GVHD prophylaxis after cord blood transplantation in patients with high-risk AML: a nationwide Japanese cohort study.

Introduction

High-risk acute myeloid leukemia (AML), including therapy-related AML (t-AML), remains a formidable clinical challenge requiring allogeneic hematopoietic cell transplantation (HCT) for curative therapy. 1 Cord blood transplantation (CBT) has emerged as a vital option for patients lacking suitable matched donors, and offers rapid donor availability, tolerance for HLA disparity, and pronounced graft-versus-leukemia effects. 2 , 3 , 4 , 5 A critical determinant of successful CBT is the selection of optimal graft-versus-host disease (GVHD) prophylaxis to balance immune reconstitution with robust disease control. 6 Traditional regimens incorporating methotrexate (MTX) are effective for preventing GVHD but may delay hematopoietic recovery and increase mucosal toxicity. 7 In contrast, mycophenolate mofetil (MMF) has recently gained attention for its potential to accelerate engraftment and reduce the incidence of severe GVHD, as supported by evidence from haploidentical transplantation protocols. 8 Despite widespread practice variation, direct comparative data between cyclosporine or tacrolimus plus MMF (CSP/TAC + MMF) and CSP/TAC + MTX in recipients with high-risk AML who undergo CBT remain limited.

CPX-351 is a next-generation formulation of standard AML chemotherapy and is designed for patients with high-risk subtypes. 9 Traditional AML chemotherapy often combines daunorubicin and cytarabine as separate drugs, which may not be delivered to leukemia cells in the optimal ratio. The use of CPX-351 addresses this issue by packaging both drugs together in tiny fat-based particles called liposomes, at a fixed 5:1 molar ratio, which is the most effective for killing leukemia cells. Liposomal delivery enables the drugs to remain in the circulation for a longer period and accumulate in the bone marrow, thereby directly targeting the site of disease. Clinical trials have shown that CPX-351 improves remission and overall survival (OS) rates compared with standard chemotherapy in t-AML and AML with myelodysplasia-related changes (AML-MRC), leading to its approval as the first chemotherapy specifically indicated for these patient groups. 9

Using a large, multicenter, national registry cohort, this study aimed to evaluate the clinical effect of GVHD prophylaxis strategies on various variables, including OS, the incidence and severity of GVHD, and relapse rates, in patients with high-risk AML undergoing CBT in Japan. The stratification of patients is a key element in this study. We compared the subgroups of t-AML vs non-t–AML CPX-351–eligible high-risk AML. Consequently, CPX-351 eligibility in our study served as a marker of particularly aggressive disease biology. By examining CPX-351–eligible and CPX-351–noneligible AML separately, we aimed to clarify whether GVHD prevention strategies should be tailored to the underlying AML subtype, enhancing the clinical interpretability and translational relevance of our findings. Our findings will help inform evidence-based transplant care and provide a foundation for future intervention studies in the era of novel conditioning agents and therapeutics.

Methods

Study design and data source

This retrospective, multicenter cohort study analyzed outcomes in patients with high-risk AML who underwent their first allogeneic HCT using cord blood as the stem cell source. In this study, “high-risk AML,” including t-AML and AML-MRC, was defined in accordance with European Leukemia Net 2022 1 and World Health Organization 2022 10 recommendations, and eligibility for CPX-351 was determined in accordance with contemporary regulatory guidance. 9 This approach aligns with the international consensus that secondary AML comprises both t-AML and myeloid neoplasms progressing from antecedent myelodysplastic/myeloproliferative neoplasms or with specific myelodysplasia-related cytogenetic/molecular features. In this study, patients were stratified as t-AML vs non-t–AML for subgroup analyses. This stratification allowed for fair comparisons because patients with t-AML were uniformly CPX-351 eligible, whereas a subset of patients with newly diagnosed non-t–AML with AML-MRC were also eligible. CPX-351 eligibility highlights patients who are at high risk of relapses even after transplantation, making the evaluation of GVHD prophylaxis (CSP/TAC + MMF vs CSP/TAC + MTX) particularly meaningful in this subgroup. To provide clarity, a schematic comparison between traditional 7+3 induction chemotherapy and CPX-351 is shown in supplemental Table 1 to illustrate these therapeutic distinctions for general readers and multidisciplinary researchers.

