GVHD-free And Relapse-free Survival Research Articles

Haploidentical versus Cord Blood Transplantation in Pediatric AML. A Retrospective Outcome Analysis on Behalf of the Pediatric Subcommittee of GETH (Grupo Español de Trasplante Hematopoyético)

Haploidentical stem cell transplantation (Haplo-SCT) and cord blood transplantation (CBT) are both effective alternative treatments in patients suffering from acute myeloid leukemia (AML) and lacking a matched HLA donor. In the last years, many centers have abandoned CBT procedures mostly due to concern about poorer immune recovery compared with Haplo-SCT. We conducted a retrospective multicenter study comparing the outcomes using both alternative approaches in AML. A total of 122 transplants (86 Haplo-SCTs and 36 CBTs) from 12 Spanish centers were collected from 2007 to 2021. Median age at hematopoietic stem cell transplantation (HSCT) was 7 years (0.4-20). Thirty-nine patients (31.9%) showed positive minimal residual disease (MRD) at HSCT and a previous HSCT was performed in 37 patients (30.3%). The median infused cellularity was 14.4 × 106/kg CD34+ cells (6.0-22.07) for Haplo-SCT and 4.74 × 105/kg CD34+ cells (0.8-9.4) for CBT. Median time to neutrophil engraftment was 14 days (7-44) for Haplo-SCT and 17 days (8-29) for CBT (P = .03). The median time to platelet engraftment was 14 days (6-70) for Haplo-SCT and 43 days (10-151) for CBT (P < .001). Graft rejection was observed in 13 Haplo-SCTs (15%) and in 6 CBTs (16%). The cumulative incidence of acute graft versus host disease (GvHD) grades II-IV was 54% and 51% for Haplo-SCT and CBT, respectively (P = .50). The cumulative incidence of severe acute GvHD (grades III-IV) was 22% for Haplo-SCT and 25% for CBT (P = .90). There was a tendency to a higher risk of chronic GvHD in the Haplo-SCT group being the cumulative incidence of 30% for Haplo-SCT and 12% for CBT (P = .09). The cumulative incidence of relapse was 28% and 20% for Haplo-SCT and CBT, respectively (P = .60). We did not observe statistically significant differences in outcome measures between Haplo-SCT and CBT procedures: 5-year overall survival (OS) was 64% versus 57% (P = .50), 5-year disease-free survival (DFS) 58% versus 57% (P = .80), GvHD-free and relapse-free survival (GFRFS) 41% versus 54% (P = .30), and cumulative incidence of transplant-related mortality (TRM) 14% versus 15% (P = .80), respectively. In the multivariate analysis, MRD positivity and a disease status >CR1 at the time of HSCT were significantly associated with poorer outcomes (P < .05). In conclusion, our study supports that both haploidentical and cord blood transplantation show comparable outcomes in pediatric AML patients. We obtained comparable survival rates, although CBT showed a trend to lower rates of chronic GvHD and higher GFRFS, demonstrating that it should still be considered a valuable option, particularly for pediatric patients.

Anti-T-lymphocyte globulin improves GvHD-free and relapse-free survival in myelofibrosis after matched related or unrelated donor transplantation

Acute and chronic graft-versus-host disease (GvHD) are major complications of allogeneic hematopoietic cell transplantation (alloHCT). In vivo T-cell depletion with anti-T-lymphocyte globulin (ATLG) as part of the conditioning regimen prior to alloHCT is frequently used as GvHD prophylaxis, but data on its role in myelofibrosis is scarce. We took advantage of an international collaborative network to investigate the impact of ATLG in myelofibrosis undergoing first alloHCT. We included 707 patients (n = 469 ATLG and n = 238 non-ATLG prophylaxis). The cumulative incidence of acute GvHD grade II-IV was 30% for the ATLG group vs. 56% for the non-ATLG group (P < 0.001). Acute GvHD grade III-IV occurred in 20% vs. 25%, respectively (P = 0.01). Incidence of mild-to-severe chronic GvHD was 49% vs. 50% (P = 0.52), while ATLG showed significantly lower rates of severe chronic GvHD (7% vs. 18%; P = 0.04). GvHD-free and relapse-free survival (GRFS) at 6 years was 45% for the ATLG group vs. 37% for the non-ATLG group (P = 0.02), driven by significantly improved GRFS of ATLG in matched related and matched unrelated donors. No significant differences in risk for relapse, non-relapse mortality, and overall survival were observed. Multivariable modeling for GRFS showed a 48% reduced risk of GvHD, relapse, or death when using ATLG.

A Prospective, Multi-Center, Randomized, Controlled Clinical Trial to Explore the Role of Mesenchymal Stem Cells in Preventing Graft Versus Host Disease

Background: There are few studies currently available on the prevention of GVHD by mesenchymal stem cells (MSCs) that use a systematic approach to prevent both aGVHD and cGVHD simultaneously. The clinical investigation of MSCs preventing either aGVHD or cGVHD independently is the main focus of the earlier studies. Aim:Using the strategy of co-transplantation of MSCs and HSCs and phased application of MSCs after transplantation (MSCs 100-day scheme), we seek to develop a secure and dependable system that can avoid both aGVHD and cGVHD based on our preliminary research. Method:Patients undergoing haploidentical adult hematopoietic stem cell transplantation will receive unaltered, fourth-generation UC-MSCs(Umbilical Cord). In addition to the usual GVHD preventive measures, UC-MSCs are given four hours before the transplantation of peripheral blood stem cells on day 0. UC-MSCs are administered once weekly for 1-4 weeks, once every 2-8 weeks, and once every 4-12 weeks after transplantation. The dose needed for each transfusion is 1 10 6/kg. Our research will look at how well UC-MSCs prevent GVHD following haplo-HSCT, as well as recurrence rates after transplantation, transplant-related issues, and the state of immunological reconstruction. the frequency, severity, 1- and 2-year survival rates, cumulative death rates, and the occurrence of aGVHD and cGVHD.Real-time tracking will be performed to monitor the occurrence of aGVHD and cGVHD, as well as their severity, frequency, 1-year and 2-year survival rates, and cumulative mortality rates. The analysis of the differences between the control group and the experiment will take into account the pre-transplant ferritin levels, CMV serological status of the donor-recipient, blood type matching situation, HLA locus matching situation, disease remission status, residual disease conditions, recipient age, donor-recipient gender matching situation, stem cell quantities (nucleated cells and CD34+ cell counts), and stem cell numbers (nucleated cells and CD34+ cell counts). Results: 96 patients from the MSCs group and 96 patients from the control group are now accessible for statistical purposes. Demographic factors for age and gender distribution do not differ considerably. Acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome-EB2, and acute mixed cell leukemia,which were all classified as having the same level of risk. The cumulative incidence of aGVHD grades II to IV is 19.8% in the MSCs group, while grades III to IV is 0%. Comparable indications for the control group are 43.8% and 9.3%, respectively. The overall incidence of aGVHD differs between the two groups in a statistically significant way (P=0.0047). The rates of moderate and severe cGVHD in the control group were 10.4% and 9.4%, respectively, whereas they were 13.5% and 4.2% in the MSCs group. Over the course of 1 year, the cumulative incidence of cGVHD for the MSCs group was 36.5%, compared to 39.6% for the control group. Regarding the overall two-year OS, there is no discernible difference between the MSCs group and the control group (P=0.43).While the MSCs group outperformed the control group in terms of GRFS (GVHD free and relapse free survival). Conclusion: The strategy of MSCs 100-day scheme infusion can successfully lower the incidence of acute and chronic GVHD and is beneficial for enhancing patient GRFS.

