Abstract Autologous stem cell transplantation (auto‐SCT) is an established treatment for peripheral T‐cell lymphoma (PTCL) to consolidate first remission and for patients with relapsed/refractory (r/r) disease. We aimed to examine the outcomes of patients with PTCL NOS, AITL, and ALK‐negative ALCL undergoing auto‐SCT between 2010 and 2022 and reported to EBMT. Adult patients with major T‐cell entities who had received auto‐SCT either up‐front or for r/r disease were included. 2082 patients underwent up‐front and 1249 salvage auto‐SCT. Three‐year progression‐free (PFS) and overall survival (OS) after up‐front auto‐SCT were 55.2% and 73.1%. For r/r patients, 3‐year PFS and OS were 42.6% and 59.5%. In multivariate analysis, male patients, histology other than ALK‐negative ALCL, non‐CR, and higher age at auto‐SCT showed significantly lower PFS and OS after both, up‐front and salvage auto‐SCT, mostly reflecting the higher relapse incidence for these patients. Major outcomes did not significantly change when the analyses were restricted to the patients with PET‐based response at auto‐SCT (n = 2062). Auto‐SCT demonstrated excellent outcomes when used up‐front and surprisingly good results in salvage settings. Patients with ALK‐negative ALCL survived significantly better than patients with PTCL NOS or AITL. Male gender, higher age, and non‐CR at auto‐SCT were associated with poor outcomes. Overall, auto‐SCT is a valid treatment option in T‐cell lymphoma where targeted therapies still play a limited role.
BACKGROUND:Graft rejection (GR) is common complication after haploidentical hematopoietic cell transplantation (haplo-HCT). There are only a few studies describing the clinical presentation and potential risk factors of GR, and the optimal rescue strategy is not established. OBJECTIVES:To evaluate the cumulative incidence and potential risk factors for GR following haplo-HCT, and to compare survival, clinical symptoms, selected inflammatory parameters, and lactate dehydrogenase levels in patients with and without GR. METHODS:A retrospective single-center study including 79 patients (59 children and 20 adults) who underwent ex vivo T-cell-depleted haplo-HCT at Skåne University Hospital from 2001 to 2020. RESULTS:The cumulative incidence of GR was 14.8% (95% CI: 7.1-22.6). The median time to GR was 21 days (13-31). Five-year overall survival for patients without GR was 45.3% (95% CI: 32.8-57.7), and 41.7% (95% CI: 13.8-69.9) for those with GR (P = n.s.). None of the analyzed patient- and transplant-related factors were significantly associated with GR. Macular rash was the only GR-associated symptom. Patients with GR had higher median ferritin (18,096 µg/L; 1412-95,980) and lactate dehydrogenase (10.5 µkat/L, 0.7-35.0), and lower fibrinogen (2.65 g/L; 0.9-3.9) levels then patients who engrafted. CONCLUSIONS:In our cohort, GR was not associated with inferior survival and prompt retransplantation seems to be an effective rescue strategy. GR is characterized by increased levels of inflammation markers, while clinical symptoms are nonspecific. Further analysis in a larger cohort is necessary to assess whether regular monitoring of inflammatory parameters could guide preemptive treatment strategies for GR.
The aim was to describe hematopoietic stem cell (HSC) donors' experiences focusing on information and side effects during the first year after donation. Our prospective Swedish cohort study with adult HSC donors was performed from 2019 to 2022, with questionnaires at four time points from before until 12 months after donation. 173 unrelated and 68 related donors participated, and the majority donated peripheral blood stem cells. All but one rated their donation experience as good or very good. At least one side effect was reported by 83% of participants. Six donors (2.5%) experienced either numerous side effects, at least one severe side effect, or prolonged side effects. Satisfaction with information was lower among donors having severe side effects and bone marrow donors. Overall satisfaction with the donation was lower among donors having severe side effects and unrelated donors. Donors were generally satisfied with the pre-donation information. Most experienced side effects that resolved within 2 weeks, which strengthens the case for unchanged donor follow-up 1 month after donation, with individualized follow-up for donors with persistent symptoms. Enhanced information regarding the risk of more severe or prolonged side effects appears warranted, and its effect on donor satisfaction should be evaluated.
