of comorbidities in allo-HSCT candidates, which points to a need for refining the HCT-CI. In addition, less toxic transplant procedures, including the use of RIC, may be more appropriate for patients who have a history of receiving Chemo + RT for solid tumors. The relatively large sample size and long follow-up period of this study allowed investigation of the consequences of solid tumors after allo-HSCT. Accumulating scientific and clinical evidence points to a pivotal role of anti-tumor immunity in preventing cancer initiation, progression, and recurrence. 34 , 35 Despite intense immunosuppression after allo-HSCT, our study showed that progression and/or recurrence of prior solid tumors after transplantation was rare (2.8%). Notably, no recurrence was observed in patients who had undergone surgery or endoscopic resection for early-stage esophagogastric or colorectal cancers. Therefore, it is reasonable to argue that determining the eligibility for allo-HSCT in patients with prior solid tumors at the physician's discretion in current clinical practice is appropriate. As the tumor type, stage, interval between diagnosis and transplantation, treatment modality, and response status regarding prior solid tumors varied widely, it is difficult to predict their progression and/or recurrence before allo-HSCT. Given almost all recurrences occurred within two years of transplantation, careful monitoring of solid tumors during this period is important. The limitations of this study were its retrospective nature and potential selection bias. Moreover, detailed information about molecular alterations of hematologic disorders and treatment modalities for prior solid tumors, including type and duration of chemotherapy as well as radiation dose and site, was lacking. In addition, our cohort consisted of a heterogenous population of hematologic disorders. This may obscure the effect of prior solid tumors and their treatment modality, compared to many reports focusing on a single entity, such as therapy-related AML (AML developing after exposure of chemotherapy and/or radiation therapy for prior solid tumors or hematologic malignancies). 36 , 37 However, our cohort is thought to more reliably reflect the real-world distribution of solid tumor types and their related treatment modalities in allo-HSCT recipients. In conclusion, our study demonstrated that prior exposure to Chemo + RT for prior solid tumors is an independent risk factor for worse OS and increased NRM, while other treatment modalities do not affect transplant outcomes. In addition, progression and/or recurrence of solid tumors is rare in selected allo-HSCT recipients. These findings provide valuable insights into determining the feasibility of allo-HSCT in patients with a history of solid tumors. Declarations Authorship contributions TF, MS, and KK designed the study, performed the analyses, and wrote the manuscript. HS, AI, KK, KS, ST, YO, SK, SM, ES, AJ, FO, YN, TK, TT, MS, SI, MO, SY, KH, MH, NA, SF, ST, NK, TK and KT contributed to data collection and revised the manuscript. KK and YK supervised the study. All authors discussed the results and reviewed the manuscript. Financial disclosures The authors received no specific financial support for this work. Conflict of interest statement KK received honoraria from Ono Pharmaceutical, Eisai, Astellas Pharma, Novartis, Chugai Pharmaceutical, AstraZeneca, Sumitomo Pharma, Kyowa Kirin, Janssen Pharmaceutical, Takeda Pharmaceutical, Otsuka Pharmaceutical, SymBio Pharmaceuticals, Bristol Myers Squibb, Pfizer, Nippon Shinyaku, Daiichi Sankyo, Alexion Pharmaceuticals, AbbVie, Meiji Seika Pharma, Sanofi, Sysmex, Mundipharma, Incyte Corporation, and Kyorin Pharmaceutical. KK received research support from Otsuka Pharmaceutical, Chordia Therapeutics, Chugai Pharmaceutical, Takeda Pharmaceutical, and Meiji Seika Pharma. KK received scholarship from Asahi Kasei Pharma, Eisai, Otsuka Pharmaceutical, Ono Pharmaceutical, Kyowa Kirin, Shionogi, Takeda Pharmaceutical, Sumitomo Dainippon Pharma, Chugai Pharmaceutical, Teijin Pharma, Japan Blood Products Organization, Mochida Pharmaceutical, JCR Pharmaceuticals, and Nippon Shinyaku. KK owns stock in Asahi Genomics. KK has a patent for Genetic alterations as a biomarker in T-cell lymphomas and a patent for PD-L1 abnormalities as a predictive biomarker for immune checkpoint blockade therapy. SF reports honoraria from Bristol-Myers-Squibb, Nippon Shinyaku, Otsuka Pharmaceutical Co., Ltd., Pfizer Japan Inc., Novartis Pharma KK, Janssen, Kyowa Kirin Co., Ltd., AstraZeneca, CSL Behring K.K, Meiji Seika Pharma, AbbVie Inc, Takeda Pharmaceutical Co., Ltd., Asahi Kasei Pharma Co., Ltd., Daiichi Sankyo Co., Ltd., Kissei, PharmaEssentia Japan, Genmab, Argenx Japan, Alexion Pharma, Inc., and Chugai Pharmaceutical Co., Ltd. and research funding from Shionogi Co., Ltd., Chugai Pharmaceutical Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Asahi-Kasei Pharma, and Daiichi Sankyo Co., Ltd., outside of the submitted work. Acknowledgements The authors thank all patients who participated in the study and all members of Kanto Study of Group for Cell Therapy (KSGCT). The authors also thank Toyohiro Kawano and the members of the KSGCT data center for data management. 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Additional Declarations Yes Supplementary Files Table1.xlsx Table2.xlsx Table3.xlsx Table4.xlsx Supplementary.pdf Supplemental material Cite Share Download PDF Status: Published Journal Publication published 15 Sep, 2025 Read the published version in Bone Marrow Transplantation → Version 1 posted Editorial decision: revise 16 Jun, 2025 Review # 1 received at journal 12 Jun, 2025 Review # 2 received at journal 08 Jun, 2025 Reviewer # 2 agreed at journal 26 May, 2025 Reviewer # 1 agreed at journal 18 May, 2025 Reviewers invited by journal 06 May, 2025 Submission checks completed at journal 06 May, 2025 First submitted to journal 06 May, 2025 Unknown event 06 May, 2025 Editor assigned by journal 05 May, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Kataoka","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAxklEQVRIiWNgGAWjYBACCQY2MG3Az8PAcIAByiOsBajUQLKHZC0GZ4h1mGR7W+LnDzU2xsZnDh888IGBL4+gFmmeY4clDhxLMzM725ZwcAYDWzFBLXIS6Q0SB9gO25id5zE4zMPAlthAUIv88+YfB/4dtjHu5/9AnBZpCbZjEgfbDpsZ8PYwEKdFsictzeJsX5qxxJljBgdnGBDhF4njx4xvVHyzMezvSX784UPFMcIhhgYMjiWQqoWhhnQto2AUjIJRMOwBAOpvPxnchx4lAAAAAElFTkSuQmCC","orcid":"","institution":"Keio University School of Medicine","correspondingAuthor":true,"prefix":"","firstName":"Keisuke","middleName":"","lastName":"Kataoka","suffix":""},{"id":452961481,"identity":"9d0ca4cb-5446-42e0-be97-52e5dd652f5e","order_by":1,"name":"Takayuki