ATG/ATLG Improves GvHD-Free and Relapse-Free Survival in Myelofibrosis Undergoing Hematopoietic Stem Cell Transplantation

Background Despite recent improvements in the field of JAK inhibitors, allogeneic hematopoietic stem cell transplantation (HSCT) remains the only potentially curative treatment for patients with myelofibrosis. However, HSCT is associated with a non-negligible treatment-related morbidity and mortality, with graft-versus-host disease (GvHD) being one of the major complications for these patients. In vivo T-cell depletion with antithymocyte/antilymphocyte globulin (ATG/ATLG, short ATG) as part of the conditioning regimen prior to HSCT is widely used as a GvHD prophylaxis, but data on its role in the setting of myelofibrosis is scarce. The aim of this study was to evaluate the impact of ATG on clinical outcomes of patients with myelofibrosis undergoing HSCT in a large international retrospective study. Patients and Methods We leveraged a multicenter collaborative network of 7 European and US academic transplant centers to accrue myelofibrosis patients who underwent first HSCT. The primary endpoint was GvHD-free and relapse-free survival (GRFS), whereas secondary endpoints were acute and chronic GvHD, relapse incidence, non-relapse mortality (NRM), and overall survival (OS). We applied multivariate Cox and Fine &amp; Gray modelling to adjust for potential confounders. In addition, a Dependent Dirichlet Process model for censored data was developed, which can adjust for potential violations of the ubiquitous proportional hazards assumption. Finally, to check results and to obtain another reliable comparison, we applied a propensity score matching of the two groups. Results Overall, we identified 806 patients, of whom 513 received ATG and 293 received non-ATG GvHD prophylaxis. No significant differences were observed between the two groups with regards to median age at HSCT (57 years for both) nor for gender, disease ontogenesis (primary or secondary), frequency of driver mutations, and treatment with ruxolitinib prior to transplant. Patients in the ATG and the non-ATG group differed for other characteristics including splenectomy prior to transplant (8% vs. 20%), donor type (matched related donor (MRD): 21% vs. 39%), Karnofsky Performance Status (&amp;lt;90%: 39% vs. 26%), intensity of conditioning therapy (reduced intensity conditioning (RIC) in 80% vs. 40%) and the presence of constitutional symptoms (58% vs. 44%). Regarding the Dynamic International Prognostic Scoring System (DIPSS), the ATG cohort was more enriched in intermediate-2 and high-risk diseases (64% vs. 58%). Notably, the most common stem cell source in the ATG and the non-ATG cohort was in both cases peripheral blood (98% vs. 95%). The cumulative incidence of acute GvHD grade II-IV was 35% (95% CI, 31-39%) for the ATG group vs. 58% (95% CI, 52-64%) for the non-ATG group (P&amp;lt;0.001). No difference in incidence of chronic GvHD was observed, showing 53% (95% CI, 49-57%) for the ATG group vs. 52% (95% CI, 47-57%) for the non-ATG group (P=0.52). With a median follow-up of 6.5 years for the ATG group and 7 years for the non-ATG group (P=0.10), the 5-year estimates for GRFS were 47% (95% CI, 43-51%) vs. 44% (95% CI, 38-50%; P=0.007; Figure), respectively. The 5-year cumulative incidence of relapse was 14% (95% CI, 10-18%) vs. 13% (95% CI, 8-18%; P=0.62) and the 5-year cumulative incidence of death without relapse for both groups was 28%, respectively (P=0.59). Remarkably, 5-year OS was similar, being 63% (95% CI, 59-67%) for the ATG group vs. 62% (95% CI, 58-68%) for the non-ATG group (P=0.56). Multivariable modelling for GRFS (adjusting for donor type, performance status, conditioning intensity, and DIPSS categories) showed an independent significant reduction in risk for GvHD or relapse in the ATG group (HR=0.85, 95% CI 0.79-0.91; P=0.007). Propensity score matching of 150 pairs confirmed the significant effect of ATG on GRFS (HR 0.90, 95% CI, 0.82-0.98; P=0.03). No differences between the two groups were identified for secondary endpoints of relapse, non-relapse mortality, and overall survival. Conclusion The use of ATG as GvHD prophylaxis in patients with myelofibrosis undergoing HSCT resulted in significantly reduced GRFS. This effect was mainly driven by a significant reduction in acute GvHD.

Phase II Multicenter, Randomized Controlled Study on Infusion of MSCs at 45 Days after Haplo-Hematopoietic Stem Cell Transplantation in the Prophylaxis of Gvhd