Autologous hematopoietic cell transplants (auto-HCTs) remain the standard of care for transplant-eligible MM patients. The general practice has been to undergo upfront apheresis following induction to collect sufficient number of CD34+ cells to facilitate two auto-HCTs. However, 5-30% of MM patients do not initially mobilise a sufficient number of hematopoietic stem cells and are classified as poor mobilizers (PM). We compared the baseline characteristics and outcomes of 61 PMs and 816 non-PM patients who underwent a second auto-HCT and who were enrolled in the non-interventional CALM study (NCT01362972). Only patients who collected CD34+ prior to auto-HCT1 were included. Auto-HCT2 comprised both tandem and salvage transplants. PMs were re-mobilized with plerixafor (n = 24, 39.3%) or non-plerixafor-based regimens (n = 37, 60.7%). There were no significant differences in engraftment, progression-free survival (PFS) or overall survival (OS) after the second auto-HCT between PM and non-PM patients. There was a trend to shorter PFS in PM patients undergoing salvage auto-HCT (median 9.6 vs. 12.9 months; p = 0.08) but no significant difference in OS. The median OS was 41.1 months for PM and 41.2 months for non-PM patients (p = 0.86). These data suggest that salvage mobilization is effective and does not affect overall outcomes after a second auto-HCT.
IntroductionHLA compatibility is a mainstay in allogeneic HCT, resulting in a preference for well-matched unrelated donors (UD). Recent interest in improving accessibility for patients lacking a fully matched donor and the introduction of post-transplant cyclophosphamide (PTCy) for GvHD prophylaxis are increasing the use of mismatched (i.e. <10/10) UD. However, the role of HLA mismatching in current HCT practice, including PTCy, remains unclear.MethodsWe studied outcomes in 17,276 adult patients reported to the EBMT Registry who underwent UD-HCT between 2005-2020. Most patients were treated for AML, ALL, MDS, or MPN (67.5%) using reduced-intensity conditioning (56%) and in vivo T-cell depletion (76%). 23.5% of the transplants had one (9/10; n=3,561) or two (8/10; n=499) high-resolution HLA mismatches (mM). GvHD prophylaxis with calcineurin inhibitors was used in all patients. PTCy was used in 7% (n=924) of the 10/10 and 15% (n=599) of the <10/10 transplants. Multivariable models were constructed to analyze the effect of the number, class, locus, and nature (i.e. high vs low-resolution) of mM in the presence or absence of PTCy.ResultsOS was significantly lower in transplants across HLA mM (45% [95% CI 40-50%] in 8/10 and 47% [45-49%] in 9/10 vs 52% [51-53%] in 10/10 at 60 months; p<0.001; Figure 1a). In multivariable analysis, the presence of one (HR 1.24 [99% CI 1.15-1.34]; p<0.001) or two (HR 1.29 [1.09-1.54]; p<0.001) mM associated with higher risks of mortality compared to 10/10 transplants. HLA class I (HR 1.31 [1.20-1.42]; p<0.001) but not HLA class II mM (HR 1.07 [0.93-1.22]; p=0.23) were associated with significantly worse OS, even when excluding antigen recognition domain-matched pairs. For class I, HLA-A (HR 1.37 [1.21-1.54]; p<0.001) and HLA-B (HR 1.44 [1.23-1.69]; p<0.001) mM conferred higher risks than HLA-C mM (HR 1.16 [1.01-1.33]; p=0.005), and antigen-level mM associated with worse OS than allelic mM (HR 1.22 [1.01-1.46]; p=0.006). Similar associations were observed for GRFS, RFS, NRM, and aGVHD, but no significant differences were observed for relapse or chronic GvHD. Non-permissive HLA-DPB1 mM increased aGvHD risks in both 9/10 and 10/10 pairs, but NRM only in the latter. The use of PTCy significantly reduced the risks of GvHD and mortality compared to standard prophylaxis. However, the effects of HLA mM were similar regardless of PTCy use (non-significant interaction; p=0.22), with a single mM conferring significantly increased risks of mortality both in the presence (HR 1.38 [1.14-1.68]; p<0.001) and absence (HR 1.23 [1.13-1.33]; p<0.001) of PTCy (Figure 1b).ConclusionIn contemporary HCT, HLA disparity is associated with increased risks of mortality, mainly driven by HLA class I. These associations are present even under GvHD prophylaxis with PTCy, highlighting the need to continue defining better tolerated mM to provide the best possible outcome for all patients.