Fujii","email":"","orcid":"","institution":"Keio University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Takayuki","middleName":"","lastName":"Fujii","suffix":""},{"id":452961482,"identity":"22225fb9-3f74-48fa-a3da-de0f7553b6ae","order_by":2,"name":"Masatoshi 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Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yuho","middleName":"","lastName":"Najima","suffix":""},{"id":452961495,"identity":"f719c7e2-26e0-4783-a23d-c60c3ae70344","order_by":15,"name":"Takeshi Kobayashi","email":"","orcid":"","institution":"Tokyo Metropolitan Cancer and Infectious Diseases Center","correspondingAuthor":false,"prefix":"","firstName":"Takeshi","middleName":"","lastName":"Kobayashi","suffix":""},{"id":452961496,"identity":"d94c87bb-b364-42cc-865a-864fda559f2d","order_by":16,"name":"Takayoshi Tachibana","email":"","orcid":"","institution":"Kanagawa Cancer Center","correspondingAuthor":false,"prefix":"","firstName":"Takayoshi","middleName":"","lastName":"Tachibana","suffix":""},{"id":452961497,"identity":"2fd99ecd-da0d-447f-9798-8badb5b0ad8c","order_by":17,"name":"Masatsugu Tanaka","email":"","orcid":"","institution":"Kanagawa Cancer 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Medicine","correspondingAuthor":false,"prefix":"","firstName":"Shingo","middleName":"","lastName":"Yano","suffix":""},{"id":452961501,"identity":"969e76dc-2184-4bca-9c71-b2c3a809316d","order_by":21,"name":"Kaoru Hatano","email":"","orcid":"","institution":"Jichi Medical University","correspondingAuthor":false,"prefix":"","firstName":"Kaoru","middleName":"","lastName":"Hatano","suffix":""},{"id":452961502,"identity":"4e22eb92-c891-4be8-b3c6-66169b7f8417","order_by":22,"name":"Maki Hagihara","email":"","orcid":"","institution":"Yokohama City University Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Maki","middleName":"","lastName":"Hagihara","suffix":""},{"id":452961503,"identity":"d8655594-cd44-4f2c-8b78-c1ac0250ffc3","order_by":23,"name":"Nobuyuki Aotsuka","email":"","orcid":"","institution":"Japanese Red Cross Society Narita Hospital","correspondingAuthor":false,"prefix":"","firstName":"Nobuyuki","middleName":"","lastName":"Aotsuka","suffix":""},{"id":452961504,"identity":"8ab42a7e-1ede-44b7-a73b-62c2b48511aa","order_by":24,"name":"Shin Fujisawa","email":"","orcid":"","institution":"Yokohama City University Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Shin","middleName":"","lastName":"Fujisawa","suffix":""},{"id":452961505,"identity":"86b70981-e585-4874-a268-008c728f3c94","order_by":25,"name":"Satoshi Takahashi","email":"","orcid":"https://orcid.org/0000-0002-1076-2338","institution":"The Institute of Medical Science, The University of Tokyo","correspondingAuthor":false,"prefix":"","firstName":"Satoshi","middleName":"","lastName":"Takahashi","suffix":""},{"id":452961506,"identity":"f7b2a0f9-d386-49fd-bb4a-027512ea432d","order_by":26,"name":"Nobuhiko Kobayashi","email":"","orcid":"","institution":"Gunma University","correspondingAuthor":false,"prefix":"","firstName":"Nobuhiko","middleName":"","lastName":"Kobayashi","suffix":""},{"id":452961507,"identity":"e6f41b0c-aa38-4baa-8b85-bc6f4349fbcd","order_by":27,"name":"Taku Kikuchi","email":"","orcid":"https://orcid.org/0000-0002-3210-7756","institution":"Japanese Red Cross Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Taku","middleName":"","lastName":"Kikuchi","suffix":""},{"id":452961508,"identity":"932a652b-ba51-4a06-9a24-1d8417ea44cd","order_by":28,"name":"Keisuke Tanaka","email":"","orcid":"","institution":"Graduate School of Medical and Dental Sciences, Institute of Science Tokyo","correspondingAuthor":false,"prefix":"","firstName":"Keisuke","middleName":"","lastName":"Tanaka","suffix":""},{"id":452961509,"identity":"d00e3835-ea97-49e3-8292-c1ba3d1b2edc","order_by":29,"name":"Yoshinobu Kanda","email":"","orcid":"https://orcid.org/0000-0002-4866-9307","institution":"Division of Hematology, Department of Medicine, Jichi Medical University, Tochigi, Japan","correspondingAuthor":false,"prefix":"","firstName":"Yoshinobu","middleName":"","lastName":"Kanda","suffix":""}],"badges":[],"createdAt":"2025-05-05 15:55:13","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6595951/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6595951/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41409-025-02718-8","type":"published","date":"2025-09-15T04:00:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":82602836,"identity":"21d4e135-ad63-478f-9112-22eee79eb282","added_by":"auto","created_at":"2025-05-13 09:51:53","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":291599,"visible":true,"origin":"","legend":"\u003cp\u003eLegend not included with this version\u003c/p\u003e","description":"","filename":"fig1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6595951/v1/3e868e9f218b5ac26f7bc38c.jpg"},{"id":82605056,"identity":"15f4651c-bd1e-44ea-b26d-8a770bfee67e","added_by":"auto","created_at":"2025-05-13 09:59:52","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":483814,"visible":true,"origin":"","legend":"\u003cp\u003eLegend not included with this version\u003c/p\u003e","description":"","filename":"fig2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6595951/v1/73a7ae4fc145926f658ca84d.jpg"},{"id":91817761,"identity":"7dab89f8-9d7d-4c42-87c1-d6a56d4a1840","added_by":"auto","created_at":"2025-09-22 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09:51:52","extension":"xlsx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":12195,"visible":true,"origin":"","legend":"","description":"","filename":"Table2.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-6595951/v1/b44dca64ae040f901cf0985d.xlsx"},{"id":82602835,"identity":"fdbc230d-2124-4d2a-b63b-d0111cdd1711","added_by":"auto","created_at":"2025-05-13 09:51:53","extension":"xlsx","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":12617,"visible":true,"origin":"","legend":"","description":"","filename":"Table3.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-6595951/v1/3071efa9a16647c7d6210de1.xlsx"},{"id":82602837,"identity":"8f50df1e-9f21-4fff-822d-daa8b4a57cd4","added_by":"auto","created_at":"2025-05-13 09:51:54","extension":"xlsx","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":18617,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cbr\u003e\u003c/p\u003e","description":"","filename":"Table4.