Background: Haploidentical hematopoietic stem-cell transplantation (haplo-HSCT) has successfully solved the problem of donor shortness. However, the increased risk of GVHD and the increased incidence of relapse after the administration of immune depressors for GVHD treatment have significantly influenced the quality of life of patients. Therefore, to prevent GVHD in patients who received haplo-HSCT, we designed a clinical trial that evaluated repeated infusions of UC-MSCs from day 45 after haplo-HSCT to prevent GVHD. Methods: A total of 148 qualified subjects aged between 18 and 60 with haplo-HSCT in five transplant centers in the Midwest of China were enrolled and randomly assigned equally into the MSC group and the control group. The patients in the MSC group received 4 rounds of UC-MSC infusions (1×106 cells/kg every two weeks from 45 days after transplantation) and a regular GVHD prophylaxis regimen, while the patients in the control group received only a regular GVHD prophylaxis regimen. The incidence and severity of cGVHD was the primary endpoint, and the incidence and severity of aGVHD, GVHD-free and relapse-free survival (GRFS), cumulative relapse rate, overall survival (OS), progression-free survival (PFS) and transplantation complications were recorded to measure the efficacy of MSCs in GVHD prophylaxis. Results: The overall incidence of cGVHD was 27% after MSC infusion and 43.2% in the control group (P=0.0388). The incidences of severe cGVHD and III-IV aGVHD in the patients in the MSC group were significantly decreased to 5.4% and 2.7%, respectively, while that in the control group they were 17.5% and 13.5%, respectively (P=0.0096 and P=0.0094). There was no significant difference in the cumulative relapse rate, OS or PFS between the two groups (P=0.6481, P=0.1980 and P= 0.3346). Conclusion: In this trial, we indicated that early repeated infusions of UC-MSCs effectively decreased the incidence and severity of cGVHD, and the incidence and severity of aGVHD manifested as an improved GRFS rate for patients after haplo-HSCT. Therefore, MSC infusion is an effective GVHD prophylaxis method after haplo-HSCT. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

High Risk of Recurrence of Malignancy Noted in Four-day rATG Regimen After Allogeneic PBSCT From Matched Sibling Donors

Hitherto, the optimal timing of rabbit anti-thymocyte globulin (rATG) in matched sibling donor peripheral blood stem cell transplantation (MSD-PBSCT) remains to be elucidated. We wanted to evaluate the effect of a new timing strategy of rATG in MSD-PBSCT patients on transplantation outcomes. In this prospective single-arm phase 2 clinical trial, 45 consecutive MSD-PBSCT patients were enrolled from February 1, 2019, to January 31, 2021. The rATG was administered intravenously at a total dose of 5 mg/kg from day −5 to day −2 before graft infusion (4d-ATG group). Thirty-seven MSD-PBSCT patients receiving rATG at the same total dose of 5 mg/kg from day −5 to day −4 before graft infusion from December 1, 2014, to January 31, 2019 served as historical control (2d-ATG group). No graft failure occurred in either group. In the 4d-ATG group, median timing to neutrophil and platelet engraftment was 12 days. The cumulative incidences (CI) of grade 2-4 and grade 3-4 acute graft-versus-host disease (GVHD) at day 100 were 37.8% and 4.4%. The 2-year CIs of severe chronic GVHD and extensive chronic GVHD were 2.2% and 9.6%. The rates of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) reactivation at day 180 were 24.4% and 37.8%, respectively. No patients died of non-relapse causes. Twenty-one patients relapsed at a median of 203 days after transplantation, and the 2-year cumulative incidence of relapse (CIR) was 51.4%. The 2-year probabilities of overall survival (OS), disease-free survival (DFS), and GVHD-free and relapse-free survival (GRFS) were 72.4%, 48.6%, and 40.8%, respectively. There were no significant differences between the 4d-ATG group and 2d-ATG group with regard to timing of neutrophil and platelet engraftment, incidences of CMV reactivation, EBV reactivation, acute GVHD, chronic GVHD, probabilities of OS, and GRFS. The 2-year CIR was significantly increased, and the 2-year DFS was significantly reduced in 4d-ATG group compared with the control group (CIR: 51.4% versus 13.5%, P < .001; DFS: 48.6% versus 75.7%, P = .014). High CIR and worse DFS were noted in MSD-PBSCT receiving 4d-ATG regimen compared with historical control (2d-ATG regimen). Inappropriate rATG timing may increase the risk of relapse after MSD-PBSCT in patients with hematologic malignancies.© 2023 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Anti-thymocyte globulin with CsA and MMF as GVHD prophylaxis in nonmyeloablative HLA-mismatched allogeneic HCT.

Nonmyeloablative regimens are used for allogeneic hematopoietic cell transplantation (HCT) of older or medically unfit patients, but successful outcome is still hindered by graft-versus-host disease (GVHD), especially in the setting of HLA-mismatched HCT. New GVHD prophylaxis strategies are emerging, including the triple drug strategy, that improve the GVHD-free and relapse-free survival (GRFS). Because the impact of ATG in HLA-mismatched Flu-TBI-based nonmyeloablative HCT has not been investigated, we did a retrospective analysis in three Dutch centers. 67 patients were evaluable, with a median age of 56 years. Overall survival, relapse-free survival and GRFS at 4 years were 52%, 43%, and 38%, respectively. NRM findings and cumulative incidence of relapse at 4 years were 26% and 31%, respectively. At 1-year grade II-IV had occurred in 40% of the patients, and the incidence of moderate-severe chronic GVHD incidence was 16%. Acknowledging the limitations of retrospective analyses, we conclude that the use of ATG for HLA-mismatched truly nonmyeloablative Flu-TBI HCT is feasible and results in acceptable long term outcomes, especially with regards to GRFS. We consider ATG in combination with cyclosporin and mycophenolate mofetil as an alternative for the triple drug strategy that uses sirolimus for GVHD prophylaxis in this particular setting.

Role of pretransplant anti‐thymocyte globulin in matched sibling donor stem cell transplantation after reduced intensity conditioning for myelodysplastic syndrome

We investigated the role of anti-thymocyte globulin (ATG; Thymoglobulin) in matched sibling donor hematopoietic stem cell transplantation (MSD-HSCT) after reduced intensity conditioning (RIC) in myelodysplastic syndrome (MDS). Forty-seven patients with 10mg/kg ATG (ATG group; median age 53years) and 33 without ATG (no-ATG group; median age 43, P<.0001) were compared. Median time to engraftment was similar. Two-year cumulative incidence of moderate-to-severe chronic graft-versus-host disease (GVHD) was significantly lower in the ATG group (15% vs 55%, P<.0001), while that of acute GVHD was similar compared with the no-ATG group. After a median follow-up of 60months (range, 14-184), the 3-year cumulative incidences of non-relapse mortality and relapse were 9% and 21% for ATG group and 15% and 19% for no-ATG group (P=.408 and P=.717), respectively, leading to a significantly better 3-year GVHD-free and relapse-free survival (GRFS) in the ATG group (55% vs 19%, P=.006): The 3-year overall and disease-free survival were similar. Infectious complication occurred with similar frequencies in both groups. These findings suggest that ATG can be safely used to decrease moderate-to-severe chronic GVHD with improved GRFS for patients with MDS receiving MSD-HSCT in RIC setting.