Patient data were extracted from the Transplant Registry Unified Management Program database, which comprehensively registers physician-certified clinical data from >300 Japanese transplant centers. 11 , 12

Patient selection

This retrospective study included adult patients (aged ≥16 years) who underwent their first CBT for CPX-351–eligible high-risk AML between January 2010 and December 2023. High-risk AML subtypes were defined as t-AML, AML-MRC, AML secondary to myelodysplastic syndromes, AML evolving from myeloproliferative neoplasms, and AML arising from chronic myelomonocytic leukemia, according to the World Health Organization classification. 13 Eligible patients received GVHD prophylaxis with CSP/TAC + MMF or CSP/TAC + MTX. Only patients with sufficient follow-up data to evaluate neutrophil engraftment and acute GVHD were included. Patients with t-AML, who had a higher frequency of reduced-intensity conditioning than those with non-t–AML, previous solid tumor therapy, and an HCT-specific comorbidity index (HCT-CI) of ≥3, were analyzed separately. 14 GVHD prophylaxis outcomes (MMF vs MTX) were evaluated in the t-AML cohort and a combined non-t–AML cohort. The exclusion criteria were the receipt of antithymocyte globulin, a history of previous allogeneic transplantation, or any other investigator-determined ineligibility ( supplemental Figure 1 ).

GVHD prophylaxis and grouping

Patients were stratified by the following GVHD prophylactic regimen: (1) CSP/TAC + MMF and (2) CSP/TAC + MTX. Conditioning intensity (myeloablative vs reduced intensity) was classified using the Center for International Blood and Marrow Transplant Research criteria. 15

Definitions and outcomes

Neutrophil engraftment was defined as the first of 3 consecutive days with an absolute neutrophil count of ≥500/μL. Platelet engraftment was defined as the first of 7 consecutive days with a platelet count of ≥20 × 10 3 /μL without transfusion support. In both engraftment outcomes, point estimates and their ranges are presented as 95% confidence intervals (CIs). Primary graft failure was defined as the failure to achieve engraftment by day +35 after transplant. Acute GVHD was graded in accordance with established consensus criteria, and chronic GVHD was classified using National Institutes of Health guidelines. 16 , 17 The reported rates and their ranges of acute and chronic GVHD are shown as point estimates with 95% CIs. Transplant-related mortality (TRM) was defined as any death in continuous remission after HCT. Relapses were defined as recurrent AML or refractory disease after transplant. Survival end points were OS, disease-free survival (DFS), GVHD-free/relapse-free survival (GRFS), and chronic GVHD-free/relapse-free survival (CRFS). GRFS was defined as survival without grades 3/4 acute GVHD, moderate to severe chronic GVHD requiring systemic immunosuppression, relapse, or death. 18 CRFS was defined as survival without chronic GVHD requiring systemic immunosuppression, relapse, or death. 19 Point estimates for event proportions are uniformly presented with corresponding 95% CIs.

Statistical analysis

Descriptive statistics were calculated for all clinical variables. Categorical variables were compared using the Pearson χ 2 test, and continuous variables were compared using the Mann-Whitney U test. Cumulative incidence estimates for neutrophil engraftment, acute and chronic GVHD, TRM, and relapses accounted for competing risks using the Fine-Gray subdistribution hazard model, 20 and differences were evaluated using the Gray test. 21 Baseline covariates included in the multivariable analyses were age at the time of CBT (≥55 vs <55 years), sex (male vs female), Karnofsky performance status score (<80 vs ≥80), 22 disease status at CBT (complete remission [CR] vs non-CR), year of HCT (2010-2014 vs 2015-2023), the HCT-CI score (>2 vs ≤2; evaluated only in the non-t–AML group), conditioning regimen (reduced-intensity conditioning vs myeloablative conditioning), HLA-mismatched vs matched donor, and GVHD prophylaxis (MMF vs MTX).

In this cohort, standard donor-recipient HLA matching for CBT was primarily performed at the antigen level (low or intermediate resolution) for HLA-A, HLA-B, and HLA-DRB1 loci. Although allele-level HLA matching has become more prevalent in Japan in recent years, most cases in this study were based on antigen-level matching, with limited allele-level or HLA-C data annotated only in selected cases. Notably, differences in HLA matching methodology, particularly the use of antigen-level vs allele-level typing, can affect key outcomes, including the incidence of GVHD, engraftment, and OS. Accordingly, the technical aspects of HLA typing and matching were carefully considered when interpreting and comparing outcomes within our study with those from domestic or international registries that use differing standards.

