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Haploidentical hematopoietic stem cell transplantation (Haplo-SCT) and matched unrelated donor transplantation (MUD-SCT) are two important options when a matched sibling donor (MSD) is unavailable. Several studies comparing Haplo-SCT and MUD-SCT have reported inconsistent clinical outcomes. Therefore, it is necessary to synthesize the existing evidence regarding outcomes of stem cell transplantations comparing Haplo-SCT with MUD-SCT.We searched for titles of articles in MEDLINE (PubMed), Cochrane library, EMBASE database that compared transplantation with Haplo-SCT versus MUD-SCT. To compare clinical outcomes between Haplo-SCT and MUD-SCT, we performed a meta-analysis of 17 studies and reported the pooled odd ratios (OR) of 6 endpoints including overall survival (OS), progression free survival (PFS), non-relapse mortality (NRM), relapse rate (RR), acute graft-versus-host disease (aGVHD) and chronic graft- versus-host disease (cGVHD).We found that Haplo-SCT was associated with a comparable OS (pooled OR of 0.99, 95% Confidence Interval (CI) 0.86-1.14), PFS (OR 1.00, 95% CI 0.88-1.15), NRM (OR 0.83, 95% CI 0.65-1.04) and RR (OR 1.08, 95% CI 0.95-1.22) compared to MUD-SCT. We also found a significantly decreased risk of aGVHD (OR 0.74, 95% CI 0.62-0.88) and cGVHD (OR 0.50, 95% CI 0.38-0.66) in Haplo-SCT group.Results of this meta-analysis demonstrates that Haplo-SCT achieves comparable clinical outcomes compared to MUD-SCT in terms of OS, PFS, TRM and RR, but is better than MUD-SCT in terms of decreased aGVHD and cGVHD risk. Haplo-SCT is a valid option for patient needing urgent transplantation.

PURPOSE: To characterize donor search and selection practices, the National Marrow Donor Program (NMDP) Histocompatibility Advisory Group developed a survey of allogeneic hematopoietic cell transplant (HCT) physicians and search coordinators. Objectives were to describe search practices, understand practices surrounding urgent time to HCT, and characterize strategies used when identifying a matched unrelated donor (MUD) is unlikely. METHODS: Participants included United States physician members of the American Society for Transplantation and Cellular Therapy (ASTCT) and donor search coordinators within the NMDP network. The web-based survey was conducted February to May 2018. RESULTS: A total of 317/858 physicians (37%) and 225/327 coordinators (69%) responded, of which 263 and 194 respectively were eligible and were included in the analysis. Most centers, 142 (95%) were represented; 108 (72%) had at least one physician and 128 (85%) had at least one coordinator respondent. Most (68% physicians, 61% coordinators) indicated donor selection decisions were made by individual physicians. Urgent time to HCT was most commonly (90 and 87%, of physicians and coordinators, respectively) defined as HCT within 4–6 weeks of search nitiation. Higher HCT urgency was associated with a higher disease risk index. For urgent cases with low probability of an 8/8 MUD, 75 and 80% of physicians and coordinators endorsed short (1–2 weeks) unrelated donor search before proceeding to an alternative donor source. NMDP-provided solutions to expedite donor identification were strongly endorsed. CONCLUSIONS: This survey clarified current donor selection practices in the United States and defined urgent time to HCT. These data provide insight to NMDP on potential solutions to support the path to transplant, such as highlighting futile searches and providing alternative donor options at the time of search initiation.

This study compares the outcomes before and after reducing the ATG dose from 4.5 to 2 mg/kg, in a combination of PTCy and CsA for GVHD prevention, in 250 patients treated with HLA matched RIC PB-alloHCT (70% received 4.5 mg/kg and 30% received 2 mg/kg). The incidences of grade II-IV and III-IV aGVHD at day +100, and moderate/severe cGVHD at 1-year were 12.6% vs. 20% (

Availability of 8/8 HLA-allele matched unrelated donors (URDs) is a barrier for ethnic and racial minorities. We prospectively evaluated receipt of 8/8 HLA-allele matched URD or either 7/8 URD or cord blood (CB) transplants by patient ancestry from 2005 to 2017. Matched URDs were given priority if they were available. Of 1312 patients, 723 (55%) received 8/8 URD, 219 (17%) 7/8 URD, 319 (24%) CB, and 51 (4%) had no 7/8 or 8/8 URD or CB graft. Europeans were more likely to receive an 8/8 URD transplant than non-Europeans (67% vs 33%) and less likely to have no URD or CB graft (1% vs 9%). Southern Europeans received 8/8 URD transplants (41%) at rates similar to those of Asians (34%) and white Hispanics (35%); Africans were the least likely (18%) to undergo 8/8 URD transplantation. CB and 7/8 URDs extended transplant access to all groups. In 742 recent patients, marked racial disparity in 8/8 URD access between groups observed in earlier years persisted with only a modest increase in the percentage of 8/8 URD transplants. Of 78 recent African patients, 46% received a CB transplant and 14% had no 7/8 or 8/8 URD or CB graft. Increasing registry size has not resolved the racial disparity in URD access, which emphasizes the importance of alternative graft sources.

Introduction: Currently, more than 10,000 matched unrelated donor transplants (MUDT) are performed annually worldwide. India has recorded a significant increase in the number of hematopoietic progenitor cell transplantation (HPCT) centers reporting transplants. The number of HPCTs increases by approximately 10% every year, with 1878 transplants reported by Indian stem cell transplant registries in 2016. However, published outcome data of MUDT in India are scant, with reports limited to autologous and allogenic matched unrelated transplants, which motivated us to present our MUDT data. Aims and objective: To review the operations, and more importantly, the patient outcome data of a new registry in India. Materials and methods: We accessed an Indian HLA donor database with high-resolution HLA typing results of 7682 (until 31st July 2018) volunteer HLA donors. The typing results were uploaded to proprietary software. The search result was considered a “match” when a 10/10 potential HLA match was found. Patients who were found to be alive through mail communication and did not exhibit signs and symptoms of disease were considered to have disease-free survival (DFS). Results: During the six years of operations of the database, 1165 searches resulted in 68 10/10 matches from the registry. Of these, 11 were MUD HPCT records. At a minimum follow-up of almost 11 months, seven recipients continue to exhibit DFS. Conclusions: The patient DFS data prove that even a small registry with slightly more than 7000 donors can yield reasonably good patient outcomes. Keywords: MUD, HPCT, Transplant, Disease-free survival (DFS)

Natural killer (NK) cells are the first population to recover after allogeneic hematopoietic stem cell transplantation. Since the report in 2002 by L. Rugerri et al. showing the effectiveness of NK cell alloreactivity in haploidentical stem cell transplantation, a lot of conflicting studies have appeared about the role of NK alloreactivity in haploidentical and matched unrelated donor transplantations. Current studies demonstrate that the beneficial effects of donor NK alloreactivity are dependent on the transplant protocol – conditioning regimen, graft processing procedure and graft-versus-host disease.