BACKGROUND:A growing evidence base supports the use of autologous haematopoietic stem cell transplantation (aHSCT) for treatment of relapsing-remitting multiple sclerosis (RRMS), but it has not yet been integrated into most national clinical guidelines. The objective of this study was to assess efficacy and safety when aHSCT is implemented in routine healthcare. METHODS:We assessed 231 patients and the final analysis included 174 RRMS patients who were treated with aHSCT in Sweden before 1 January 2020. Efficacy was evaluated by performing a retrospective analysis of prospectively collected data from the Swedish MS registry. Procedure-related safety was assessed by analysing data from electronic patient records covering a period of 100 days following aHSCT. RESULTS:With a median follow-up time of 5.5 (IQR: 3.4-7.5) years, the Kaplan-Meier estimate for no evidence of disease activity was 73% (95% CI 66% to 81%) at 5 years and 65% (95% CI 57% to 75%) at 10 years. Out of the 149 patients with baseline disability, 80 (54%) improved, 55 (37%) were stable and 14 (9%) deteriorated. The mean number of adverse events per patient was 1.7 (±SD: 1.5) for grade 3 events and 0.06 (±SD: 0.3) for grade 4 events. Febrile neutropenia was the most common adverse event, affecting 68% of patients. There was no treatment-related mortality. CONCLUSIONS:Treatment with aHSCT for RRMS is associated with freedom from disease activity in a majority of patients, with acceptable adverse events. This procedure should be considered a standard of care for patients with highly active RRMS.
SummaryAllogeneic haematopoietic cell transplantation (allo‐HCT) remains an option for tyrosine kinase inhibitor‐resistant chronic myeloid leukaemia (CML) in first chronic phase (CP1) and high‐risk patients with advanced disease phases. In this European Society for Blood and Marrow Transplantation (EBMT) registry‐based study of 1686 CML patients undergoing first allo‐HCT between 2012 and 2019, outcomes were evaluated according to donor type, particularly focusing on mismatched related donors (MMRDs). Median age at allo‐HCT was 46 years (IQR 36–55). Disease status was CP1 in 43%, second CP (CP2) or later in 27%, accelerated phase in 12% and blast crisis in 18%. Donor type was matched related (MRD) in 39.2%, MMRD in 8.1%, matched unrelated (MUD) in 40.2%, and mismatched unrelated (MMUD) in 12.6%. In 4 years, overall survival (OS) for MRD, MMRD, MUD and MMUD was 61%, 56%, 63% and 59% (p = 0.21); relapse‐free survival (RFS) was 48%, 42%, 52% and 46% (p = 0.03); cumulative incidence of relapse (CIR) was 33%, 37%, 27% and 30% (p = 0.07); non‐relapse mortality (NRM) was 19%, 21%, 21% and 24% (p = 0.21); and graft‐versus‐host disease (GvHD)‐free/relapse‐free survival (GRFS) was 16%, 18%, 22% and 15% (p = 0.05) respectively. On multivariate analysis, MMRD use associated with longer engraftment times and higher risk of graft failure compared to MRD or MUD. There was no statistical evidence that MMRD use associated with different OS, RFS and incidence of GvHD compared to other donor types.
PURPOSEHuman leukocyte antigen (HLA) mismatching can reduce survival of patients with blood cancer after hematopoietic cell transplantation (HCT). How recent advances in HCT practice, in particular graft-versus-host disease (GVHD) prophylaxis by post-transplantation cyclophosphamide (PTCy), influence HLA risk associations is unknown.PATIENTS AND METHODSThe study included 17,292 unrelated HCTs with 6-locus high-resolution HLA typing, performed mainly for acute leukemia or related myeloid neoplasms between 2016 and 2020, including 1,523 transplants with PTCy. HLA risk associations were evaluated by multivariable Cox regression models, with overall survival (OS) as primary end point.RESULTSOS was lower in HLA mismatched compared with fully matched transplants (hazard ratio [HR], 1.23 [99% CI, 1.14 to 1.33]; P < .001). This was driven by class I HLA-A, HLA-B, HLA-C (HR, 1.29 [99% CI, 1.19 to 1.41]; P < .001) but not class II HLA-DRB1 and HLA-DQB1 (HR, 1.07 [99% CI, 0.93 to 1.23]; P = .19). Class I antigen-level mismatches were associated with worse OS than allele-level mismatches (HR, 1.36 [99% CI, 1.24 to 1.49]; P < .001), as were class I graft-versus-host peptide-binding motif (PBM) mismatches compared with matches (HR, 1.42 [99% CI, 1.28 to 1.59]; P < .001). The use of PTCy improved GVHD, relapse-free survival compared with conventional prophylaxis in HLA-matched transplants (HR, 0.77 [0.66 to 0.9]; P < .001). HLA mismatching increased mortality in PTCy transplants (HR, 1.32 [1.04 to 1.68]; P = .003) similarly as in non-PTCy transplants (interaction P = .43).CONCLUSIONClass I but not class II HLA mismatches, especially at the antigen and PBM level, are associated with inferior survival in contemporary unrelated HCT. These effects are not significantly different between non-PTCy compared with PTCy transplants. Optimized HLA matching should still be considered in modern HCT.