Survival curves (OS, DFS, GRFS, and CRFS) were generated by the Kaplan-Meier method and compared using the log-rank test, supplemented by univariate and multivariate Cox proportional hazards regression. The 95% CIs for all probabilities and P values for pairwise comparisons were derived from pointwise estimates and calculated using standard techniques. In the statistical analyses, patients who failed to achieve a CR after induction therapy were classified as having “relapse at day 0,” which was defined as the initiation date of induction therapy. Therefore, nonremission after induction was considered equivalent to immediate relapse for the purposes of event-free survival and relapse-free survival analyses. This definition allowed for a comprehensive assessment of refractory and relapsed disease events.

Two-sided P values < .05 were considered significant. All statistical analyses were performed using Easy R (Saitama Medical Center, Saitama, Japan; http://www.jichi.ac.jp/saitama-sct/SaitamaHP.files/statmedEN.html ), 23 which is a graphical user interface for R (The R Foundation for Statistical Computing; www.r-project.org ) that extends the functionality of R Commander by adding statistical functions. Analyses were conducted using R version 4.3.1 and R Commander version 2.9-1.

All participating centers obtained informed consent in accordance with institutional and national ethical standards. The study protocol was approved by the data management committee of the Japanese Society for Hematopoietic Cell Transplantation and the institutional review board of St. Mary’s Hospital (approval number: 25-0511). This study was conducted in accordance with the Declaration of Helsinki.

Results

Patient and transplant characteristics

Among 3222 adult patients with t-AML (n = 423) and non-t–AML (n = 2799) who underwent their first CBT, baseline characteristics were mostly similar between the GVHD prophylaxis groups, except for age and sex ( Table 1 ). The median age exceeded 55 years in all cohorts, with a male predominance in patients with non-t–AML ( P = .016), and a lower HCT-CI in those with non-t–AML than in those with t-AML ( P < .001; supplemental Table 1 ). The conditioning regimen, cell dose, and donor HLA match rates were similar between the GVHD prophylaxis groups ( Table 2 ).

The distribution of primary malignancies preceding t-AML was heterogeneous. The most common antecedent malignancy in patients who developed t-AML was breast cancer, which was observed in 91 (21.5%) patients. Gastric cancer was the next most frequent malignancy (n = 12 [2.8%]), followed by ovarian cancer (n = 10 [2.4%]). A moderate number of patients had a history of other solid tumors, including ovarian cancer (n = 10 [2.4%]), esophageal cancer (n = 9 [2.1%]), colorectal cancer (n = 8 [1.9%]), and cervical cancer (n = 7 [1.7%]). Among hematological malignancies, large B-cell lymphoma (n = 16 [3.8%]) and follicular lymphoma (n = 13 [3.1%]) were the most commonly reported. Each of the other primary malignancies, such as endometrial cancer, seminoma, and multiple myeloma, accounted for ∼1% to 2% of cases. Additional rare diagnoses included malignant melanoma, germ cell tumors, head and neck cancers (pharyngeal, hypopharyngeal, and tongue), soft tissue sarcoma, and various hematological disorders (eg, acute lymphoblastic leukemia and blastic plasmacytoid dendritic cell neoplasm), with only 1 or a few cases found in each. In summary, most patients had a history of solid tumors before t-AML, whereas hematological malignancies were less common but remained an important subgroup.

The median follow-up was 28 to 63 months for survivors (range, up to 141 months). There were no significant differences in transplant characteristics (except for the conditioning regimen) or outcomes (except for the incidence of chronic GVHD and OS) between the t-AML and non-t–AML groups ( Table 2 ; supplemental Tables 2-4 ). MTX dosing for t-AML/non-t–AML in the study cohort was distributed as follows: 15 mg/m 2 , 10 mg/m 2 , and 10 mg/m 2 ; 10 mg/m 2 , 7 mg/m 2 , and 7 mg/m 2 ; and 5 or 7 mg/m 2 , 5 or 7 mg/m 2 , and 5 or 7 mg/m 2 on days 1, 3, and 5, respectively. These accounted for 17 (8%)/85 (6%), 160 (80%)/1240 (85%), and 24 (12%)/129 (9%) of the cases in each respective group. A reliable mutation status was unavailable for most patients because of the distribution of Fms-related receptor tyrosine kinase 3 (FLT3) internal tandem duplication mutations in our cohort (positivity, 7%; negativity, 11%; and 82% were not tested or had missing data) and FLT3 D835 mutations (positivity, 11%; negativity, 7%; and 82% were not tested or had missing data). Therefore, analyses regarding patient selection and characteristics based on the FLT3 mutation status were excluded from this study.