Background: Cryopreservation of PBSC for allogenic hematopoietic stem cell transplantation (allo-HSCT) was implemented due to the current Coronavirus 2019 pandemic. The impact of match unrelated donor (MUD) graft freezing on the outcome of allo-HSCT in terms of hematological recovery, graft versus host disease (GVHD), and survival are still controversial. Methods: In this study, we compared graft composition, clinical characteristics, and outcome of 31 allo-HSCT from MUD cryopreserved PBSC (Cryo Group) with 23 matched-pair allo-HSCT from fresh MUD PBSC (Fresh Group) performed in our center between January 2020 and July 2021. Results: No significant differences were recognized in clinical characteristics of patients, donors, and transplants between the Cryo and Fresh groups except for a better prognostic comorbidity index (HCT-CI) of the Cryo group. In the Cryo Group, the median time from apheresis to cryopreservation was 46.0 h (range 23.8–53.5), while the median time from cells collection and reinfusion was 13.9 days (range 5.8–28.1). In the Fresh Group, median time from apheresis to reinfusion was 35.6 h (range 21.4–51.2). The number of viable (7-AAD negative) CD34+ cells per kg patient infused was significantly lower in the Cryo Group (5.2 ± 1.9 × 106/kg vs. 7.0 ± 1.3 × 106/kg; p < 0.001). Indeed, there was a 36% (11–70) median loss of viable CD34+/kg cells after freezing. All patients engrafted: median time to neutrophil engraftment (>0.5 × 109/L) was 13.5 days (range 12–15) for Cryo Group and 14 days (range 13–16) days for Fresh Group (p = 0.522), while the median time to platelet engraftment (>20 × 109/L) was, respectively, 14 (range 12–18) and 15 (range 12–17) days (p = 0.904). The incidence of grade ≥ 2 acute GVHD was similar in the two groups (56.5% Cryo Group vs. 60.0% Fresh Group; p = 0.832) and no differences in terms of OS (p = 0.090), PFS (p = 0.200) and TRM (p = 0.970) were observed between the Cryo and Fresh groups. Conclusions: In our series, no differences between the Cryo and Fresh groups were found in engraftment, grade ≥ 2 acute GVHD incidence, OS, PFS, and TRM despite a lower CD34+ infused dose in the Cryo Group. Frozen PBSCs could be considered a safe option also for allo-HSCT from MUD but a higher amount of PBSC should be collected to warrant an adequate viable CD34+ post-thawing.

PURPOSE Donor selection practices for matched unrelated donor (MUD) hematopoietic cell transplantation (HCT) vary, and the impact of optimizing donor selection in a patient-specific way using modern machine learning (ML) models has not been studied. METHODS We trained a Bayesian ML model in 10,318 patients who underwent MUD HCT from 1999 to 2014 to provide patient- and donor-specific predictions of clinically severe (grade 3 or 4) acute graft-versus-host disease or death by day 180. The model was validated in 3,501 patients from 2015 to 2016 with archived records of potential donors at search. Donor selection optimizing predicted outcomes was implemented over either an unlimited donor pool or the donors in the search archives. Posterior mean differences in outcomes from optimal donor selection versus actual practice were summarized per patient and across the population with 95% intervals. RESULTS Event rates were 33% (training) and 37% (validation). Among donor features, only age affected outcomes, with the effect consistent regardless of patient features. The median (interquartile range) difference in age between the youngest donor at search and the selected donor was 6 (1-10) years, whereas the number of donors per patient younger than the selected donor was 6 (1-36). Fourteen percent of the validation data set had an approximate 5% absolute reduction in event rates from selecting the youngest donor at search versus the actual donor used, leading to an absolute population reduction of 1% (95% interval, 0 to 3). CONCLUSION We confirmed the singular importance of selecting the youngest available MUD, irrespective of patient features, identified potential for improved HCT outcomes by selecting a younger MUD, and demonstrated use of novel ML models transferable to optimize other complex treatment decisions in a patient-specific way.

Standardization of histocompatibility tests for allogeneic hematopoietic cell transplants, harmonization of information transmitted to clinicians are part of quality improvement and optimization of human and economic resources. New HLA typing technologies provide high-resolution information within a reasonable time frame. Knowledge of high-resolution HLA typing for the patient and their relatives is essential for a better interpretation of compatibilities. HLA-DPB1 typing must be considered in transplant field regardless of the donor type. The benefits of using search and match programs are considerable. It saves time and reduces additional typing costs by providing rapid information about the likelihood to identify a matched unrelated donor. A backup therapy considering alternative cell sources or treatment can therefore be quickly implemented. The importance of knowledge and consideration of patient immunization for donor choice was explored in previous workshops of the SFGM-TC (2018 and 2019). The published recommendations remain applicable. The routine follow-up protocol and in case of desensitization will be detailed here. This harmonization must be accompanied by the standardization of information to be returned to the clinician regarding the donor finding possibilities for the patient. This will guarantee a similar quality level in every center.