Background: Ide-cel and cilta-cel received regulatory approval for the treatment of patients with relapsed or refractory multiple myeloma (MM) after ≥4 prior lines of therapy, and almost all eligible patients in the US and Europe have previously received at least one autologous hematopoietic cell transplant (autoHCT). Even for those who received upfront autoHCT, salvage transplant (either second autoHCT or allogeneic HCT) for patients with relapsed MM was shown to be effective and feasible. Therefore, comparing CAR-T cell therapy with salvage transplant could facilitate future selection of patients with relapsed MM, as eligibility for transplant (especially allogeneic HCT) differs significantly from that of CAR-T. Methods: We leveraged a large European dataset to identify relapsed MM patients who received either salvage autoHCT, allogeneic HCT, or CAR-T cell therapy. To minimize selection bias, we only included patients who received salvage treatment from 2018 onwards and who had documented time of relapse. Furthermore, to control for differences in patient characteristics, we applied propensity score (PS) matching for the comparison: CAR-T versus auto HCT and versus allogeneic HCT. We performed individual matching with the “nearest neighbour” method, using a caliper=0.2. The model for PS estimation included patient sex, MM classification at diagnosis, previous transplant history (single or tandem auto), interval between upfront transplant and relapse and between relapse and CAR-T/salvage transplant, age, performance status and disease status at CAR-T/salvage transplant. Endpoints of matched groups were compared by Log-Rank test or Gray test stratified on the pair. Primary endpoint was progression-free survival (PFS) at 1 year with 95% confidence interval (CI). Secondary endpoints constituted non-relapse mortality, incidence of relapse, and overall survival (OS). Results: We included 4292 patients, of whom 3858 received salvage autoHCT, 371 allogeneic HCT, and 63 CAR-T cell therapy (60% ide-cel, 33% cilta-cel, 7% other investigational). Median age at time of salvage treatment was 62 years for autoHCT, 54 years for allogeneic HCT, and 61 years for CAR-T cell therapy (P<0.001). More than 60% of patients were male in all groups, and IgG subtype of MM was present in 52% of autoHCT, 48% of allogeneic HCT, and 44% of CAR-T cell therapy. More patients receiving CAR-T cell therapy had a Karnofsky performance status <80% (41%) versus 32% of autoHCT and 29% of allogeneic HCT. In terms of response, complete response to treatment was observed in 40% for autoHCT, 63% for allogeneic HCT, and 44% for CAR-T cell therapy. Partial remission or very good partial remission was achieved 11%, 9%, and 35%, respectively (P<0.001). Median follow-up was 16.7 months for the entire cohort. The PS method could successfully match almost all patients for the comparison of CAR-T cell therapy versus salvage autoHCT (59 patient, respectively). The 1-year PFS for CAR-T cell therapy versus autoHCT was 68% (95% CI, 56-80%) versus 44% (95% CI, 28-59%; P=0.048; Figure 1). The 1-year non-relapse mortality was 9% (95% CI, 2-17%) versus 0% (P=0.31). Cumulative incidence of relapse at 1 year was 23% versus 57% (P=0.028), and 1-year overall survival was 81% versus 68% (P=0.059). The PS method matched 33 patients for the comparison of CAR-T cell therapy versus salvage allogeneic HCT. The 1-year PFS was 72% (95% CI, 56-88%) versus 39% (95% CI, 18-60%; P=0.346). Non-relapse mortality at 1-year was 13% (95% CI, 1-25%) versus 23% (95% CI, 7-43%; P=0.257). The 1-year cumulative incidence of relapse was 15% versus 36% (P=0.763), and the 1-year overall survival was 84% (95% CI, 71-97%) versus 60% (95% CI, 39-81%; P=0.083). Conclusion: This multicenter retrospective study compared CAR-T cell therapy with salvage transplantation strategies for relapsed MM. CAR- T cell therapy appeared to improve outcomes, especially in comparison with salvage autoHCT. The higher absolute rates of non-relapse mortality observed with CAR-T cell therapy may not counterbalance overall beneficial results, and rather highlights the need for careful selection of patients. Longer follow-up will be needed for definitive results.