Hematopoietic recovery and incidence of GVHD

Neutrophil engraftment occurred significantly earlier in patients who received MMF (median, 19-20 days) than in those who received MTX (median, 20-21 days; P < .001; Table 3 ; Figure 1 A). There was no significant difference in platelet engraftment ( Figure 1 B). The cumulative incidence of engraftment by day 35 was significantly higher in patients who received MMF (85%-86%) than in those who received MTX (78%-82%; P = .031 in the t-AML subgroup and P < .001 in the non-t–AML subgroup). The incidence of grades 2 to 4 acute GVHD at 100 days was higher with MMF (47%-52%) than with MTX (29%-32%; P < .001; Figure 1 C). MMF prophylaxis resulted in a slightly higher cumulative incidence of chronic GVHD than MTX (27.5% vs 20%; P = .004; Figure 1 D). The type of disease (t-AML vs non-t–AML) did not affect engraftment or GVHD outcomes.

Survival and relapse or progression

At 2 years after transplant, the TRM rate was higher with MMF than MTX in the t-AML and non-t–AML groups (38%/34% vs 29%/26%; P < .001; Figure 1 E). Relapse or progression rates were similar across all groups (MMF, 41%-44% vs MTX, 42%-46%; P = .52; Figure 1 F). At 2 years after -transplant, OS rates were significantly higher with MTX than with MMF (42%-48% vs 38%-41%; P < .001). Additionally, DFS rates were significantly higher with MTX than with MMF (38%-43% vs 33%-37%; P = .003; Figure 1 G-H). The composite end points were also more favorable with MTX than with MMF (GRFS: MMF, 17%-18% vs MTX, 26%-28%; P < .001; CRFS: MMF, 11%-13% vs MTX, 20%-24%, P < .001; Figure 1 I-J).

Multivariable analysis

Multivariable Cox and Fine-Gray models identified age of ≥55 years (TRM: hazard ratio [HR], 1.47; OS: HR, 1.39), male sex (TRM: HR, 1.42; OS: HR, 1.42), Karnofsky performance status score of <80 at HCT (TRM: HR, 2.02), non-CR status at HCT (TRM: HR, 1.77), and a higher HCT-CI score (TRM: HR, 1.41) as independent predictors of inferior outcomes ( Table 4 ). The choice of MMF vs MTX had a modest effect on relapse-free survival after adjustment. The disease status at transplantation also predicted outcomes.

Infectious complications

Most patients in the t-AML and non-t–AML groups were seropositive for cytomegalovirus (CMV) before CBT, and 87% to 91% of patients with t-AML and 83% to 88% of those with non-t–AML tested positive for CMV immunoglobulin G. Seropositivity rates for hepatitis B virus, hepatitis C virus, HIV, and human T-cell leukemia virus type 1 were consistently low across all 4 prophylaxis groups, ranging between 0% and 7%. The prevalence of previous coronavirus disease 2019 infection at the time of transplantation was also low (<2% of patients overall). The frequency of posttransplant infectious complications was not significantly different between the t-AML and non-t–AML groups ( supplemental Table 5 ). Infectious complications after CBT were frequently observed in the t-AML and non-t–AML groups. Human herpesvirus 6 (HHV-6) encephalitis occurred significantly more often in patients who received MMF prophylaxis than in those who received MTX prophylaxis (10% in patients with t-AML who received MMF and 12% in those with non-t–AML who received MMF compared with only 2%-3% in patients who received MTX, P < .001). Bacteremia was common and affected 34% to 46% of patients across all groups. Candidemia developed in 3% to 5% of patients, whereas proven and probable invasive aspergillosis occurred in up to 6% of patients, with no significant differences between prophylactic regimens. Viral complications, such as BK polyomavirus– and JC polyomavirus–related hemorrhagic cystitis, as well as CMV antigenemia and colitis, were observed in 1% to 6% of patients. Notably, CMV antigenemia was significantly more frequent in those who received MTX than in those who received MMF (42% vs 31% in t-AML, 47% vs 41% in non-t–AML; P < .05). Overall, these data indicate that posttransplant infections, especially HHV-6 encephalitis and CMV reactivation, represent substantial complications and that their incidence is affected by the choice of GVHD prophylaxis.