International audience; The association of Cyclosporine A (CsA) and mycophenolate mofetil (MMF) has increased in the setting of reduced intensity conditioning (RIC). Nevertheless, the use of CsA or CsA+MMF has not been reported in a large and uniform cohort. We analyzed 497 patients with acute myeloid leukemia in complete remission (CR) who underwent matched unrelated donor (MUD) hematopoietic stem cell transplantation (HSCT). All patients received a fludarabine busulfan RIC regimen and anti-thymocyte globulin (ATG) with either CsA alone or in combination with MMF. The cumulative incidence (CI) of grade II-IV acute GvHD was 27% (95% CI 21-33%) for CsA and 33% (95% CI 27-38%) for CsA+MMF (p = 0.25). The 2-year CI of chronic GvHD was 38% (95% CI 31-45%) and 33% (95% CI 28-39%) for the CsA and the CsA+MMF group, respectively (p = 0.26). On multivariate analysis, no statistically significant differences with respect to relapse incidence (RI), non-relapse mortality (NRM), leukemia-free survival (LFS), overall survival (OS), acute and chronic GvHD were found between the two groups, also when conducting a subgroup analysis in peripheral blood stem cells (PBSC) recipients. Our results support the importance of randomized trial to identify patients who could benefit from the addition of MMF in MUD HSCT.

We compared transplant outcomes of 708 acute myeloid leukemia (AML) patients receiving haploidentical allogeneic hematopoietic-cell transplantation using thiotepa/busulfan/fludarabine (TBF) conditioning with posttransplant cyclophosphamide (ptCy), to 2083 patients receiving matched unrelated donor (MUD) transplantation using fludarabine/busulfan (FB) conditioning and in vivo T-cell depletion. For intermediate cytogenetic risk AML transplanted in first complete remission (CR1), multivariate analysis revealed that haplo-TBF significantly increased nonrelapse mortality (NRM) (HR 2.1; p = 0.0006) but did not affect relapse incidence (RI), leukemia-free survival (LFS), overall survival (OS), or graft-versus-host disease-free, relapse-free survival (GRFS). For high cytogenetic risk AML transplanted in CR1, haplo-TBF significantly increased NRM (HR = 2.7; p = 0.02), decreased RI (HR = 0.45; p = 0.03) but had no influence on LFS, OS, or GRFS. For AML transplanted in CR2, haplo-TBF significantly increased NRM (HR = 2.36; p = 0.008), decreased RI (HR = 0.38; p = 0.005), but had no influence on LFS, OS, or GRFS. Finally, for AML patients transplanted with active disease, haplo-TBF had no influence on transplant outcomes. In conclusion, compared to MUD-FB, haplo-TBF increased NRM, reduced RI in high-risk AML in CR, resulting in similar LFS, OS, and GRFS. These results comparing two different approaches support the use of a haploidentical family donor for high-risk AML patients lacking a matched sibling donor.

Aplastic anemia is a hematological disease with deadly complications related to pancytopenia if not treated in a timely manner. First-line treatment consists of immunosuppressive therapy or matched sibling donor (MSD) hematopoietic stem cell transplant. Step up treatment involves a matched unrelated donor (MUD) hematopoietic stem cell transplant (HSCT) alongside immunosuppressant conditioning. However, recent research suggests that there is improved success of MUD HSCT for severe aplastic anemia compared to immunosuppressive therapy. We present a case of an 18-year-old who was diagnosed with severe aplastic anemia who received numerous immunosuppressive therapy regimens prior to obtaining a MUD HSCT. Over a year after bone marrow transplant, the patient is doing well with no signs of rejection. This case creates an argument for the use of upfront MUD HSCT as a curative treatment for acquired aplastic anemia rather than initial treatment with immunosuppressive agents.

The present study describes a patient aged 70 with very high-risk AML who successfully received a nonmyeloablative matched unrelated donor allograft shortly following SARS-CoV-2 infection, which manifested with mild cough, interstitial abnormalities on chest CT, and pancytopenia with profound bone marrow biopsy histological alterations. In parallel, our study provides bone marrow biopsy data in a series of contemporary patients with serious haematological diseases who had a bone marrow biopsy performed within two weeks of PCR confirmation of SARS-CoV-2 infection. This study is notable because there are no published data describing the bone marrow biopsy changes observed in patients with haematological malignancies and SARS-CoV-2 infection. Finally, it is suggested that nonmyeloablative hematopoietic stem cell transplantation for very high-risk haematological malignancies can be successfully performed following recovery from SARS-CoV-2 infection.

Hematopoietic stem cell transplant (HSCT) is currently the only curative option for thalassemia major (TM) and sickle cell disease (SCD). We report our experience of using pretransplant immune suppression (PTIS), augmented Johns Hopkins conditioning, and posttransplant cyclophosphamide (PTCy) as graft-versus-host disease (GvHD) prophylaxis for matched unrelated donor (MUD) transplant in TM/SCD. At a median follow-up of 307.5 days (range 251-395), all patients (three TM, one SCD) are alive and disease free. MUD HSCT with PTIS, augmented Johns Hopkins conditioning, and PTCy as GvHD prophylaxis is a promising way of treating patients with hemoglobinopathies with low regimen-related toxicity (RRT), no risk of graft failure (GF) and minimal GvHD rates.

Minimal residual disease (MRD) in acute myeloid leukemia (AML) is a complex, multi-modality assessment and much as its clinical implications at different points are extensively studied, it remains even now a challenging area. It is the disease biology that governs the modality of MRD assessment; in patients harboring specific molecular targets, high sensitivity techniques can be applied. In AML patients undergoing allogenic hematopoietic stem cell transplantation (alloHSCT), relapse in considered as leading cause for treatment failure. In post-transplant setting, regular MRD status assessment enables to identify patients at risk of impending relapse when early therapeutic intervention may be beneficent. We analyzed data of AML patients who underwent matched unrelated donor (MUD) HSCT since the introduction of this procedure in the Republic of North Macedonia. Chimeric fusion transcripts were identified in three patients; two of them positive for RUNX-RUNX1T1 transcript and one for CBFB-MYH11. One patient harbored mutation in the transcription factor CCAAT/enhancer binding protein α (CEBPA). Post-transplant MRD kinetics was measured by quantitative polymerase chain or multiplex fluorescent-PCR every three months after the transplantation during the first two years after the transplant. MRD negativity was achieved in three patients by the sixth month of HSCT, who were pre-transplant MRD positive. They sustained hematological and molecular remission for 19, 9 and 7 months, respectively. The forth patient died due to transplant-related complication. Our experience suggests, when molecularly-defined AML patients undergo HSCT, regular MRD monitoring helps predict impending relapse and direct future treatment strategies.