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-6595951/v1/72b8f85b82e435eb8f101e4d.xlsx"},{"id":82605054,"identity":"c365c866-0e6d-43fb-b1db-641a2dc9fff1","added_by":"auto","created_at":"2025-05-13 09:59:52","extension":"pdf","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":856828,"visible":true,"origin":"","legend":"\u003cp\u003eSupplemental material\u003c/p\u003e","description":"","filename":"Supplementary.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6595951/v1/d9de242ec5db4068fc878f32.pdf"}],"financialInterests":"\u003cb\u003eYes\u003c/b\u003e","formattedTitle":"\u003cp\u003e\u003cstrong\u003eImpact of prior solid tumors and their treatment modality on outcomes after allogeneic hematopoietic stem cell transplantation: A KSGCT multi-center retrospective study\u003c/strong\u003e\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAllogeneic hematopoietic stem cell transplantation (allo-HSCT) is a well-established and potentially curative treatment for various hematologic disorders, including hematologic malignancies and bone marrow failure syndromes.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e Although advances in transplantation techniques have improved the safety and efficacy of allo-HSCT, it remains associated with significant morbidity and mortality, including infections, conditioning-related toxicities, and graft-versus-host disease (GVHD), even in patients who do not experience relapse.\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e,\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e Therefore, eligibility for allo-HSCT should be carefully assessed based on disease status, age, PS, comorbidities, and donor availability. \u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eThe incidence of cancers is increasing worldwide, and it is currently estimated that approximately one in five individuals will develop cancer during their lifetime.\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e With the advances in cancer treatment, the number of cancer survivors is also increasing. Furthermore, chemotherapy and/or radiation therapy for solid tumors can increase the risk of developing hematologic malignancies, particularly myeloid neoplasms.\u003csup\u003e\u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e These facts result in an increasing number of patients with a history of solid tumors undergoing allo-HSCT.\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e,\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e Such patients are thought to have a higher risk of non-relapse mortality (NRM), as represented by the hematopoietic cell transplantation-specific comorbidity index (HCT-CI), which is the most widely used scoring system for risk assessment of patients undergoing allo-HSCT. \u003csup\u003e\u003cspan additionalcitationids=\"CR12\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e In this score, a history of solid tumor (excluding non-melanoma skin cancer) is given the highest weight of 3 points, along with heart valve disease, severe pulmonary dysfunction, and moderate to severe hepatic dysfunction, based on hazard ratios (HR) for 2-year NRM.\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003ePatients with solid tumors undergo various treatment modalities, including surgery, endoscopic resection, chemotherapy, radiation therapy, and molecularly targeted agents. In addition to progression and/or recurrence of solid tumors, prior treatment for solid tumors may contribute to the increased risk of NRM through inducing tissue damage. However, the effect of different treatment modalities on NRM remains unknown. In addition, the incidences of solid tumor types vary by race and country,\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e and these differences in tumor distribution and treatment approaches may influence the effect of prior solid tumors on transplant outcomes.\u003c/p\u003e \u003cp\u003eIt is well known that factors such as conditioning regimens, GVHD, its prophylaxis and treatment, and delayed hematopoietic recovery can cause immunosuppression in allo-HSCT recipients.\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e,\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e,\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e This immunosuppression raises concerns about an increased risk of the progression and/or recurrence of solid tumors, but the consequences of prior solid tumors after allo-HSCT have not been well investigated. Overall, determining the eligibility for allo-HSCT in patients with hematologic disorders who have a history of solid tumors is challenging in the real world.\u003c/p\u003e \u003cp\u003eTo address these issues, this study evaluated the impact of a history of solid tumors and their treatment modalities on transplant outcomes in allo-HSCT recipients and clarified the consequences of prior solid tumors after transplantation using a large-scale Japanese database.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design and data source\u003c/h2\u003e \u003cp\u003eThis study is a retrospective cohort analysis of adult patients aged\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026ge;\u003c/span\u003e\u0026thinsp;16 years undergoing first allo-HSCT between 2010 and 2022 at 20 institutions participating in the Kanto Study Group for Cell Therapy (KSGCT). Data were collected from the KSGCT database. Detailed information on prior solid tumors was collected through a secondary survey, including tumor type, stage, date of diagnosis, treatment modalities, response (complete remission [CR], partial remission [PR], stable disease [SD], and progressive disease) at the time of transplantation, and the presence and timing of progression or recurrence. Non-melanoma skin cancers were excluded from prior solid tumors according to the HCT-CI definition.\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e Patients who developed therapy-related myeloid neoplasms (t-MN) following treatment for a prior hematologic malignancy were excluded. This study was conducted in accordance with the Declaration of Helsinki and was approved by the ethics committee of Keio University School of Medicine (Tokyo, Japan) (approval number 20231134).\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eDefinition\u003c/h3\u003e\n\u003cp\u003eAcute and chronic GVHD were diagnosed and graded using established criteria.\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e,\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e Conditioning regimens were classified into myeloablative conditioning (MAC) or reduced-intensity conditioning (RIC) based on the criteria of the Center for International Blood and Marrow Transplant Research (CIBMTR).