Discussion

This nationwide, multicenter registry study provides real-world evidence from, to our knowledge, the largest Japanese cohort to date, showing unique insights into the efficacy and safety of CSP/TAC + MMF vs CSP/TAC + MTX as GVHD prophylaxis after CBT in high-risk AML, including t-AML and non-t–AML subtypes. Our findings from >3200 adults, with granular stratification of clinical backgrounds, highlight several key aspects distinct from previous reports. 7

Consistent with previous studies, 8 MMF-based regimens facilitated significantly faster neutrophil engraftment than MTX, which indicated more rapid immune reconstitution. However, this advantage of MMF was offset by a notably increased risk of grades 2 to 4 acute and chronic GVHD, which suggested a trade-off between hematopoietic recovery and early immune activation. Importantly, we found that despite a higher rate of GVHD with MMF, the TRM, relapse, and OS/DFS rates were similar between groups. This finding suggested that both protocols remained viable and that the optimal regimen should be individualized on the basis of the patients’ comorbidities, transplant characteristics, and center experience.

In this cohort, the accelerated immunosuppressive effect of MMF may have contributed to improved neutrophil engraftment; however, it was also associated with inadequate early control of T-cell alloreactivity, resulting in an increased rate of acute GVHD. In contrast, MTX has a more delayed onset than MMF but provides robust suppression of GVHD at the cost of delayed hematopoietic recovery and mucosal toxicity. Moreover, MMF regimens are increasingly adopted in haploidentical transplantation because of their benefits in immune reconstitution and reduction of chronic GVHD, although careful attention to acute complications is warranted. MMF’s rapid immunosuppressive effect likely contributes to faster engraftment but may not sufficiently control T-cell–mediated alloreactivity in the early posttransplant phase, leading to a higher rate of acute GVHD. 24 In contrast, MTX, a cytotoxic agent with delayed onset, has traditionally provided reliable GVHD suppression but can delay hematopoietic recovery. 7 As shown by previous studies on CBT and haploidentical HCT, MMF regimens are increasingly favored for facilitating immune reconstitution and reducing chronic GVHD, although acute risks remain. 25

An important observation of this study was the significantly elevated risk of HHV-6 encephalitis in MMF recipients. This elevated risk was found in the t-AML and non-t–AML groups, with an incidence rate in MMF recipients nearly 5 times that in MTX recipients. This real-world finding from a large Asian population corroborates and extends recent single-center 26 and international data 27 and has the following direct clinical implications. Early and stringent viral monitoring, especially for HHV-6, needs to be incorporated into supportive care protocols when choosing MMF as prophylaxis.

Our large-scale analysis also showed the heterogeneity inherent in the background of patients with high-risk AML, including differences in previous malignancies, disease status at transplant, the HCT-CI, and age. This finding emphasizes the necessity for selecting personalized prophylaxis and complication management strategies. Notably, the optimal total nucleated cell dose and HLA matching remain crucial for engraftment and survival, consistent with foundational registry studies. 27 In patients with high-risk AML lacking suitable donors, CBT remains a viable curative option. Both prophylaxis regimens deliver reliable hematopoietic recovery and survival.

High-dose MMF regimens are recommended when careful and proactive supportive care is available because these regimens are associated with lower rates of GVHD and infections. 28 The Japanese practice environment does not allow for high-dose MMF owing to insurance restrictions. Therefore, balancing the infectious risk with engraftment benefits remains a practical challenge that is unique to the Japanese context. MMF-based regimens may be favored for patients in whom rapid engraftment is less critical or the risk of infection is high. Additionally, achieving an optimal total nucleated cell dose (≥3 × 10 7 /kg) and HLA matching (≥4/6) remains essential for favorable outcomes, as supported by previous analyses. 29 , 30

This study has some strengths, including its large-scale, multi-institutional design, stringent statistical methodology, and comprehensive follow-up among Asian patients, providing a high level of evidence for benchmarking future studies, including essential pre–CPX-351. Nevertheless, limitations to the study, such as its retrospective nature, treatment variability across centers, lack of molecular data (eg, minimal residual disease), and challenges in capturing long-term outcomes for recent transplants, remain. Supportive care protocols, such as the introduction and increased use of letermovir during the study period, may have affected infection rates and outcomes. This temporal variability represents a limitation of our retrospective analysis. Notably, precise data regarding the dose and duration of MMF administration were not available in our study database. This lack of data represents an inherent limitation of our analysis because variations in immunosuppressive intensity and duration may affect transplant outcomes. We recommend that future studies incorporate detailed information on MMF dosing parameters to further clarify their effect in this setting. Based on the heterogeneity of conditioning regimens and MTX dosing in our cohort, future prospective studies focusing on more homogeneous groups may help provide clearer comparisons between GVHD prophylaxis strategies.