The Efficacy of Risk Score System Establishment and Methylprednisolone Stratification Treatment for Pre-Engraftment Syndrome after Unrelated Cord Blood Transplantation: A Retrospective (development) and a Prospective (validation) Study

Introduction Pre-engraftment syndrome (PES) is a common immune reaction prior to neutrophil engraftment after unrelated cord blood transplantation (UCBT), with a unique clinical manifestation of non-infectious fever and skin rash. The reported incidence of PES ranges from 20% to 78%. Although many researchers believe that PES is associated with a high incidence of acute graft-versus-host disease (GVHD) but not with transplant-related mortality (TRM) , relapse, or overall survival (OS), they did not stratify the risk factors of PES, and how to carry out different doses of methylprednisolone (MP) stratified intervention therapy still remains unknown. Method s First, 136 hematological malignancy patients treated with UCBT from April 2000 to February 2012 in our transplantation center were retrospectively analysis. Among them, 92 patients occurred PES. High-risk factors for 180-day TRM in PES patients were established by univariate and multivariate analysis. Then, from January 2013 to August 2016, 221 PES patients were scored according to the risk scoring system and stratified treated with different doses of MP. Finally, in order to validate the efficacy of MP stratification treatment, we conducted a prospective, open label and non-randomized clinical trial including 240 PES patients who underwent UCBT from September 2016 to December 2018. This trial is registered at www.chictr.org.cn as ChiCTR-ONC-16009013. Results The cumulative incidence of neutrophil and platelet engraftment was significantly higher in PES group than non-PES group (97.8% vs 70.5%, P&lt;0.001; 75.0% vs 54.5%, P=0.05). In 92 PES patients, multivariate analysis showed that failed MP treatment, multiple clinical symptoms and early onset of PES were independent high risk factors affecting180-day TRM. One high risk factor was scored as 1. The 92 PES patients were divided into PES-0, PES-1,PES-2 and PES-3, and the higher the score, the higher the TRM (17.7% vs 21.9% vs 62.5% vs 100%,respectively; P&lt;0.001), and the lower the OS (68.3% vs 56.2% vs 25.0% vs 0%, respectively; P&lt;0.001). Then, from January 2013 to August 2016, 221 PES patients were scored as PES-0, PES-1 and PES-2 according to the following two high risk factors (multiple clinical symptoms and early onset of PES) and stratified treated with different doses of MP (0.5mg/kg/d for PES-0, 1mg/kg/d for PES-1 and 2mg/kg/d for PES-2). Compared to the previous PES patients with the same risk score, the 180-day TRM of PES-1 and PES-2 patients was significantly reduced and the OS, disease free survival (DFS), and GVHD-free and Relapse-free survival (GRFS) were significantly increased after stratified treatment. The results in the prospective trial were similar to the retrospective study. In addition, although stratified therapy could significantly improve the prognosis of PES-2 patients cohort, the cumulative incidence of acute GVHD and GRFS are still the worst compared with other risk score patients. Therefore, how to improve the outcomes of PES-2 patients remains to be further studied. Conclusion s PES after UCBT is benefit for engraftment, but should be graded according the risk scoring system. Different doses of MP stratified intervention therapy can significantly improve the prognosis of severe PES patients. The risk scoring system of PES after UCBT and MP stratification treatment are worthy of clinical application. But the cumulative incidence of acute GVHD and GRFS in severe PES patients still need to be ameliorated in the further study. Disclosures No relevant conflicts of interest to declare.

Allogeneic peripheral blood stem cell transplantation with anti-thymocyte globulin versus allogeneic bone marrow transplantation without anti-thymocyte globulin.

We compared severe graft-versus-host-disease (GvHD) free and relapse-free survival and other transplantation outcomes of acute myeloid leukemia (AML) patients given bone marrow (BM) without anti-thymocyte globulin (ATG) versus peripheral blood stem cells (PBSC) with ATG after myeloablative conditioning. In the cohort of patients receiving grafts from a human leukocyte antigen (HLA)-matched sibling donor, patients given PBSC with ATG (n=1,021) and those given BM without ATG (n=1,633) presented comparable severe GvHD-free relapse-free survival (GRSF)(hazard ratio [HR]=0.9, 95% confidence interval [CI]: 0.8-1.1, P=0.5) and overall survival (HR=1.0, 95% CI: 0.8-1.2, P=0.8). They had however, a lower incidence of chronic GvHD (cGvHD) (HR=0.7, 95% CI: 0.6-0.9, P=0.01). In the cohort of patients receiving grafts from HLA-matched unrelated donor , patients given PBSC with ATG (n=2,318) had better severe GvHD-free and relapse-free survival (GRFS) than those given BM without ATG (n=303) (HR=0.8, 95% CI: 0.6-0.9, P=0.001). They also had a lower incidence of cGvHD (HR=0.6, 95% CI: 0.5-0.8, P=0.0006) and better overall survival (HR=0.8, 95% CI: 0.6-1.0, P=0.04). In summary, these data suggest that PBSC with ATG results in comparable (in the case of sibling donor) or significantly better (in the case of unrelated donor) severe GRFS than BM without ATG in patients with AML in complete remission receiving grafts after myeloablative conditioning.

FLT3 ligand plasma levels have no impact on outcomes after allotransplant in acute leukemia

ObjectiveThis study was designed to assess the impact on outcomes of early soluble Fms-like tyrosine kinase 3 ligand concentrations (sFLc) in patients receiving an allogeneic hematopoietic stem cell transplantation (allo-HSCT) for acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). MethodsThis was a prospective monocentric study including all allo-HSCT patients included in the previous FLAM/FLAL study (Peterlin et al., 2019). Blood samples collected before the start of conditioning then post-transplant were frozen, stored and tested by ELISA. The parameters considered were hematopoietic recoveries, Leukemia Free Survival and Overall Survival, acute and chronic GVHD, grade 3 or 4 acute and/or extensive chronic GVHD-free and relapse-free survival (GRFS). ResultsForty-one patients were included, a total of 179 samples were assayed for sFLc. There was no impact of sFLc levels (<=median vs> median) on acute and chronic GVHD incidences, LFS, OS nor GRFS. ConclusionAt variance with induction results for AML (Peterlin et al., 2019) endogenous sFLc do not appear to be a prognostic marker at the time of or after allo-HSCT. Even though the results are negatives, this is, to the best of our knowledge, the only prospective series specifically addressing the question of sFLc impact after allo-HSCT in acute leukemias.