BackgroundAcute kidney injury (AKI) remains a frequent complication in children undergoing hematopoietic stem cell transplantation (HSCT) and an independent risk factor of the patient’s survival and a prognostic factor of progression to chronic kidney disease (CKD). However, the causes of these complications are diverse, usually overlapping, and less well understood.MethodsThis retrospective analysis was performed in 43 patients (28 boys, 15 girls; median age, 5.5 years) undergoing HSCT between April 2006 and March 2019. The main outcome was the development of AKI defined according to the Pediatric Risk, Injury, Failure, Loss, End-stage Renal Disease (pRIFLE) criteria as ≥ 25% decrease in estimated creatinine clearance. The secondary outcome was the development of CKD after a 2-year follow-up.ResultsAKI developed in 21 patients (49%) within 100 days after HSCT. After adjusting for possible confounders, posttransplant AKI was associated with matched unrelated donor (MUD) (HR, 6.26;P = 0.042), but not total body irradiation (TBI). Of 37 patients who were able to follow-up for 2 years, 7 patients died, but none had reached CKD during the 2 years after transplantation.ConclusionsPosttransplant AKI was strongly associated with HSCT from MUD. Although the incidence of AKI was high in our cohort, that of posttransplant CKD was lower than reported previously in adults. TBI dose reduced, GVHD minimized, and infection prevented are required to avoid late renal dysfunction after HSCT in children since their combinations may contribute to the occurrence of AKI.

International audience; Full text linksfull-text provider logoActionsFavoritesSharePage navigation Title & authors Abstract Conflict of interest statement Figures References Related information LinkOut - more resourcesJ Hematol Oncol. 2020 Jul 3;13(1):87.doi: 10.1186/s13045-020-00923-0.Post-transplant cyclophosphamide versus antithymocyte globulin in patients with acute myeloid leukemia in first complete remission undergoing allogeneic stem cell transplantation from 10/10 HLA-matched unrelated donorsEolia Brissot 1 2 , Myriam Labopin 3 , Ian Moiseev 4 , J J Cornelissen 5 , Ellen Meijer 6 , Gwendolyn Van Gorkom 7 , Montserrat Rovira 8 , Fabio Ciceri 9 10 , Laimonas Griskevicius 11 , Didier Blaise 12 , Edouard Forcade 13 , Martin Mistrik 14 , Stephan Mielke 15 , Claude Eric Bulabois 16 , Riitta Niittyvuopio 17 , Eric Deconinck 18 , Annalisa Ruggeri 9 10 , Jaime Sanz 19 20 , Alexandros Spyridonidis 21 , Bipin Savani 22 , Sebastian Giebel 23 , Arnon Nagler 24 , Mohamad Mohty 25 26Affiliations PMID: 32620146 PMCID: PMC7333262 DOI: 10.1186/s13045-020-00923-0 Free PMC articleAbstractBackground: Graft-versus-host disease (GVHD) remains a major contributor to mortality and morbidity after allogeneic stem-cell transplantation (allo-HSCT). The updated recommendations suggest that rabbit antithymocyte globulin or anti-T-lymphocyte globulin (ATG) should be used for GVHD prophylaxis in patients undergoing matched-unrelated donor (MUD) allo-HSCT. More recently, using post-transplant cyclophosphamide (PTCY) in the haploidentical setting has resulted in low incidences of both acute (aGVHD) and chronic GVHD (cGVHD). Therefore, the aim of our study was to compare GVHD prophylaxis using either PTCY or ATG in patients with acute myeloid leukemia (AML) who underwent allo-HSCT in first remission (CR1) from a 10/10 HLA-MUD.Methods: Overall, 174 and 1452 patients from the EBMT registry receiving PTCY and ATG were included. Cumulative incidence of aGVHD and cGVHD, leukemia-free survival, overall survival, non-relapse mortality, cumulative incidence of relapse, and refined GVHD-free, relapse-free survival were compared between the 2 groups. Propensity score matching was also performed in order to confirm the results of the main analysis RESULTS: No statistical difference between the PTCY and ATG groups was observed for the incidence of grade II-IV aGVHD. The same held true for the incidence of cGVHD and for extensive cGVHD. In univariate and multivariate analyses, no statistical differences were observed for all other transplant outcomes. These results were also confirmed using matched-pair analysis.Conclusion: These results highlight that, in the10/10 HLA-MUD setting, the use of PTCY for GVHD prophylaxis may provide similar outcomes to those obtained with ATG in patients with AML in CR1.

Overcoming graft-versus-host disease (GvHD) without increasing relapse and severe infections is a major challenge after allogeneic hematopoietic stem-cell transplantation (HSCT). ATIR101 is a haploidentical, naïve cell-enriched T-cell product, depleted of recipient-alloreactive T cells to minimize the risk of GvHD and provide graft-versus-infection and -leukemia activity. Safety and efficacy of ATIR101 administered after T-cell-depleted haploidentical HSCT (TCD-haplo + ATIR101) without posttransplant immunosuppressors were evaluated in a Phase 2, multicenter study of 23 patients with acute leukemia and compared with an observational cohort undergoing TCD-haplo alone (n = 35), matched unrelated donor (MUD; n = 64), mismatched unrelated donor (MMUD; n = 37), and umbilical cord blood (UCB; n = 22) HSCT. The primary endpoint, 6-month non-relapse mortality (NRM), was 13% with TCD-haplo + ATIR101. One year post HSCT, TCD-haplo + ATIR101 resulted in lower NRM versus TCD-haplo alone (P = 0.008). GvHD-free, relapse-free survival (GRFS) was higher with TCD-haplo + ATIR101 versus MMUD and UCB (both P < 0.03; 1-year rates: 56.5%, 27.0%, and 22.7%, respectively) and was not statistically different from MUD (1 year: 40.6%). ATIR101 grafts with high third-party reactivity were associated with fewer clinically relevant viral infections. Results suggest that haploidentical, selective donor-cell depletion may eliminate requirements for posttransplant immunosuppressors without increasing GvHD risk, with similar GRFS to MUD. Following these results, a randomized Phase 3 trial versus posttransplant cyclophosphamide had been initiated., SCOPUS: ar.j, info:eu-repo/semantics/published