Introduction COVID-19 has been associated with high morbidity and mortality in allogeneic hematopoietic stem cell transplant (allo-HCT) recipients. Methods This study reports on 986 patients reported to the EBMT registry during the first 29 months of the pandemic. Results The median age was 50.3 years (min – max; 1.0 – 80.7). The median time from most recent HCT to diagnosis of COVID-19 was 20 months (min – max; 0.0 – 383.9). The median time was 19.3 (0.0 - 287.6) months during 2020, 21.2 (0.1 - 324.5) months during 2021, and 19.7 (0.1 – 383.9) months during 2022 (p = NS). 145/986 (14.7%) patients died; 124 (12.6%) due to COVID-19 and 21 of other causes. Only 2/204 (1%) fully vaccinated patients died from COVID-19. There was a successive improvement in overall survival over time. In multivariate analysis, increasing age (p<.0001), worse performance status (p<.0001), contracting COVID-19 within the first 30 days (p<.0001) or 30 – 100 days after HCT (p=.003), ongoing immunosuppression (p=.004), pre-existing lung disease (p=.003), and recipient CMV seropositivity (p=.004) had negative impact on overall survival while patients contracting COVID-19 in 2020 (p<.0001) or 2021 (p=.027) had worse overall survival than patients with COVID-19 diagnosed in 2022. Discussion Although the outcome of COVID-19 has improved, patients having risk factors were still at risk for severe COVID-19 including death.
Integrating biological HLA-DPB1 mismatch models to predict survival after unrelated hematopoietic cell transplantation Relapse and graft-versus-host disease (GvHD) are the main impediments to the clinical success of allogeneic hematopoietic cell transplantation (HCT) in curing malignant blood disorders.Alloreactive donor T cells are important mediators of both relapse control by graft-versus-leukemia (GvL) effects, and of GvHD. 1 In unrelated donor (UD)-HCT, frequent human leukocyte antigen (HLA)-DPB1 disparity is the target of T-cell alloreactivity, contributing to both leukemia control and GvHD. 2 We have previously shown that two biological models of HLA-DPB1 mismatching, namely permissiveness according to T-cell epitope (TCE) groups and genetically determined high-expression levels, are individually associated with the risks of non-relapse mortality and GvHD/relapse, respectively. 3,4This led us to hypothesize that combined TCE-permissive and high-expression (TPHE) HLA-DPB1 mismatches might synergize for best outcomes.We tested this novel hypothesis in over 6,000 HCT from 8/8 HLA-matched UD reported to the European Group for Blood and Marrow Transplantation (EBMT), to demonstrate that HLA-DPB1 non-TPHE mismatches were associated with worse relapse-free survival and overall survival than TPHE mismatches, present in 21.7% of single HLA-DPB1 disparate pairs.Our work provides a synthesis of previous algorithms, mechanistically based on HLA-DPB1 immunopeptidome divergence 5 and expression by residual leukemia cells, 6,7 respectively, into a new and integrative model for intelligent mismatching in UD-HCT, to improve survival for future patients.Alloreactive donor T cells recognizing patient-specific genetic polymorphisms, including mismatched HLA allotypes, play a major role in both beneficial GvL and severe GvHD after UD-HCT.One of the best examples of these two contrasting aspects of T-cell alloreactivity is donorrecipient HLA-DPB1 disparity, present in over 80% of transplants from UD. 3 HLA-DPB1 disparity has been extensively explored for biological models apt to tease out clinically permissive mismatch combinations. 2These include sharing of alloreactive TCE groups between mismatched HLA-DPB1 alleles (TCE-permissiveness), mainly associated with non-relapse mortality, 3,8 and high or low expression levels determined by a specific single nucleotide polymorphism in the HLA-DPB1 3' untranslated region (expression-permissiveness), mainly associated with acute GvHD. 4,9Numerous studies have since investigated the clinical role of these two models in different national