\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e,\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e t-MN was defined as a myeloid neoplasm that developed following chemotherapy and/or radiation therapy for a prior solid tumor.\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e,\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e Standard-risk diseases included acute myeloid leukemia (AML) in first or second CR, acute lymphoblastic leukemia (ALL) in first CR, chronic myeloid leukemia (CML) in chronic/accelerated phase, low-risk myelodysplastic syndrome (MDS), myeloproliferative neoplasms (MPN), lymphomas with CR/PR, and plasma cell neoplasms in CR/very good PR/PR. The remaining hematologic disorders, mainly bone marrow failure syndromes, were classified as others. Treatment modalities for prior solid tumors were classified into radical resection (surgery or endoscopic resection), chemotherapy, radiation therapy, both chemotherapy and radiation therapy (Chemo\u0026thinsp;+\u0026thinsp;RT), and others (molecularly targeted and hormone therapy). Patients who received chemotherapy and/or radiation therapy were classified accordingly, regardless of whether they also underwent surgery or other treatments. Those who received Chemo\u0026thinsp;+\u0026thinsp;RT, either concurrently or sequentially, were classified into the Chemo\u0026thinsp;+\u0026thinsp;RT group.\u003c/p\u003e\n\u003ch3\u003ePropensity score matching\u003c/h3\u003e\n\u003cp\u003ePropensity score matching (PSM) was performed to balance patients with and without prior solid tumors.\u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e,\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e Propensity scores were estimated using logistic regression models. A 1:4 nearest neighbor matching with a fixed caliper width of 0.2 was applied. A standardized mean difference\u0026thinsp;\u0026lt;\u0026thinsp;0.10 was considered acceptable.\u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eBaseline characteristics were compared using Fisher\u0026rsquo;s exact and Mann-Whitney U tests. Overall survival (OS) was estimated by the Kaplan-Meier method, and compared using the log-rank test. Multivariable OS analysis was conducted using the Cox proportional hazards regression models. The cumulative incidence of relapse, NRM, and acute and chronic GVHD was estimated considering competing risks. Univariable and multivariable analyses for relapse and NRM were conducted using the Fine and Gray model. All tests were two-sided with P values\u0026thinsp;\u0026lt;\u0026thinsp;0.05 considered significant. Analyses were conducted using EZR,\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e a graphical user interface for R (The R Foundation for Statistical Computing, Vienna, Austria).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003ePatient and transplant characteristics\u003c/h2\u003e \u003cp\u003eA total of 5,850 patients were initially identified. Among them, 63 patients who developed t-MN following treatment for prior hematologic malignancies were excluded. Of the remaining 5,787 patients, 303 (5.2%) had a history of solid tumors, while 5,484 (94.8%) had no such history (Fig.\u0026nbsp;1). Patients and transplant characteristics are summarized in Table\u0026nbsp;1. Patients with a history of solid tumors were older and had a higher proportion of females. They also had a significantly higher prevalence of myeloid malignancies, such as AML and MDS or MPN, with 134 patients (44.2%) being classified as t-MN. The use of RIC was more common in this group. In addition, a higher proportion of these patients underwent allo-HSCT between 2018 and 2022.\u003c/p\u003e \u003cp\u003eThe characteristics of prior solid tumors in our cohort are detailed in Table\u0026nbsp;2. Among solid tumor types, breast cancer (24.4%) was the most common. Among patients whose tumor stage information was available, stages 0\u0026ndash;I were the most frequent (24.8%). At the time of allo-HSCT, most patients were in CR (89.1%). Regarding the treatment modalities for solid tumors, radical resection was the most common (37.6%), followed by chemotherapy (25.1%). The median time from diagnosis of prior solid tumors to allo-HSCT was 6.0 years.\u003c/p\u003e \u003cp\u003eAfter performing PSM, 277 patients with a history of prior solid tumors were matched with 1,108 patients without such a history (Fig.\u0026nbsp;1). The two groups were well balanced, with no significant differences in baseline characteristics (supplementary Table\u0026nbsp;1). The characteristics of patients with a history of prior solid tumors after PSM were similar to those before PSM (supplementary Table\u0026nbsp;2).\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eTransplant outcomes\u003c/h3\u003e\n\u003cp\u003eIn 277 patients with prior solid tumors and 1,108 patients without prior solid tumors after PSM, the median follow-up period for survivors was 62 months (range, 0.3\u0026ndash;173 months). The 2-year OS rate of patients with prior solid tumors was slightly worse but not significantly different compared to those without prior solid tumors (51.2% [95% CI, 44.8\u0026ndash;57.2%] vs. 56.8% [95% CI, 53.7\u0026ndash;59.8%], \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.116, Fig.\u0026nbsp;2A). Similarly, the 2-year relapse rate was not significantly different between the two groups (32.9% [95% CI, 27.3\u0026ndash;38.6%] vs. 28.8% [95% CI, 26.1\u0026ndash;31.6%], \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.191, Fig.\u0026nbsp;2B). The 2-year NRM rate was also comparable (21.5% [95% CI, 16.7\u0026ndash;26.7%] vs. 20.2% [95% CI, 17.8\u0026ndash;22.7%], \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.293, Fig.\u0026nbsp;2C).\u003c/p\u003e \u003cp\u003eIn addition, no significant differences were observed in acute and chronic GVHD incidences between the two groups. The 3-month cumulative incidence of grade II-IV acute GVHD was 36.5% (95% CI, 30.8\u0026ndash;42.1%) in patients with prior solid tumors and 32.4% (95% CI, 29.6\u0026ndash;35.1%) in those without (supplementary Fig.\u0026nbsp;1A). Similarly, the 2-year cumulative incidence of chronic GVHD was 29.8% (95% CI, 24.4\u0026ndash;35.5%) and 31.3% (95% CI, 28.5\u0026ndash;34.2%) in the respective groups (supplementary Fig.\u0026nbsp;1B).