We assessed differences in presentation and response to therapy in 394 consecutive patients who developed acute or chronic graft-versus-host disease (GVHD) after receiving their first allogeneic transplantation (HSCT) from a 10/10 HLA allele-matched unrelated donor (MUD; n = 179) using calcineurin inhibitors or a T cell-replete haploidentical donor (haplo; n = 215) and post-transplantation cyclophosphamide at our center between 2005 and 2017. The median duration of follow-up for survivors was 52.5 months. The cumulative incidences for grade II-IV and grade III-IV acute GVHD at day 180 post HCT were similar, at 39% and 14%, respectively, for haplo-HSCT compared with 50% and 16% for MUD HSCT (P not significant). Haplo-HSCT recipients had a lower cumulative incidence of moderate to severe chronic GVHD, at 22% (severe, 19%), compared with 31% (severe, 29%) for MUD HSCT recipients (P = .026). The time to onset of moderate to severe chronic GVHD was faster for haplo-HSCT recipients (213 days versus 280 days; P = .011). Among patients with grade II-IV acute GVHD, there was no significant between-group difference in organ involvement, with skin the most affected (75% for haplo-HSCT versus 70% for MUD HSCT), followed by the gastrointestinal tract (71% versus 69%) and liver (14% versus 17% MUD). For chronic GVHD, haplo-HSCT recipients had less involvement of the eyes (46% versus 75% for MUD; P.001) and of the joints/fascia (12% versus 36%; P = .001). Also for cGVHD patients, haplo-HSCT recipients and MUD HSCT recipients had similar all-cause mortality (22% versus 18%; P = .89), but the former were more likely to be off immunosuppression at 2 years post-HCT (63% versus 43%; P = .03) compared with MUD.

Anti-thymocyte globulin (ATG) has been associated with decreased rates graft versus host disease (GVHD) but with a potential risk of increasing risk of infection and relapse. We retrospectively studied the impact of single dose low dose (2.5 mg/kg) ATG in patients undergoing allogenic hematopoietic cell transplantation (HCT) from 8/8 matched unrelated donors (MUD). Of the total 209 patients identified, 129 received ATG. At baseline, the ATG group had more intermediate and high disease risk index (DRI) (64.6% vs. 54.3%) (28.3% vs. 23.7%)

Rationale: Very severe aplastic anemia (vSAA) with active infections is always fatal. Adequate infection control before hematopoietic stem cell transplantation is recommended. Patient concerns: A 38-year-old woman with vSAA suffered from acute perforated appendicitis and invasive pulmonary fungal infection, and she failed to respond to intense antimicrobial therapies. Diagnosis: She was diagnosed with refractory vSAA with stubborn acute perforated appendicitis and invasive pulmonary fungal infection. Interventions: We successfully completed an emergent reduced intensity conditioning-matched unrelated donor (MUD)-peripheral blood stem cell transplantation (PBSCT) as a salvage therapy in the presence of active infections. The conditioning regimens consisted of reduced cyclophosphamide 30 mg/kg/day from day-5 to day-3, fludarabine 30 mg/m2/day from day-5 to day-3 and porcine-antilymphocyte immunoglobulin 15 mg/kg/day from day-4 to day-2 without total body irradiation. Cyclosporin A, mycophenolate mofetil and short-term methotrexate were administered as graft-versus-host disease (GVHD) prophylaxis. Neutrophils and platelets were engrafted on day+15 and day+21. Appendiceal abscess and severe pneumonia developed after neutrophil engraftment, which were successfully managed with intense antimicrobial therapy and surgical intervention. Outcomes: Only limited cutaneous chronic GVHD was observed 5 months after transplantation. The patient still lives in a good quality of life 2 years after transplantation. Lessons: Active infections may be no longer a contraindication to hematopoietic stem cell transplantation for some patients with vSAA.

Following allogeneic blood and marrow transplantation (BMT), graft-versus-host disease (GvHD) continues to represent a significant cause of treatment failure, despite the routine use of conventional, mainly calcineurin inhibitor-based prophylaxis. Recently, post-transplant cyclophosphamide (PTCy) has emerged as a safe and efficacious alternative. First, omitting the need for ex vivo T-cell depletion in the setting of haploidentical transplantation, growing evidence supports PTCy role in GvHD prevention in matched-related and matched-unrelated transplants. Through improved understanding of GvHD pathophysiology and advancements in drug development, PTCy emerges as a unique opportunity to design calcineurin inhibitor-free strategies by integrating agents that target different stages of GvHD development.

We compared outcomes of 1461 adult patients with acute lymphoblastic leukemia (ALL) receiving hematopoietic cell transplantation (HCT) from a haploidentical (n = 487) or matched unrelated donor (MUD; n = 974) between January 2005 and June 2018. Graft-versus-host disease (GVHD) prophylaxis was posttransplant cyclophosphamide (PTCy), calcineurin inhibitor (CNI), and mycophenolate mofetil (MMF) for haploidentical, and CNI with MMF or methotrexate with/without antithymoglobulin for MUDs. Haploidentical recipients were matched (1:2 ratio) with MUD controls for sex, conditioning intensity, disease stage, Philadelphia-chromosome status, and cytogenetic risk. In the myeloablative setting, day +28 neutrophil recovery was similar between haploidentical (87%) and MUD (88%) (P = .11). Corresponding rates after reduced-intensity conditioning (RIC) were 84% and 88% (P = .47). The 3-month incidence of grade II-IV acute GVHD (aGVHD) and 3-year chronic GVHD (cGVHD) was similar after haploidentical compared with MUD: myeloablative conditioning, 33% vs 34% (P = .46) for aGVHD and 29% vs 31% for cGVHD (P = .58); RIC, 31% vs 30% (P = .06) for aGVHD and 24% vs 29% for cGVHD (P = .86). Among patients receiving myeloablative regimens, 3-year probabilities of overall survival were 44% and 51% with haploidentical and MUD (P = .56). Corresponding rates after RIC were 43% and 42% (P = .6). In this large multicenter case-matched retrospective analysis, despite the limitations of a registry-based study (ie, unavailability of key elements such as minimal residual disease testing), our analysis indicated that outcomes of patients with ALL undergoing HCT from a haploidentical donor were comparable with 8 of 8 MUD transplantations.