Comparison of umbilical cord blood transplantation and hematopoietic stem cell transplantation from HLA-matched sibling donors in the treatment of myelodysplastic syndrome-EB or acute myeloid leukemia with myelodysplasia-related changes

目的比较非血缘脐血干细胞移植（UCBT）与同胞HLA全相合供者造血干细胞移植（MSD-HSCT）治疗骨髓增生异常综合征伴原始细胞增多（MDS-EB）和急性髓系白血病伴骨髓增生异常相关改变（AML-MRC）的临床疗效。方法回顾性分析2011年2月至2017年12月接受UCBT/MSD-HSCT的MDS-EB/AML-MRC患者64例，其中MDS-EB 38例，AML-MRC 26例。结果①与MSD-HSCT组比较，UCBT组AML-MRC患者比例较高[52.8%（19/36）对25.0%（7/28），P=0.025]，中位年龄较低[13（1.5~52）岁对32（10~57）岁，P=0.001]。②UCBT组与MSD-HSCT组+42 d粒细胞植入率均为100%，中位植入时间分别为17.5（11~31）d、11.5（10~20）d；UCBT组+100 d血小板植入率为91.4%，中位植入时间为40（15~96）d，MSD-HSCT组+100 d血小板植入率为100.0%，中位植入时间为15（11~43）d。③UCBT组和MSD-HSCT组比较，+100 dⅡ~Ⅳ度、Ⅲ/Ⅳ度急性GVHD累积发生率、180 d移植相关死亡率、3年累积复发率、3年总生存率和3年无病生存率差异均无统计学意义（P>0.05）。④UCBT组3年慢性GVHD、重度慢性GVHD的累积发生率均低于MSD-HSCT组[28.3%（95% CI 13.4%~45.3%）对67.9%（95%CI 46.1%~82.4%），P=0.002；10.3%（95%CI 2.5%~24.8%）对50.0%（95%CI 30.0%~67.1%），P<0.001]；UCBT组3年无严重急慢性GVHD及无复发生存（GRFS）率明显高于MSD-HSCT组[55.0%（95%CI 36.0%~70.6%）对28.6%（95%CI 13.5%~45.6%），P=0.038]。结论UCBT治疗MDS-EB/AML-MRC患者可获得比MSD-HSCT更好的移植后生存质量。

Antithymocyte globulin improves GVHD-free and relapse-free survival in unrelated hematopoietic stem cell transplantation.

Antithymocyte globulin (ATG) is an important component of conditioning regimens to prevent graft-versus-host disease (GVHD) in unrelated hematopoietic stem cell transplantation (HSCT), but the optimal dose of ATG remains unknown. We prospectively analyzed 205 unrelated HSCTs in patients with malignant hematological disorders. HSCTs were classified as follows: HLA-matched transplant without ATG (n = 53, group A), HLA-mismatched transplant treated with 6.0 mg/kg thymoglobulin (n = 77, group B), and HLA-matched transplant treated with 4.5 mg/kg thymoglobulin (n = 75, group C). For groups A and B, the 5-year moderate/severe chronic GVHD rates were 31.9% and 24.2%, the 5-year GVHD-free and relapse-free survival (GRFS) rates were 28.3 and 47%, and the 2-year immunosuppressive therapy (IST)-free survival rates were 8.6% and 40.2% (p = 0.0016), respectively. Furthermore, group C had lower incidences of grade II-IV acute GVHD (18.7%) and 5-year moderate/severe chronic GVHD (16.6%) than group A did. Group C had higher 5-year GRFS (52.1% vs 28.3%, p = 0.002), 2-year IST-free survival (51.7% vs 8.6%, p = 0.00004), and 5-year overall survival (OS) (68.3% vs 41.5%, p = 0.007) rates than group A did. Thus, ATG was associated with better GVHD prevention, a higher rate of IST-free survival, lower transplant-related mortality (TRM), and superior OS and GRFS in unrelated HSCTs.

Differential Outcomes for Ex Vivo Versus In Vivo Alloreactive T-Cell Depletion Strategies in Haploidentical HSCT

Introduction In haploidentical allogeneic hematopoietic stem cell transplantation (haplo-HSCT), different strategies are used to eliminate alloreactive T cells, one of which can be performed in vivo early after T-cell-replete haplo-HSCT using post-transplant cyclophosphamide (PTCy). Currently under development is T-cell-depleted haplo-HSCT supplemented with T-lymphocytes that are depleted ex vivo of their alloreactive component (ATIR101; Kiadis Pharma). Both strategies are promising, but comparisons of clinical outcomes obtained in similar patient populations have not been performed. Methods Data from published retrospective studies were analyzed to assess clinical outcomes of haplo-HSCT plus PTCy, and 1-year outcomes were compared with a pooled analysis of 2 phase II clinical trials of a single dose of ATIR101 in 37 AML/MDS/ALL patients. Studies in which PTCy was used in patient populations with >50% AML/MDS/ALL were identified (Table). The 1-year rates of relapse, relapse-related mortality (RRM), non-relapse mortality (NRM), graft-versus-host disease (GVHD), and overall survival (OS) for the ATIR101 clinical trials were compared with the weighted average of these outcomes for the identified studies. Differences in disease risk index (DRI) between PTCy and ATIR101 study populations were adjusted according to the relationship between DRI and OS. Finally, PTCy studies reporting GVHD-free and relapse-free survival (GRFS) were identified. One-year GRFS rates from 2 haplo-HSCT plus PTCy studies reporting DRI status were also normalized according to the DRI profile in the ATIR101 clinical trials to allow comparison. Results The weighted average of PTCy outcomes in populations with >50% AML/MDS/ALL vs ATIR101 patient outcomes were 29% vs 8% for relapse; 18% vs 8% for RRM; 22% vs 33% for NRM; 5% vs 5% for acute GVHD grade III/IV; 24% vs 3% for chronic GVHD; and 60% vs 58% for OS. The OS in DRI-adjusted studies for PTCy was similar to that in ATIR101 clinical trials (63% vs 58%, respectively, Table). One-year GRFS rates for PTCy were 33% (95% CI: 25–41) (Solh 2016), 45% (95% CI: 40–50) (McCurdy 2017), and 33% (average) (Santoro 2017). The DRI profile was more favorable than in the ATIR101 studies and the normalized 1-year GRFS rates were reduced to 30% (Solh 2016) and 40% (McCurdy 2017). In patients intended to receive a single dose of ATIR101 after haplo-HSCT, 1-year GRFS estimate was 53% (95% CI 39–72). Conclusion Although not a head-to-head comparison, these cross-study analyses provide first insights into a potential advantage of ex vivo (ATIR101) over in vivo (PTCy) depletion of alloreactive T cells, including but not limited to rates of relapse, chronic GVHD, and GRFS. A large, phase III, randomized control trial is underway to assess the relative safety and efficacy of ATIR101 after T-cell-depleted haplo-HSCT versus PTCy after T-cell-replete haplo-HSCT (CR-AIR-009 HATCY; NCT02999854).