Introduction: Graft-versus-host disease (GvHD) is a multi-systemic disorder affecting patients who undergo allogenic hematopoietic stem cell transplantation (allo-HSCT) and is associated with considerable morbidity and mortality both in its acute (a) and chronic (c) forms, particularly in patients with steroid-refractory (SR)-GvHD (Flinn AM and Gennery AR. Fac Rev 2023).Given the lack of real-life data on GvHD, this study was conducted using a large European database with the objective to provide evidence on the epidemiology and treatment patterns in patients with aGvHD, cGvHD, and SR-GvHD. Methods: This retrospective, observational cohort study was conducted between July 1, 2014 and December 31, 2020 in allo-HSCT patients registered to the European Society for Blood and Marrow Transplantation (EBMT) database. Male or female patients aged ≥12 years at index (≥18 years for SR-GvHD and ruxolitinib [RUX] cohorts) who had received ≥1 allo-HSCT during this study period (January 1, 2017 to July 1, 2019 for SR-GvHD and RUX cohorts) were included in the study population. The EBMT cohort included all allo-HSCT patients, irrespective of GvHD development post-transplant (Tx). The primary objective was to assess the cumulative incidence of aGvHD and cGvHD in patients from the EBMT cohort who met the inclusion criteria. Overall survival of patients up to 60 months was also assessed in the EBMT cohort. The SR-GvHD cohort comprised a sub-selection of GvHD patients (from selected EBMT centers) who were diagnosed with SR-aGvHD, SR-cGvHD, or both, some receiving RUX as treatment; from the SR-GvHD cohort, a sub-selection of patients who had been treated with RUX for aGvHD and/or cGvHD, irrespective of treatment line, were included in the RUX cohort. Results:In the EBMT database, 60,140 patients had received an allo-HSCT. Most patients (94.5%) underwent 1 allo-HSCT, the remaining had >1 procedure. The EBMT cohort included a higher proportion of male patients between 50 and 69 years (Table 1). The main indication for allo-HSCT was acute leukemia. At the time of Tx, most patients were in their early disease stage and had unrelated donors(Table 1). The cumulative incidence of aGvHD was 27.9% and 27.6%, 4 months after first and second Tx, respectively. The cumulative incidence of cGvHD was 37.4% and 29.7%, 60 months after first and second Tx, respectively. aGvHD was of grade 2-4 in 27.1% of patients, and the most affected organ was skin (33.6%, grade 2-4: 19.5%) followed by liver (4.0%, grade 2-4: 2.3%) and gut (4.6%, grade 2-4: 2.8%); however, organ involvement was not collected in many patients. The cGvHD was limited (13.6%), extensive (14.7%) or of unknown grade (3.1%). Graft failure occurred in 5.9% of patients. The overall survival of EBMT cohort patients at 60 months was 53.1% with a median follow-up time of 32.9 months. The most frequent cause of death was relapse/progression (30.6%) followed by infection (27.1%) and GvHD (19.1%). The EBMT registry contains more SR-GvHD patients but only for subset of 292 SR-GvHD patients, additional information was obtained, of which 37 (34.6%) patients were treated with RUX and 70 (65.4%) with other second-line (2L) treatment for SR-aGvHD. For SR-cGvHD, 59 (31.9%) received RUX and 126 (68.1%) other 2L treatment. Baseline characteristics were comparable between SR-GvHD and the EBMT cohort (Table 1). Within SR-GvHD treatment groups, overall, the baseline characteristics were comparable across RUX and other 2L, and consistent with the EBMT and SR-GvHD cohorts. Compared with other 2L treatment, a slightly higher proportion of RUX-treated patients were females in SR-aGvHD cohort and males in SR-cGvHD cohort. While the most common first-line treatment for aGvHD in both RUX and the other group was methylprednisolone, for SR-cGvHD, it was prednisone+cyclosporine in RUX and prednisone in the other group. Conclusion:This large retrospective real-world evidence study from the EBMT reports on patients with GvHD after allo-HSCT. The cumulative incidence of aGvHD at 4 months post-Tx and cGvHD at 60 months was similar after the first or the second Tx. Though this study provides valuable insights on the epidemiology and treatment patterns of SR-GvHD patients, interpretation of these data is limited due to the small sample size of RUX and other treatment groups compared with the EBMT cohort.