\u003c/p\u003e\n\u003ch3\u003eProgression and/or recurrence of prior solid tumors\u003c/h3\u003e\n\u003cp\u003eAmong 290 patients whose follow-up data for prior solid tumors were available, only eight (2.8%) patients experienced progression and/or recurrence of their prior solid tumors after allo-HSCT (Table\u0026nbsp;3). These solid tumors included head and neck, lung, esophagogastric, gynecologic cancer, and urologic cancer. Among them, four patients had stage I diseases, and four patients received systemic chemotherapy with or without radiation therapy, achieving CR at transplantation. The median time from solid tumor diagnosis to allo-HSCT was 2.9 years. Of six patients with available data, five experienced tumor progression and/or recurrence within two years after transplantation. There were three deaths, including two of progression and/or recurrence of solid tumors and one of relapse of hematologic disorder.\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eImpact of treatment modality for prior solid tumors on transplant outcomes\u003c/h2\u003e \u003cp\u003eTo evaluate the impact of treatment modality for prior solid tumors on transplant outcomes, we compared OS, relapse, and NRM rates among patients who received radical resection, chemotherapy, radiation therapy, Chemo\u0026thinsp;+\u0026thinsp;RT, and other treatment modalities for prior solid tumors (n\u0026thinsp;=\u0026thinsp;272) and patients without prior solid tumors (n\u0026thinsp;=\u0026thinsp;1,108). As patients who received radical resection, chemotherapy, radiation therapy, and other treatments showed similar OS, relapse, and NRM rates (Table\u0026nbsp;4), they were grouped as Others (n\u0026thinsp;=\u0026thinsp;227) and compared with patients who received Chemo\u0026thinsp;+\u0026thinsp;RT (n\u0026thinsp;=\u0026thinsp;45). A comparison of patient characteristics revealed a higher proportion of female patients in the Chemo\u0026thinsp;+\u0026thinsp;RT than in the Others (75.6% vs. 51.5%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.005, supplementary Table\u0026nbsp;3). In addition, the Chemo\u0026thinsp;+\u0026thinsp;RT group had a significantly greater proportion of breast cancer (57.7% vs. 18.5%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and contained more tumors with advanced stages (stage II or higher) (40.0% vs. 16.3%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.002, supplementary Table\u0026nbsp;4).\u003c/p\u003e \u003cp\u003eThe 2-year OS rate was significantly worse in the Chemo\u0026thinsp;+\u0026thinsp;RT at 35.3% (95% CI, 20.9\u0026ndash;50.1%) compared to 54.1% (95% CI, 47.0\u0026ndash;60.7%; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) in the Others and 56.8% (95% CI, 53.7\u0026ndash;59.8%; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) in patients without prior solid tumors (Fig.\u0026nbsp;2D). The 2-year relapse rate was comparable among the three groups (33.7% [95% CI, 19.5\u0026ndash;48.5%], vs. 33.1% [95% CI, 27.0\u0026ndash;39.3%; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.724], vs. 30.0% [95% CI, 27.2\u0026ndash;32.8%; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.871], Fig.\u0026nbsp;2E). However, the 2-year NRM rate was significantly higher in the Chemo\u0026thinsp;+\u0026thinsp;RT at 36.2% (95% CI, 22.2\u0026ndash;50.4%) compared to 18.7% (95% CI, 13.8\u0026ndash;24.3%; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.002) in the Others and 19.3% (95% CI, 17.0\u0026ndash;21.8%; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001) in patients without prior solid tumors (Fig.\u0026nbsp;2F). There was no significant difference in OS, relapse, and NRM rates between the Others and patients without prior solid tumors. These results suggest that only a combination of Chemo\u0026thinsp;+\u0026thinsp;RT is associated with worse clinical outcome due to increased NRM.\u003c/p\u003e \u003cp\u003eThe common causes of NRM were infections (20.0%), acute GVHD (15.0%), bleeding (15.0%), and graft failure (15.0%) in the Chemo\u0026thinsp;+\u0026thinsp;RT, and infections (33.8%), idiopathic pneumonia (13.2%), chronic GVHD (10.3%), and bleeding (7.4%) in the Others. There was no significant difference between the groups (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.239, supplementary Table\u0026nbsp;5).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eMultivariable analyses of transplant outcomes incorporating treatment modality\u003c/h2\u003e \u003cp\u003eIn the multivariable Cox regression analysis, older age, male, higher ECOG PS, high-risk diseases, and treatment with Chemo\u0026thinsp;+\u0026thinsp;RT for prior solid tumors were identified as significant and independent poor prognostic factors for OS (Table\u0026nbsp;4).\u003c/p\u003e \u003cp\u003eIn the multivariable competing risk analysis, male, higher ECOG PS, and high-risk diseases were independently associated with a higher risk of relapse. On the other hand, older age, male, other hematologic disorders (compared to standard-risk diseases), and treatment with Chemo\u0026thinsp;+\u0026thinsp;RT for prior solid tumors were independently associated with an increased risk of NRM.\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis is the largest multi-center retrospective study comparing transplant outcomes between patients with and without a history of solid tumors. After adjusting for baseline differences using PSM, slightly worse but not significant OS and NRM rates were observed in patients with prior solid tumors. We demonstrate that the negative impact of a combination of Chemo\u0026thinsp;+\u0026thinsp;RT for prior solid tumors accounts for the slightly worse clinical outcomes, while there were almost no differences between patients who received other treatment modalities for prior solid tumors and patients without prior solid tumors. These results were consistent with those obtained in a retrospective analysis from a single institution in the United States despite the different distribution of solid tumor types. \u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e The study evaluated 102 patients with prior solid tumors who underwent allo-HSCT for myeloid malignancies between 2010 and 2018 and showed no significant differences were observed in OS and relapse rates. The study also reported a significantly increased risk of acute GVHD in patients with prior solid tumors, whereas we observed no significant increase in acute or chronic GVHD. This discrepancy may be due to different transplant procedures, including donor source selection and GVHD prophylaxis, and the resultant difference in the incidence of grade II-IV acute GVHD between the two cohorts (67% in the previous study vs. 34% in our study).\u003c/p\u003e \u003cp\u003eThese findings were inconsistent with those observed in the study developing the HCT-CI, in which a history of solid tumor presented one of the highest risks for NRM.