HSCT is curative in SCD. Patients with HLA-identical sibling donor have an excellent outcome ranging from 90%-100% overall and event-free survival. However, due to the lack of matched sibling donors this option is out of reach for 70% of patients with SCD. The pool of potential donors needs to be extended. Transplantations from HLA-matched unrelated donors were reported to be less successful with shorter event-free survival and higher incidences of complications including graft-vs-host disease, especially in patients with advanced stage SCD. Here we report transplantation outcomes for 25 children with SCD transplanted using HLA-matched grafts from related or unrelated donors. Overall survival was 100% with no severe (grade III-IV) graft-vs-host disease and a 12% rejection rate. Mixed donor chimerisms only occurred in transplantations from siblings, while transplantations from unrelated donors resulted in either complete donor chimerism or rejection. Despite the small patient number, overall and disease-free survival for unrelated donor transplantations is excellent in this cohort. The advanced disease state, higher alloreactive effect and stronger immunosuppression in unrelated donor transplantations raises patient risk, for which possible solutions could be found in optimization of transplant preparation, graft manipulation or haploidentical transplantation using T cell receptor ��/��-depleted grafts.

Outcome of 333 children with acute myeloid leukaemia relapsing after a first allogeneic haematopoietic stem cell transplantation was analyzed. Four-year probability of overall survival (4y-pOS) was 14%. 4y-pOS for 122 children receiving a second haematopoietic stem cell transplantation was 31% and 3% for those that did not (P=&nbsp

Introduction An HLA-matched unrelated donor (MUD) has been accepted as the next best option for patients who do not have a matched-related donor (MRD) available. However, identification of a MUD may be challenging due to donor availability for some populations. In addition, the MUD search and procurement of stem cell product usually takes much longer than that of a related donor, many patients may develop progressive disease or become medically unfit while waiting for a MUD transplant, which might have a negative impact on overall survival. Therefore, in this study we hypothesized that certain groups of patients may not benefit from performing a MUD search and sought to evaluate availability of a MUD donor, ability to proceed to transplant with a MUD, as well as transplant outcomes for all patients who had a MUD search started at our institution. Methods All consecutive patients with a diagnosis of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) who had a MUD search performed between 2013 and 2015 were included. All patients had high resolution HLA typing at HLA-A, -B, -C, -DRB1 and -DQB1 performed by DNA sequencing and had unrelated donor search by the NMDP. According to standard operating procedures, a MUD search was initiated when no MRD was available, or as soon as HLA typing was completed. If no 10/10 MUD was available, the choice between a 9/10 MUD, haploidentical or umbilical cord blood (UCB) was based on the treating physician's decision. Results The analysis included 242 patients with a median age of 58 years (range 9-80 years), 123 patients (51%) were male, 182 patients (75%) were Caucasian and 190 (79%) had common haplotypes. One hundred thirteen patients (47%), 35 (14%), 43 (18%) and 49 (20%) were in complete remission, primary induction failure (PIF), relapse/refractory and newly diagnosed, respectively. One hundred sixty (66%) patients had a 10/10 MUD identified. The majority of Caucasians (85%) had common haplotypes compared with only 58% of patients with other races (P Only 85 of 160 (53%) patients proceeded to MUD transplantation, while 66 (27%) patients received transplants from other donor types [9 (4%) 9/10 MUD, 20 (8%) haploidentical, 22 (9%) UCB and 15 (6%) MRD transplant], and 91 (38%) patients did not receive a transplant. The median time from MUD search to 10/10 MUD, MRD, haploidentical, 9/10 MUD and UCB transplant was 2.9, 2.3, 3.5, 4.6 3.2 months, respectively (P=0.002). Taken together, Caucasian race and having common haplotype were independently associated with 10/10 MUD identification with odds ratio (OR) of 6.8 (95%CI 3.1-14.9) and 39 (95%CI 13.9-110.4), respectively and with proceeding to MUD transplantation (OR 7.7, 95%CI 2.7-21.7 and OR 66, 95%CI 3.9->999), respectively. A multivariable analysis (MVA) for PFS of patients who received a transplant showed significant impact on transplant outcomes for disease status, cytogenetics and time from a MUD search to transplant, while donor type did not impact transplant PFS (Table 1). A second MVA for PFS was performed for all patients who had a MUD search. Patients who had intermediate/favorable cytogenetics, de novo AML, newly diagnosed/complete remission and received a transplant experienced significantly better PFS compared with their counterparts (Table 1, Figure 1). The highest percentages of 10/10 MUD identification, MUD transplant and PFS were observed for Caucasians who were newly diagnosed/complete remission with common haplotype (60% MUD identified, 69% MUD transplant, 3-year PFS rate of 46%), whereas the patient group with the lowest percentages was non-Caucasians with primary induction failure/relapsed/refractory and had uncommon haplotype (1% MUD identified, 0% MUD transplant, 3-year PFS rate of 0%). Conclusions Race, haplotype frequency and disease status at the time of MUD search influence probability to identify a MUD and receive a transplant. Patients with low likelihood to receive a MUD transplant may proceed to a haploidentical transplant as soon as indicated, as this approach does not appear to compromise transplant outcomes. Disclosures Konopleva: Stemline Therapeutics: Research Funding. Oran:AROG pharmaceuticals: Research Funding; Celgene: Consultancy, Research Funding; ASTEX: Research Funding. Champlin:Otsuka: Research Funding; Sanofi: Research Funding.

This article summarizes the recent development in the field of front-line unrelated donor transplantation for idiopathic aplastic anemia. The role of unrelated donor transplantation in the algorithm of pediatric aplastic anemia is reviewed and incorporates upfront unrelated donor transplantation. Newer strategies to delineate which children should receive immune suppression or transplantation are also discussed.