Depletion of Alloreactive T Cells after Haploidentical HSCT: Comparison of Outcomes for Ex Vivo Versus In Vivo Treatment Strategies

Background: The use of haploidentical allogeneic hematopoietic stem cell transplantation (haplo-HSCT) has increased owing to therapeutic advances that have mitigated the main barriers such as high incidence of graft-versus-host disease (GVHD) and non-relapse mortality (NRM). This is primarily attributable to the elimination of alloreactive T cells in either the patient or the graft. Such T-cell depletion can be performed in vivo early after T-cell-replete haplo-HSCT using post-transplant cyclophosphamide (PTCy). Alternatively, T-cell-depleted haplo-HSCT can be supplemented with T-lymphocytes that are depleted ex vivo of their alloreactive component in the form of ATIR101 (Kiadis Pharma). Patient exposure to PTCy to eliminate donor alloreactive cells can be performed easily and at low cost but may cause patient toxicity and increase relapse rates, and it requires post-transplant immune suppression. Although ATIR101 requires cell manufacturing and is more expensive, it limits toxicity to the patient, enables haplo-HSCT without the use of immunosuppressants, and may reduce relapse rates. Both strategies are promising, but no attempt has yet been made to compare clinical results in similar patient populations to delineate key features of alloreactive T-cell depletion performed either ex vivo or in vivo.Methods: Data from published retrospective studies (single-site or registry data) were analyzed to assess clinical outcomes of haplo-HSCT plus PTCy. The 1-year outcomes from these studies were compared with results from a pooled analysis of 2 phase II clinical trials of a single dose of ATIR101 (N=37, all patients with AML/MDS/ALL [CR-AIR-007, CR-AIR-008]). Studies in which PTCy was used in patient populations with >50% AML/MDS/ALL were identified (Ciurea 2015, Piemontese 2017, Solomon 2012, Ciurea 2012, Devillier 2015, Di Stasi 2014, Esquirol 2016, Sugita 2015). The 1-year rates of relapse, relapse-related mortality (RRM), NRM, GVHD, and overall survival (OS) for the ATIR101 clinical trials were compared with the weighted average of these outcomes for the identified studies. OS is known to correlate with disease risk index (DRI; Armand 2014); therefore, publications reporting both OS and DRI (McCurdy 2017, Ciurea 2015, Devillier 2015, Sugita 2015) were identified to compare OS. Differences in DRI between PTCy and ATIR101 study populations were adjusted according to the relationship between DRI and OS. Finally, PTCy studies reporting GVHD-free and relapse-free survival (GRFS) were identified (Solh 2016, McCurdy 2017, Santoro 2017). There is a clinically relevant and statistically significant correlation between GRFS and DRI, so 1-year GRFS rates from the 2 studies reporting DRI status (Solh 2016, McCurdy 2017) were also normalized according to the DRI profile in the ATIR101 clinical trials to allow comparison.Results: The weighted average of PTCy (N=571) outcomes in populations with >50% AML/MDS/ALL vs ATIR101 patient outcomes were: 29% vs 8% for relapse; 18% vs 8% for RRM; 22% vs 33% for NRM; 5% vs 5% for acute GVHD grade III/IV; 24% vs 3% for chronic GVHD; and 60% vs 58% for OS. The OS in DRI-adjusted studies for PTCy (N=561) was similar to that in ATIR101 clinical trials (63% vs 58%, respectively). The GRFS-reporting studies included a total of 708 patients (Sohl 2016, N=128; McCurdy 2017, N=372; Santoro 2017, N=208); 1-year GRFS rates for PTCy in these studies were 33% (95% CI: 25-41), 45% (95% CI: 40-50), and 33% (average), respectively. In the 2 studies reporting DRI (N=500), the DRI profile was more favorable than in the ATIR101 studies and the 1-year GRFS rates normalized in line with the ATIR101 studies were reduced to 30% (Sohl 2016) and 40% (McCurdy 2017). In patients intended to receive a single dose of ATIR101 after haplo-HSCT, Kaplan-Meier estimate of 1-year GRFS was 53% (95% CI 39-72) (Table 1).Conclusion: This is not a head-to-head comparison, so data should be interpreted with caution. However, in these cross-study analyses, first insights into a potential advantage of ex vivo (ATIR101) over in vivo (PTCy) depletion of alloreactive T cells is suggested, including but not limited to rates of relapse, chronic GVHD, and GRFS. A large, phase III, randomized control trial is thus underway to assess the relative safety and efficacy of ATIR101 after T-cell-depleted haplo-HSCT versus PTCy after T-cell-replete haplo-HSCT (CR-AIR-009 HATCY; NCT02999854). [Display omitted] DisclosuresDevine:Kiadis Pharma: Consultancy. Mielke:Kiadis Pharma: Other: Travel grants, Research Funding. Tuk:Kiadis Pharma: Consultancy. Meewisse:Kiadis Pharma: Employment. Sandler:Kiadis Pharma: Employment. Roy:University of Montreal: Patents & Royalties: Author on patent; Kiadis Pharma: Other: Travel support; Hopital Maisonneuve Rosemont: Patents & Royalties: Author on patent.

Measurable residual disease, conditioning regimen intensity, and age predict outcome of allogeneic hematopoietic cell transplantation for acute myeloid leukemia in first remission: A registry analysis of 2292 patients by the Acute Leukemia Working Party European Society of Blood and Marrow Transplantation.