\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e Considering that the initial HCT-CI study evaluated patients who underwent allo-HSCT between 1997 and 2003, this inconsistency is probably attributed to the advances in not only transplant procedures but also cancer treatment modalities, including molecularly targeted therapies and minimally invasive resection methods (such as robotic surgery and endoscopic dissection), which mitigate NRM risk. In addition, selection bias favoring allo-HSCT in patients with better expected prognoses from prior solid tumors may contribute to non-inferior OS and NRM in patients with prior solid tumors.\u003c/p\u003e \u003cp\u003eTo extend the previous findings, we focused on NRM and the impact of treatment modality, demonstrating worse prognosis due to increased NRM in patients who had received Chemo\u0026thinsp;+\u0026thinsp;RT for prior solid tumors. Furthermore, this association was confirmed as an independent prognostic factor in multivariable analysis. Prior exposure to chemotherapy and/or radiation therapy can have long-term effects on the hematopoietic system, potentially weakening stem cell regenerative capacity and delaying hematopoietic recovery after allo-HSCT.\u003csup\u003e\u003cspan additionalcitationids=\"CR29\" citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e In addition, cytotoxic agents and radiation are known to synergistically induce tissue damage through mechanisms such as reactive oxygen species accumulation and DNA double-strand breaks,\u003csup\u003e\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e,\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u003c/sup\u003e potentially increasing the risk of post-transplant complications in the Chemo\u0026thinsp;+\u0026thinsp;RT group. In this group, breast cancer accounted for over half the cases, which was significantly higher than the Others, although no significant differences in transplant outcomes were observed between patients with prior breast cancers and patients with other prior solid tumors when all treatment modalities were considered (data not shown). In breast cancer, even early-stage patients often undergo perioperative chemotherapy and/or radiation therapy, which may affect the heart and lungs. \u003csup\u003e\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u003c/sup\u003e Such treatment strategy for breast cancer may contribute to a higher NRM rate of the Chemo\u0026thinsp;+\u0026thinsp;RT group. In consistent with this, organ complications such as acute GVHD and sinusoidal obstruction syndrome (SOS) were more common causes of NRM in the Chemo\u0026thinsp;+\u0026thinsp;RT, although not significant due to the limited sample size. These results suggest that it is necessary to take into account not only a history of solid tumors but also its treatment modality in the assessment of comorbidities in allo-HSCT candidates, which points to a need for refining the HCT-CI. In addition, less toxic transplant procedures, including the use of RIC, may be more appropriate for patients who have a history of receiving Chemo\u0026thinsp;+\u0026thinsp;RT for solid tumors.\u003c/p\u003e \u003cp\u003eThe relatively large sample size and long follow-up period of this study allowed investigation of the consequences of solid tumors after allo-HSCT. Accumulating scientific and clinical evidence points to a pivotal role of anti-tumor immunity in preventing cancer initiation, progression, and recurrence.\u003csup\u003e\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e,\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u003c/sup\u003e Despite intense immunosuppression after allo-HSCT, our study showed that progression and/or recurrence of prior solid tumors after transplantation was rare (2.8%). Notably, no recurrence was observed in patients who had undergone surgery or endoscopic resection for early-stage esophagogastric or colorectal cancers. Therefore, it is reasonable to argue that determining the eligibility for allo-HSCT in patients with prior solid tumors at the physician's discretion in current clinical practice is appropriate. As the tumor type, stage, interval between diagnosis and transplantation, treatment modality, and response status regarding prior solid tumors varied widely, it is difficult to predict their progression and/or recurrence before allo-HSCT. Given almost all recurrences occurred within two years of transplantation, careful monitoring of solid tumors during this period is important.\u003c/p\u003e \u003cp\u003eThe limitations of this study were its retrospective nature and potential selection bias. Moreover, detailed information about molecular alterations of hematologic disorders and treatment modalities for prior solid tumors, including type and duration of chemotherapy as well as radiation dose and site, was lacking. In addition, our cohort consisted of a heterogenous population of hematologic disorders. This may obscure the effect of prior solid tumors and their treatment modality, compared to many reports focusing on a single entity, such as therapy-related AML (AML developing after exposure of chemotherapy and/or radiation therapy for prior solid tumors or hematologic malignancies).\u003csup\u003e\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e,\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e\u003c/sup\u003e However, our cohort is thought to more reliably reflect the real-world distribution of solid tumor types and their related treatment modalities in allo-HSCT recipients.\u003c/p\u003e \u003cp\u003eIn conclusion, our study demonstrated that prior exposure to Chemo\u0026thinsp;+\u0026thinsp;RT for prior solid tumors is an independent risk factor for worse OS and increased NRM, while other treatment modalities do not affect transplant outcomes. In addition, progression and/or recurrence of solid tumors is rare in selected allo-HSCT recipients. These findings provide valuable insights into determining the feasibility of allo-HSCT in patients with a history of solid tumors.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eAuthorship contributions\u003c/h2\u003e \u003cp\u003eTF, MS, and KK designed the study, performed the analyses, and wrote the manuscript. HS, AI, KK, KS, ST, YO, SK, SM, ES, AJ, FO, YN, TK, TT, MS, SI, MO, SY, KH, MH, NA, SF, ST, NK, TK and KT contributed to data collection and revised the manuscript. KK and YK supervised the study. All authors discussed the results and reviewed the manuscript.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eFinancial disclosures\u003c/strong\u003e \u003cp\u003eThe authors received no specific financial support for this work.