Introduction: Human leukocyte antigen (HLA)-matched unrelated donor (MUD) is the source of MUD transplantation (MUDT) for about 70% of patients who do not have matched related donor. To facilitate MUD search globally, there are 75 stem cell registries with more than 28 million donors registered (as of January 2017). Out of these donors, India has an insignificant representation of approximately 0.23 million. Further, Indians express high genetic variations, making it difficult to find MUD for an Indian patient. Aims and Objectives: The aim of this study is to analyze the MUD search for hematological disorder patients requiring transplant. An attempt was made to observe the MUD scenario for Indian patients requiring MUDT from accessible stem cell registries. Methods: A total of 558 patients approached Genebandhu registry and Chimera Transplant Research Foundation for MUD search over a period of 4 years requiring MUDT were included in this study. High resolution of HLA-A, -B, -C, -DRB1, and -DQB1 was used to perform MUD search through proprietary software called Prometheus and Bone Marrow Donors Worldwide (BMDW) search tool. Results: Out of 558 patients, MUD was located only for 135 (24.19%) patients. Out of these 135 patients, 91 (16.30%) patients found an MUD in global database and only 44 (7.88%) patients within India. Conclusion: This study demonstrates that building a large Indian database will not only help in increasing the chances of finding an MUD for maximum number of patients within India but also provide cost-effective treatment, in a society where cost is a vital factor.

Introduction: Data on the influence of different ATLG doses on immune reconstitution (IR) and GvHD in MUD allo-SCT is limited. In this study, we compared the impact of ATLG doses (30mg/kg vs 60 mg/kg) on IR and transplant outcomes. Methods: In this retrospective study we included 289 patients who received MUD allografts (HLA 10/10) between 2005-2019 in the University Cance Center University of Hamburg. All patients received PBSC-allo-SCT with MAC for various hematological malignancies. Seventy-three patients received 30mg/kg ATLG, and 216 patients received 60mg/kg (on days -3.-2 and -1) prior to allo-SCT. Periphereal blood samples were collected on days +30, +100 and +180 and analyzed by flow cytometry for following lymphocyte populations: T-cells (total and activated), T-helper cells (total, naïve and memory), cytotoxic T-cells (total, naïve and memory), B-Lymphocytes (total, naïve and memory), NK-cells, NKT-cells, γδT-cells and regulatory T-cells. Results: Neutrophil and platelet engraftments were significantly delayed after the 60mg/kg compared to 30mg/kg group with medians of 11 days (range, 8-23) vs 12 days (8-27) (p=0.009) for neutrophil and 14 days (range, 9-53) vs 16 days (range, 8-237) for platelets, respectively (p=0.002). We observed a higher incidence of EBV reactivation within the first 100 days in the 60mg/kg group (41% vs 21% in the 30mg/kg group, p=0.049). Higher cumulative incidence of Infections Day +100 was observed in the 60 mg/Kg group with an incidence of 75% vs that of 67% in the 30mg/Kg group respectively (p=0.002). At day +30 we observed a faster reconstitution of naïve-B cells (p The incidence of aGVHD grade II-IV was comparable between the groups: 63% and 59% in the 30mg/Kg and 60mg/Kg groups, respectively. We observed a higher incidence of grade IV aGvHD in the 30mg/kg group (8%) comparing with the rate of 0.5% in the 60mg/kg group (p=0.0002), this was confirmed in multivariate analysis: RR 0.65 (95%CI 0.005-0.363) p= 0.004. After a median follow up of 21 months (range, 1-161) there were no significant differences in OS, PFS, NRM, RI and cGVHD between the groups. Conclusion: The choice of ATLG dose has significant impact on IR after MUD-allo-SCT. Higher doses are associated with reduced severe aGVHD, however at the cost of delaying engraftment and increasing infections. Disclosures Ayuk: Celgene/BMS: Honoraria; Gilead: Honoraria; Janssen: Honoraria; Mallinckrodt/Therakos: Honoraria, Research Funding; Miltenyi Biomedicine: Honoraria; Novartis: Honoraria; Takeda: Honoraria.

Introduction Post-transplantation cyclophosphamide (PTCy) and calcineurin inhibitor (CNI) based GVHD prophylaxis has shown lower rates of acute and chronic GVHD when compared with the traditional prophylaxis of calcineurin inhibitor (CNI) and methotrexate (MTX) in matched donor (related and unrelated) allo-HCT. The combination of PTCy with sirolimus as a calcineurin inhibitor-free GVHD prophylaxis has shown promising results with cumulative rates of grade II-IV acute and chronic GVHD in the range of 15-27% and 20-27% respectively in patients undergoing matched and haploidentical allo-HCT. We report a single center, nonrandomized comparison of patients undergoing matched donor allo-HCT receiving PTCy in combination with sirolimus (PTCy/Siro) with those receiving the standard GVHD prophylaxis of tacrolimus and MTX (Tac/MTX). Methods One hundred and sixteen consecutive patients who had undergone a MRD or MUD allo-HCT between January 2018 to January 2021 and received either PTCy with sirolimus or tacrolimus with methotrexate as GVHD prophylaxis regimens were eligible for inclusion. The selection of PTCy with sirolimus or tacrolimus with methotrexate as GVHD prophylaxis regimen was based on physician choice. Primary endpoints were cumulative incidence of acute (grade II to IV) and chronic GVHD. Secondary endpoints were a) neutrophil and platelet engraftment; b) overall survival (OS); c) non-relapse mortality (NRM); d) relapse; e) clinical infections and f) time to immunosuppression (IS) withdrawal. Kaplan-Meier method was used to estimate 1-year and 2-year freedom from long term adverse events, including chronic GVHD, relapse, NRM and OS. All tests were two-sided with alpha level set at 0.05 for statistical significance. Results Out of a total of 116 patients undergoing MRD and MUD allo-HCT, 29 received PTCy/Siro and 87 Tac/MTX. Baseline characteristics were similar between the two arms except patients in PTCy/Siro were younger with median of 48 (range: 24-69) years vs. 61 (range: 20-73) years (p=0.004) in Tac/MTX. There was difference in primary indication for allo-HCT between the two arms with non-hodgkin lymphoma (NHL) being the most common in PTCy/Siro and acute myeloid leukemia (AML) in the Tac/MTX group. Patients receiving PTCy/Siro had a significantly higher median CD3 day 100 chimerism at 100 (90-100) vs. 90 (40-100) % ( Conclusion In this study, the combination of PTCy/Siro is associated with a significantly lower risk of chronic GVHD when compared against the traditional GVHD prophylaxis of CNI and methotrexate, despite significantly earlier IS withdrawal. Other long-term outcomes of interest remained comparable between the two arms. Chronic GVHD contributes to significant morbidity and mortality in patients undergoing allo-HCT. Newer strategies to limit the impact of chronic GVHD are needed. The results of our study warrant validation in a large, multicenter, randomized prospective trial. Figure 1 Figure 1. Disclosures Murthy: CRISPR Therapeutics: Research Funding. Foran: gamida: Honoraria; takeda: Research Funding; novartis: Honoraria; trillium: Research Funding; boehringer ingelheim: Research Funding; OncLive: Honoraria; abbvie: Research Funding; certara: Honoraria; sanofi aventis: Honoraria; syros: Honoraria; taiho: Honoraria; revolution medicine: Honoraria; bms: Honoraria; servier: Honoraria; pfizer: Honoraria; actinium: Research Funding; aptose: Research Funding; kura: Research Funding; h3bioscience: Research Funding; aprea: Research Funding; sellas: Research Funding; stemline: Research Funding.