Our study grouped GVHD prophylaxis regimens according to the strategy of a calcineurin inhibitor plus MMF or MTX, without distinguishing between CSP and TAC. This approach was chosen because, in registry-based analyses, detailed recording of the calcineurin inhibitor subtype is often incomplete or heterogeneous across transplant centers and because the primary focus of our study was the comparison between MMF and MTX. Nevertheless, we acknowledge that there may be clinically relevant differences between CSP and TAC regarding the prevention of GVHD and other transplant outcomes. Inamoto et al demonstrated that TAC + MTX was associated with a lower mortality rate in unrelated donor recipients and with faster neutrophil recovery than CSP + MTX in HLA-identical settings. 31 Bug et al reported that, in the haploidentical transplant setting, TAC appeared to prevent severe acute GVHD more effectively than CSP, suggesting potential regimen-specific interactions with MMF that could be relevant for AML in CR. 32 Variation in the choice of calcineurin inhibitors among patients could have affected certain outcomes, particularly engraftment kinetics and the incidence of acute GVHD. Our analysis categorized patients only by the adjunct agent (MMF or MTX). Therefore, the effect of CSP vs TAC was not examined directly. Consequently, our results should be interpreted with the understanding that unmeasured heterogeneity in calcineurin inhibitor selection may act as a confounding factor. A dedicated subanalysis stratifying patients by the calcineurin inhibitor (CSP vs TAC) in combination with MMF or MTX could further refine interpretation of GVHD prevention strategies. However, the feasibility of evaluating long-term outcomes depends on the completeness of registry data capture. If sufficient case numbers are available, especially in the larger non-t–AML cohort, such an analysis would allow assessment of whether observed differences between MMF and MTX groups are consistent across CSP- and TAC-based strategies. The performance of this subanalysis may help clarify whether the apparent advantages of MMF over MTX (or vice versa) are universal or primarily driven by concomitant use with one calcineurin inhibitor. In situations in which the data are insufficient for a robust statistical comparison, we suggest acknowledging this limitation and considering the prospect of harmonized data capture in future studies.

This comprehensive nationwide analysis provides highly generalizable benchmarks for the efficacy and safety of current GVHD prophylaxis after CBT in adults with high-risk AML, while also identifying regimen-specific infectious risks and offering guidance for the practical management of posttransplant complications in real-world settings. Our findings lay the foundation for pivotal, prospective, multicenter trials in Japan and Asia, including those evaluating novel approaches, such as CPX-351-based conditioning, posttransplant cyclophosphamide, and JAK inhibitors. These findings will be invaluable for harmonizing cellular therapy protocols internationally. Future studies should particularly address the balance between the intensity of immunosuppression and graft-versus-leukemia efficacy, especially in molecularly high-risk subgroups, such as TP53-mutated AML, to advance individualized, risk-adapted prophylaxis and monitoring strategies in this challenging patient population.

Conflict-of-interest disclosure: The authors declare no competing financial interests.

Acknowledgments

The authors thank the patients and clinical staff for their participation in this study. They are grateful to the Japanese Data Center for Hematopoietic Cell Transplantation for assisting with the data management and to St. Mary’s Hospital for their editorial support. They also thank Ellen Knapp from Edanz for editing a draft of this manuscript.

This work was supported by the Practical Research Project for Allergic Diseases and Immunology (Research Technology of Medical Transplantation) of the Japan Agency for Medical Research and Development.

Authorship

Contribution: S.Y. contributed to the study design, data analysis, and manuscript preparation; M.Y., S.M., Y.S., T.T., K.H., J.K., Y.A., and T.K. contributed to the preparation of the manuscript; N.U., M. Tanaka, A.W., M.O., T.E., Y.U., S.T., T.I., N.D., M. Tokunaga, T.K., T.N., M.S.-Y., F.I., J.K., Y.A., and T.K. provided the clinical data; J.K., Y.A., and T.K. managed the clinical data; and all authors reviewed the manuscript.

Footnotes

The data analyzed in this study are not publicly available because of ethical restrictions that exceed the scope of the recipients’ or donors’ consent for research use in the registry. Data may be available from the corresponding author, Satoshi Yamasaki ( yamas009@gmail.com ), on reasonable request and with permission from the Japanese Society for Transplantation and Cell Therapy/Japanese Data Management Committee for Hematopoietic Cell Transplantation.

The full-text version of this article contains a data supplement.

Supplementary Material

Supplemental Tables and Figure

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