\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eConflict of interest statement\u003c/h2\u003e \u003cp\u003eKK received honoraria from Ono Pharmaceutical, Eisai, Astellas Pharma, Novartis, Chugai Pharmaceutical, AstraZeneca, Sumitomo Pharma, Kyowa Kirin, Janssen Pharmaceutical, Takeda Pharmaceutical, Otsuka Pharmaceutical, SymBio Pharmaceuticals, Bristol Myers Squibb, Pfizer, Nippon Shinyaku, Daiichi Sankyo, Alexion Pharmaceuticals, AbbVie, Meiji Seika Pharma, Sanofi, Sysmex, Mundipharma, Incyte Corporation, and Kyorin Pharmaceutical. KK received research support from Otsuka Pharmaceutical, Chordia Therapeutics, Chugai Pharmaceutical, Takeda Pharmaceutical, and Meiji Seika Pharma. KK received scholarship from Asahi Kasei Pharma, Eisai, Otsuka Pharmaceutical, Ono Pharmaceutical, Kyowa Kirin, Shionogi, Takeda Pharmaceutical, Sumitomo Dainippon Pharma, Chugai Pharmaceutical, Teijin Pharma, Japan Blood Products Organization, Mochida Pharmaceutical, JCR Pharmaceuticals, and Nippon Shinyaku. KK owns stock in Asahi Genomics. KK has a patent for Genetic alterations as a biomarker in T-cell lymphomas and a patent for PD-L1 abnormalities as a predictive biomarker for immune checkpoint blockade therapy. SF reports honoraria from Bristol-Myers-Squibb, Nippon Shinyaku, Otsuka Pharmaceutical Co., Ltd., Pfizer Japan Inc., Novartis Pharma KK, Janssen, Kyowa Kirin Co., Ltd., AstraZeneca, CSL Behring K.K, Meiji Seika Pharma, AbbVie Inc, Takeda Pharmaceutical Co., Ltd., Asahi Kasei Pharma Co., Ltd., Daiichi Sankyo Co., Ltd., Kissei, PharmaEssentia Japan, Genmab, Argenx Japan, Alexion Pharma, Inc., and Chugai Pharmaceutical Co., Ltd. and research funding from Shionogi Co., Ltd., Chugai Pharmaceutical Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Asahi-Kasei Pharma, and Daiichi Sankyo Co., Ltd., outside of the submitted work.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eAcknowledgements\u003c/h2\u003e \u003cp\u003e The authors thank all patients who participated in the study and all members of Kanto Study of Group for Cell Therapy (KSGCT). The authors also thank Toyohiro Kawano and the members of the KSGCT data center for data management.\u003c/p\u003e\u003ch2\u003eData availability statement\u003c/h2\u003e \u003cp\u003eThe data of this study are not publicly available due to ethical restrictions that it exceeds the scope of the recipient/donor\u0026rsquo;s consent for research use in the registry.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eMajhail NS, Farnia SH, Carpenter PA, et al. Indications for Autologous and Allogeneic Hematopoietic Cell Transplantation: Guidelines from the American Society for Blood and Marrow Transplantation. Biology of Blood and Marrow Transplantation. 2015;21(11):1863\u0026ndash;1869.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKanate AS, Majhail NS, Savani BN, et al. Indications for Hematopoietic Cell Transplantation and Immune Effector Cell Therapy: Guidelines from the American Society for Transplantation and Cellular Therapy. Biology of Blood and Marrow Transplantation. 2020;26(7):1247\u0026ndash;1256.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTabbara IA, Zimmerman K, Morgan; Connie, Nahleh Z. Allogeneic Hematopoietic Stem Cell Transplantation: Complications and Results. Arch Intern Med. 2002;162(14):1558\u0026ndash;1566.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMcDonald GB, Sandmaier BM, Mielcarek M, et al. Survival, nonrelapse mortality, and relapse-related mortality after allogeneic hematopoietic cell transplantation: Comparing 2003\u0026ndash;2007 versus 2013\u0026ndash;2017 cohorts. Ann Intern Med. 2020;172(4):229\u0026ndash;239.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74(3):229\u0026ndash;263.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGodley LA, Larson RA. Therapy-Related Myeloid Leukemia. Seminars in Oncology. 2008;35(4):418\u0026ndash;429.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMcNerney ME, Godley LA, le Beau MM. Therapy-related myeloid neoplasms: When genetics and environment collide. Nature Reviews Cancer. 2017;17(9):513\u0026ndash;527.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMorton LM, Dores GM, Schonfeld SJ, et al. Association of Chemotherapy for Solid Tumors with Development of Therapy-Related Myelodysplastic Syndrome or Acute Myeloid Leukemia in the Modern Era. JAMA Oncol. 2019;5(3):318\u0026ndash;325.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAllemani C, Matsuda T, Di Carlo V, et al. 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Differential prognostic impact of pretransplant comorbidity on transplant outcomes by disease status and time from transplant: A single Japanese transplant centre study. Bone Marrow Transplantation. 2010;45(3):513\u0026ndash;520.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShouval R, Fein JA. The sum of the parts: what we can and cannot learn from comorbidity scores in allogeneic transplantation. Hematology Am Soc Hematol Educ Program. 2023;2023(1):715\u0026ndash;722.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKatanoda K, Hori M, Saito E, et al. Updated trends in cancer in japan: Incidence in 1985\u0026ndash;2015 and mortality in 1958\u0026ndash;2018\u0026mdash;a sign of decrease in cancer incidence. J Epidemiol. 2021;31(7):426\u0026ndash;450.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWelniak LA, Blazar BR, Murphy WJ. Immunobiology of allogeneic hematopoietic stem cell transplantation. Annual Review of Immunology. 2007;25:139\u0026ndash;170.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJenq RR, van den Brink MRM. Allogeneic haematopoietic stem cell transplantation: Individualized stem cell and immune therapy of cancer. Nature Reviews Cancer. 2010;10(3):213\u0026ndash;221.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePrzepiorka D, Weisdorf D, Martin P, et al. 1994 Consensus Conference on Acute GVHD Grading. \u003cem\u003eBone Marrow Transplant\u003c/em\u003e. 1995;15(6):825\u0026ndash;828.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\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. 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Am J Clin Pathol. 2007;127(2):197\u0026ndash;205.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMorton LM, Dores GM, Tucker MA, et al. Evolving risk of therapy-related acute myeloid leukemia following cancer chemotherapy among adults in the United States, 1975\u0026ndash;2008. Blood. 2013;121(15):2996\u0026ndash;3004.