Patients with acute myeloid leukemia (AML) in morphological first complete remission (CR1) pre-allogeneic hematopoietic cell transplantation (HCT) may have measurable residual disease (MRD) by molecular and immunophenotyping criteria. We assessed interactions of MRD status with HCT conditioning regimen intensity in patients aged <50 years (y) or ≥50y. This was a retrospective study by the European Society for Blood and Marrow Transplantation registry. Patients were >18y with AML CR1 MRD NEG/POS and recipients of HCT in 2000-2015. Conditioning regimens were myeloablative (MAC), reduced intensity (RIC) or non-myeloablative (NMA). Outcomes included leukemia free survival (LFS), overall survival (OS), relapse incidence (RI), non-relapse mortality (NRM), chronic graft-vs-host (cGVHD), and GVHD-free and relapse-free survival (GRFS). The 2292 eligible patients were categorized into four paired groups: <50y MRD POS MAC (N = 240) vs RIC/NMA (N = 58); <50y MRD NEG MAC (N = 665) vs RIC/NMA (N = 195); ≥50y MRD POS MAC (N = 126) vs RIC/NMA (N = 230), and ≥50y MRD NEG MAC (N = 223) vs RIC/NMA (N = 555). In multivariate analysis RIC/NMA was only inferior to MAC for patients in the <50y MRD POS group, with worse RI (HR 1.71) and LFS (HR 1.554). Patients <50Y MRD NEG had less cGVHD after RIC/NMA HCT (HR 0.714). GRFS was not significantly affected by conditioning intensity in any group. Patients aged <50y with AML CR1 MRD POS status should preferentially be offered MAC allo-HCT. Prospective studies are needed to address whether patients with AML CR1 MRD NEG may be spared the toxicity of MAC regimens. New approaches are needed for ≥50y AML CR1 MRD POS.

Low-Dose Anti-T Lymphoglobulin as Prophylaxis for Graft-versus-Host Disease in Unrelated Donor Transplantations for Acute Leukemias and Myelodysplastic Syndromes

Chronic graft-versus-host disease (cGVHD) is a major complication after stem cell transplantation (HSCT). Several randomized studies already demonstrated that anti-T lymphoglobulin (ATLG) is effective in preventing GVHD after myeloablative unrelated and HLA-identical sibling transplants. However, the issue of doses and the potential increase of relapses still remain unsolved. Here we report data on 190 patients with acute leukemia and myelodysplastic syndrome who underwent an unrelated HSCT with low-dose ATLG (15 to 30 mg/kg) given at an earlier timing (days –6 to –2). HSCT was performed from HLA 10/10 (n = 62, 33%), 9/10 (n = 91, 48%), 8/10 (n = 30, 16%), and <8/10 (n = 7, 4%) identical unrelated donor. Peripheral blood was the stem cell source in 42% (n = 80). Median follow-up was 51 months. Grades II to IV and III to IV acute GVHD were 26% and 9%, respectively, and 2-year overall and moderate to severe cGVHD were 23% and 14%, respectively. The 3-year incidences of relapse and nonrelapse mortality were 26% and 18%, respectively. The rates of 3-year overall survival (OS), disease-free survival (DFS), and GVHD-free and relapse-free survival (GRFS) were 60%, 56% and 44%, respectively. Factors such as younger donor, good performance status, and early disease were associated with better outcome in terms of OS, DFS, and GRFS. Our data indicate that doses of ATLG lower that those used in randomized clinical trials can be used for GVHD prevention, even in the adult setting, without clear increases in relapse and infections; these findings need to be further validated by a prospective randomized study.

Comparison of unrelated cord blood transplantation and HLA-identical sibling peripheral blood stem cell transplantation for the treatment of adult hematological malignancies

目的比较单份清髓非血缘脐血移植（UCBT）与HLA相合同胞外周血干细胞移植（PBSCT）治疗成人恶性血液病的疗效。方法自2011年4月1日至2015年12月31日，共81例单份清髓UCBT与57例HLA相合同胞PBSCT患者入组进行比较。所有患者均采用清髓性预处理方案，环孢素A联合霉酚酸酯预防移植物抗宿主病（GVHD）。结果移植后42 d（+42 d）UCBT组中性粒细胞累积植入率为95.0%（95%CI 87.0%~98.1%），同胞PBSCT组为100%（P=0.863）。+100 d UCBT组血小板累积植入率低于同胞PBSCT组[87.3%（95%CI 76.8%~93.1%）对98.2%（95%CI 87.3%~99.7%），P=0.005]。+100 d UCBT组Ⅱ~Ⅳ度急性GVHD、Ⅲ/Ⅳ度急性GVHD的累积发生率分别为18.2%（95%CI 9.1%~26.4%）、10.4%（95%CI 3.3%~16.9%），同胞PBSCT组分别为8.9%（95%CI 1.1%~16.1%）、7.1%（95%CI 1.4%~13.7%），差异均无统计学意义（P=0.142，P=0.521）。UCBT组3年慢性GVHD、广泛型慢性GVHD累积发生率均低于同胞PBSCT组[14.9%（95%CI 5.2%~23.5%）对35.2%（95%CI 19.4%~47.8%），P=0.008；11.2%（95%CI 2.9%~18.7%）对31.4%（95%CI 16.2%~43.9%），P=0.009]。UCBT组、同胞PBSCT组3年移植相关死亡率（TRM）差异无统计学意义[30.1%（95%CI 19.2%~41.7%）对23.2%（95%CI 13.1%~35.0%），P=0.464]。UCBT组3年疾病复发率低于同胞PBSCT组[12.9%（95%CI 6.6%~21.5%）对24.3%（95%CI 13.5%~36.8%），P=0.039]。UCBT、同胞PBSCT组3年总生存率、无病生存率差异均无统计学意义[58.6%（95%CI 45.4%~69.7%）对54.8%（95%CI 39.9%~67.4%），P=0.634；57.0%（95%CI 44.0%~68.0%）对52.4%（95%CI 38.2%~64.9%），P=0.563]。UCBT组3年无GVHD及复发生存（GRFS）率高于同胞PBSCT组[55.7%（95%CI 44.1%~65.8%）对42.9%（95%CI 29.8%~55.3%），P=0.047]。结论对于成人恶性血液病，UCBT与HLA相合同胞PBSCT具有相似的急性GVHD发生率、TRM、总生存率和无病生存率，但UCBT组具有较低的慢性GVHD发生率及疾病复发率。

Allogeneic Stem Cell Transplantation for Relapsed/Refractory B Cell Lymphomas: Results of a Multicenter Phase II Prospective Trial including Rituximab in the Reduced-Intensity Conditioning Regimen

The treatment of patients with refractory/relapsed B cell non-Hodgkin lymphoma (NHL) is evolving because of the availability of novel drugs. Allogeneic stem cell transplantation (alloSCT) can be curative, but its morbidity and mortality remain a matter of concern. We conducted a multicenter prospective phase II trial to evaluate the benefit of including only 1 dose of rituximab in the conditioning regimen before alloSCT. The primary endpoint was progression-free survival. The study enrolled 121 patients with relapsed/refractory B cell lymphomas. The conditioning regimen consisted of thiotepa, cyclophosphamide, fludarabine, and rituximab (500 mg/m2). Rabbit antithymocyte globulin was administered only in case of unrelated donors. Sixty-seven (55%) and 54 (45%) patients received grafts from related and unrelated donors, respectively. The crude cumulative incidence (CCI) of nonrelapse mortality (NRM) was 21% at 3 years. The CCIs of chronic graft-verus-host disease (GVHD) at 3 years were 54% and 31% in recipients of matched sibling and unrelated grafts, respectively. At a median follow-up of 41 months, the estimated 3-year progression-free and overall survival were 50% and 61%, respectively. Long-term outcome was also evaluated with the composite endpoint of GVHD-free and relapse-free survival (GRFS). This is the first work evaluating the GRFS in a prospective trial of lymphoma patients: the 1-year and 3-year GRFS were 40% and 34%, respectively. AlloSCT can cure a fraction of patients with rather low NRM and an encouraging PFS and GRFS.