Introduction: Post-transplant cyclophosphamide (PTCy) is a standard GVHD prophylactic approach for haploidentical hematopoietic cell transplantation (haploHCT). Retrospective studies in patients with lymphoma showed lower chronic GVHD in haploHCT with PTCy-based GVHD prophylaxis compared to matched unrelated donor (MUD) HCT with calcineurin-based GVHD prophylaxis (+/- ATG). Recent retrospective studies showed that using MUD donors was better than haplo donors when PTCy and reduced-intensity conditioning are used for ALL, AML or MDS. However, no studies to date have compared haploHCT and MUD HCT when PTCy is used in the setting of lymphomas. Methods: 2155 adults (730 CIBMTR, 1425 EBMT) aged =/>18 years who received their first haploHCT or MUD HCT (8/8 match at HLA-loci A, B, C and DRB1) using PTCy from 2010-2019 for lymphoma were included. The majority of both MUD (n=312; 14%) and haplo (n=1843; 86%) HCTs received reduced intensity/non-myeloablative conditioning (n=1655; 77%) using a peripheral blood stem cell graft (n=1379; 64%) and a three-drug GVHD prophylaxis (PTCy + calcineurin inhibitor + MMF, n=1805; 84%). Hodgkin's lymphoma was the most common indication (n=899; 42%) followed by diffuse large B-cell lymphoma (n=525; 24%), T-cell lymphomas (n=328; 15%), mantle cell lymphoma (n=234; 11%) and follicular lymphoma (n=169; 8%). Most had chemosensitive disease at transplant (n=1781; 83%). Some main characteristics of the two cohorts are shown in Figure 1. Median follow-up among survivors was longer for haplo-HCT (36 and 31 months for the CIBMTR and EBMT cohort, respectively) than MUD-HCT (24 and 17 months, respectively). Cox proportional hazards models were built using stepwise forward and backward selection with a selection/retention threshold of 0.05. Any clinical variables that did not meet the proportional hazard assumption were adjusted for by stratification, and regression models were built to compare outcomes between donor types. Center effect was adjusted in all the models. Results: Figures 2 and 3 show the multivariate analysis results. Overall survival was 73% (71-75%) at 1 year and 65% (63-67%) at 2 years. Relapse was 21% (20-23%) at 1 year and 26% (24-28%) at 2 years. All outcomes favored MUD over haplo donors with the use of PTCy-based GVHD prophylaxis for both. Conclusions: Patients with lymphoma receiving PTCy HCT from MUDs demonstrated better outcomes than those with haplo donors in this retrospective study of CIBMTR and EBMT data Future prospective studies are needed to confirm and clarify the reasons for these differences. Figure 1 Figure 1. Disclosures Mussetti: GILEAD: Other: Clinical trials participation, Research Funding; TAKEDA: Honoraria; NOVARTIS: Honoraria, Other: Clinical trials participation. Hamadani: Janssen, Incyte, ADC Therapeutics, Omeros, Morphosys, Kite: Consultancy; Sanofi, Genzyme, AstraZeneca, BeiGene: Speakers Bureau; Takeda, Spectrum Pharmaceuticals and Astellas Pharma: Research Funding. Glass: Novartis: Consultancy; Riemser: Research Funding; Helios Klinik Berlin-Buch: Current Employment; Kite: Consultancy; Roche: Consultancy, Research Funding, Speakers Bureau; BMS: Consultancy. Blaise: Jazz Pharmaceuticals: Honoraria. Paczesny: Medical University of South Carolina: Patents & Royalties: inventor on the ST2 bispecific antibody patent application. Dreger: Novartis: Consultancy, Speakers Bureau; Riemser: Consultancy, Research Funding, Speakers Bureau; BMS: Consultancy; Bluebird Bio: Consultancy; AstraZeneca: Consultancy, Speakers Bureau; Gilead Sciences: Consultancy, Speakers Bureau; Janssen: Consultancy; AbbVie: Consultancy, Speakers Bureau; Roche: Consultancy, Speakers Bureau. Lee: AstraZeneca: Research Funding; Incyte: Research Funding; Janssen: Other; Kadmon: Research Funding; National Marrow Donor Program: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Syndax: Research Funding; Pfizer: Research Funding; Takeda: Research Funding; Amgen: Research Funding. Sureda: BMS/Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings and/or travel, Speakers Bureau; Bluebird: Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings and/or travel, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kite, a Gilead Company: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Consultancy, Honoraria, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Mundipharma: Consultancy; Roche: Other: Support for attending meetings and/or travel; GSK: Consultancy, Honoraria, Speakers Bureau.