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eD\u0026rsquo;Agostino RB. Propensity score methods for bias reduction in the comparison of a treatment to a non-randomized control group. Stat Med. 1998;17(19):2265\u0026ndash;2281.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen JW, Maldonado DR, Kowalski BL, et al. Best Practice Guidelines for Propensity Score Methods in Medical Research: Consideration on Theory, Implementation, and Reporting. A Review. Arthroscopy. 2022;38(2):632\u0026ndash;642.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAustin PC. 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Hematopoietic stem cell injury induced by ionizing radiation. Antioxidants and Redox Signal. 2014;20(9):1447\u0026ndash;1462.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMendelson A, Frenette PS. Hematopoietic stem cell niche maintenance during homeostasis and regeneration. Nature Medicine. 2014;20(8):833\u0026ndash;846.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSrinivas US, Tan BWQ, Vellayappan BA, Jeyasekharan AD. ROS and the DNA damage response in cancer. Redox Biology. 2019;25.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGroelly FJ, Fawkes M, Dagg RA, Blackford AN, Tarsounas M. Targeting DNA damage response pathways in cancer. Nature Reviews Cancer. 2023;23(2):78\u0026ndash;94.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGradishar WJ, Moran MS, Abraham J, et al. Breast Cancer, Version 3.2024, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2024;22(15); 331\u0026ndash;357.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGonzalez H, Hagerling C, Werb Z. Roles of the immune system in cancer: from tumor initiation to metastatic progression. Genes Dev. 2018;32(19\u0026ndash;20):1267\u0026ndash;1284.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMellman I, Chen DS, Powles T, Turley SJ. The cancer-immunity cycle: Indication, genotype, and immunotype. Immunity. 2023;56(10):2188\u0026ndash;2205.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKayser S, D\u0026ouml; Hner K, Rgen Krauter J, et al. The impact of therapy-related acute myeloid leukemia (AML) on outcome in 2853 adult patients with newly diagnosed AML. Blood. 2011;(117):2137\u0026ndash;45.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMadanat YF, Gerds AT. Can allogeneic hematopoietic cell transplant cure therapy-related acute leukemia? Best Pract Res Clin Haematol. 2019;32(1):104\u0026ndash;113.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables 1 to 4 are available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"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-6595951/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6595951/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eDespite the increasing number of cancer survivors, the impact of prior solid tumors and their treatment modality on outcomes after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains unclear. This multi-center retrospective study compared transplant outcomes in allo-HSCT recipients with and without a history of solid tumors. Of 5,850 adult patients who underwent first allo-HSCT, 303 (5.2%) had a prior solid tumor. After propensity score matching, overall survival (OS) and cumulative incidences of relapse, non-relapse mortality (NRM), and acute and chronic graft-versus-host diseases were almost comparable between the two groups. Progression or recurrence of solid tumors after allo-HSCT occurred in only eight cases (2.8%). Importantly, patients who received both chemotherapy and radiation therapy (Chemo\u0026thinsp;+\u0026thinsp;RT) for prior solid tumors had significantly worse OS (35.3% vs. 54.1% [\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001] vs. 56.8% [\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001] at 2 years) and higher NRM (36.2% vs. 18.7% [\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.002] vs. 19.3% [\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001] at 2 years) compared to patients who received other treatment modalities for prior solid tumors or patients without prior solid tumors. These findings highlight the feasibility of allo-HSCT in selected patients with prior solid tumors, while demonstrating the negative impact of Chemo\u0026thinsp;+\u0026thinsp;RT on outcomes after allo-HSCT.\u003c/p\u003e","manuscriptTitle":"Impact of prior solid tumors and their treatment modality on outcomes after allogeneic hematopoietic stem cell transplantation: A KSGCT multi-center retrospective study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-13 09:51:47","doi":"10.21203/rs.3.rs-6595951/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"revise","date":"2025-06-16T13:54:21+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"This content is not available.","date":"2025-06-12T18:48:29+00:00","index":1,"fulltext":"This content is not available."},{"type":"editorInvitedReview","content":"This content is not available.","date":"2025-06-08T21:46:55+00:00","index":2,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2025-05-26T10:39:01+00:00","index":2,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2025-05-19T02:44:24+00:00","index":1,"fulltext":"This content is not available."},{"type":"reviewersInvited","content":"","date":"2025-05-07T02:49:36+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-05-06T15:37:46+00:00","index":"","fulltext":""},{"type":"submitted","content":"Bone Marrow Transplantation","date":"2025-05-06T13:04:54+00:00","index":"","fulltext":""},{"type":"checksFailed","content":"","date":"2025-05-06T12:28:09+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-05-05T15:50:29+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":"bb6803b9-3254-4bdd-915e-c6508d28e9e6","owner":[],"postedDate":"May 13th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":48382961,"name":"Biological sciences/Cancer/Haematological cancer"},{"id":48382962,"name":"Biological sciences/Stem cells/Haematopoietic stem cells"}],"tags":[],"updatedAt":"2025-09-22T06:52:39+00:00","versionOfRecord":{"articleIdentity":"rs-6595951","link":"https://doi.org/10.1038/s41409-025-02718-8","journal":{"identity":"bone-marrow-transplantation","isVorOnly":false,"title":"Bone Marrow Transplantation"},"publishedOn":"2025-09-15 04:00:00","publishedOnDateReadable":"September 15th, 2025"},"versionCreatedAt":"2025-05-13 09:51:47","video":"","vorDoi":"10.1038/s41409-025-02718-8","vorDoiUrl":"https://doi.org/10.1038/s41409-025-02718-8","workflowStages":[]},"version":"v1","identity":"rs-6595951","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6595951","identity":"rs-6595951","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}