Association Between Multiple Mismatches at the HLA-DPB1 and DRB3/4/5 Genes and Adverse Outcomes in HLA-a, -B, -C, -DRB1 and -DQB1 Identical Hematopoietic Stem Cell Transplantation: A Study on Behalf of the Francophone Society of Stem Cell Transplantation and Cellular Therapy (SFGM-TC) and the Francophone Society for Histocompatibility and Immunogenetics (SFHI)

Background: Matching for all alleles of the HLA-A, -B, -C, and -DRB1 loci (8/8 match) is associated with the highest overall survival (OS) rates after unrelated donor (URD) hematopoietic stem cell transplantation (HSCT). In Europe, patients (pts) are also matched at the HLA-DQB1 loci (10/10 match) with no overall evidence of improved OS. HLA-DPB1 mismatching has been associated with a higher risk of acute graft-versus-host disease (aGvHD) and a decreased risk of relapse. A detrimental role of additional HLA-DQB1, HLA-DPB1 and HLA-DRB3/4/5 mismatches (MM) has been recently identified on OS but only in 7/8 HLA-A, -B, -C, and -DRB1 loci URDs HSCT. We investigated the impact of HLA-DPB1 and HLA-DRB3/4/5 MM on outcomes in a large cohort of 10/10 matched URD HSCTs.Patients and methods: 2,393 pts who received an initial HSCT from a 10/10 matched URD in 35 French centers were included between January 2000 and October 2012. Informed consent was obtained in accordance with the Declaration of Helsinki. High-resolution typing was performed for HLA-A, -B, -C, -DRB1, -DQB1, -DPB1 and -DRB3/4/5 loci for all donor/recipient pairs. Clinical data were obtained through ProMISe (Project Manager Internet Server), an internet-based system shared by all French transplantation centers. Impact of HLA-DRB3/4/5 and -DPB1 MM was quantitatively and qualitatively evaluated. For quantitative evaluation, patients were classified into 5 different groups according to their global matching level for the 7 considered loci (14/14, 13/14, 12/14, 11/14, 10/14). For qualitative evaluation, MM type and directionality (GvH and host versus graft (HvG) directions) were evaluated. HLA-DPB1 MM were classified as permissive or non-permissive (K Fleischhauer, Lancet Oncol. 2012). The primary composite endpoint for the analysis was GvHD-free and relapse-free survival (GRFS). We defined early GRFS as being alive at 3 months after HSCT with no previous grade III-IV aGvHD and no relapse and late GRFS as being alive >3 months with no previous grade III-IV aGvH, no relapse and no moderate or severe chronic GvHD (cGvHD). Late GRFS was evaluated at months 6, 12, 24 and 36 after HSCT. Acute GvHD, cGvHD, relapse and OS were also studied. Models were adjusted for HSCT period, disease risk, age, sex matching, stem cell source, and conditioning regimen.Results: Table 1showspopulation characteristics and distribution of cumulative MM. The median follow-up was 59 months. Compared to 14/14 pairs, quantitative evaluation showed a significantly lower early GRFS for pts who received a 10-11/14 (Hazard Ratio HR 2.0, 95% CI 1.4 to 2.9, p=0.0003) or a 12/14 URD HSCT (HR 1.4, 95% CI 1.1 to 1.8, p=0.01). This was related to a significantly increased risk of grade III-IV aGVHD associated with 10-11/14 (HR 2.3, 95% CI 1.5 to 3.7, p=0.0004) and 12/14 pairs (HR 1.7, 95% CI 1.2 to 2.4, p=0.003). 10-11/14 pairs were also associated with a higher risk of death at 3 months (HR 2, 95% CI 1.1 to 3.6, p=0.024). Qualitatively, in pts matched for HLA-DRB3/4/5 but MM for HLA-DPB1 (n=1846, 77.1%), 2 HLA-DPB1 MM and non-permissive HLA-DPB1 MM were associated with a lower early GRFS (HR 1.4, 95% CI 1.1 to 1.9, p=0.01 and HR 1.3, 95% CI 1.0 to 1.7, p=0.02 respectively) due to an increased risk of aGvHD (HR 1.7, 95% CI 1.2 to 2.5, p=0.002 and HR 1.50, 95% CI 1.08 to 2.08, p= 0.017 respectively). Outcomes were not influenced by either GvHD or HvG mismatch directions. Late GRFS analyses once adjusted were not significantly different according to MM numbers, type and directions. Only 19 pairs (0.8%) were DPB1 matched and DRB3/4/5 mismatched (high linkage disequilibrium between DRB3/4/5 and DRB1); HLA-DRB3/4/5 MM could thus not be qualitatively analyzed.Conclusion: MultipleHLA-DPB1 and HLA-DRB3/4/5 MM have an early impact after 10/10 matched URDs HSCT. The best outcomes are seen in 13 and 14/14 pairs. Early GRFS is significantly impacted by 10-11/14, 12/14, 2 DPB1 MM as well as non-permissive HLA-DPB1 MM URD HSCT which is related to an increased risk of grade III-IV aGvHD. There is a significantly increased risk of mortality for 10-11/14 pairs at 3 months. Prospective evaluation of matching for HLA-DPB1 and HLA-DRB3/4/5 is warranted to reduce early post-HSCT toxicity in donor-recipient 10/10 matched pairs. [Display omitted] DisclosuresMichallet:Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Astellas Pharma: Consultancy, Honoraria; MSD: Consultancy, Honoraria; Genzyme: Consultancy, Honoraria. Peffault De Latour:Pfizer: Consultancy, Honoraria, Research Funding; Alexion: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Amgen: Research Funding.