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Background: The optimal choice for graft‐versus‐host disease (GVHD) prophylaxis in haploidentical stem cell transplantation (haplo‐SCT) remains debatable. Posttransplant cyclophosphamide (PTCy) and anti‐thymocyte globulin (ATG) are two common strategies, but little is known about their combination. Methods: Using the European Society for Blood and Marrow Transplantation (EBMT) registry, the authors identified 3649 adult patients with acute myeloid leukemia (AML) who underwent haplo‐SCT in complete remission between 2007 and 2021 at 260 EBMT‐participating centers who received either PTCy (n = 2999), ATG (n = 358), or combination prophylaxis (n = 292). Cord blood transplants, combined bone marrow and peripheral grafts, and transplants with ex vivo graft manipulation were excluded. Median follow‐up was 31.8 months. Results: On multivariate analysis, adjusting for patient age and performance status, disease status at transplant, cytogenetic risk, conditioning intensity, stem cell source, female‐to‐male graft, and donor and patient CMV status, we present the following. Compared to PTCy, ATG had a higher risk of nonrelapse mortality (hazard ratio [HR], 1.6; p =.003), worse leukemia‐free survival (HR, 1.4; p =.002), overall survival (HR, 1.49; p =.0009), and GVHD‐free and relapse‐free survival (HR, 1.29; p =.012). The combination of PTCy and ATG, however, led to significantly reduced rates of grade 2–4 (HR, 0.51; p =.0003) and grade 3–4 (HR, 0.5; p =.018) acute GVHD and did not affect any transplant outcomes compared to PTCy without ATG. Conclusion: The authors conclude that ATG alone is a less effective prophylaxis strategy compared to PTCy, however, the combination of PTCy and ATG is superior to either monotherapy. They propose that this combination could be considered a potential new standard of care for GVHD prophylaxis in haplo‐SCT for AML. This study analyzed 3649 adult acute myeloid leukemia (AML) patients undergoing haploidentical stem cell transplantation (haplo‐SCT) with either posttransplant cyclophosphamide (PTCy), anti‐thymocyte globulin (ATG), or their combination, and showed that ATG alone had worse outcomes compared to PTCy, but combining PTCy and ATG significantly reduced acute graft‐vs‐host disease (GVHD) rates without affecting transplant outcomes. This suggests the PTCy and ATG combination could be a superior GVHD prophylaxis strategy in haplo‐SCT for AML. [ABSTRACT FROM AUTHOR]

Introduction: For the majority of patients with acute myeloid leukemia (AML) an allogeneic stem cell transplant (SCT) in first complete remission (CR) is preferred. However, whether the number of courses required to achieve CR has a prognostic impact is unclear. It is unknown which factors remain important in patients requiring more than one course of induction to attain remission. Methods: This Acute Leukaemia Working Party study from the European Society for Blood and Marrow Transplantation identified adults who received an allograft in first CR from either a fully matched sibling or 10/10 or 9/10 human leucocyte antigen (HLA)‐matched unrelated donor (HLA‐A, HLA‐B, HLA‐C, HLA‐DR, or HLA‐DQ). Univariate and multivariate analyses were undertaken to identify the prognostic impact of one or two courses of induction to attain CR. Results: A total of 4995 patients were included with 3839 (77%) patients attaining a CR following one course of induction chemotherapy (IND1), and 1116 patients requiring two courses (IND2) to attain CR. IND2 as compared to IND1 was a poor prognostic factor in a univariate analysis and remained so in a multivariate Cox model, resulting in an increased hazard ratio of relapse (1.38; 95% confidence interval [CI], 1.16–1.64; p =.0003) and of death (1.27; 95% CI, 1.09–1.47; p =.002). Adverse prognostic factors in a multivariate analysis of the outcomes of patients requiring IND2 included age, FLT3‐ITD, adverse cytogenetics, and performance status. Pretransplant measurable residual disease retained a prognostic impact regardless of IND1 or IND2. Conclusion: Initial response to chemotherapy as determined by number of courses to attain CR, retained prognostic relevance even following SCT in CR. Patients requiring two courses of induction to attain complete remission (CR) have a higher incidence of relapse and inferior survival as compared to those who require one course. Pretransplant measurable residual disease remains important in predicting outcomes following an allogeneic stem cell transplant in those requiring two courses of induction to achieve CR. [ABSTRACT FROM AUTHOR]

Autologous(auto-) and allogeneic(allo-) hematopoietic stem cell transplantation (HSCT) are key treatments for relapsed/refractory diffuse large B-cell lymphoma (DLBCL), although their roles are challenged by CAR-T-cells and other immunotherapies. We examined the transplantation trends and outcomes for DLBCL patients undergoing auto-/allo-HSCT between 1990 and 2021 reported to EBMT. Over this period, 41,148 patients underwent auto-HSCT, peaking at 1911 cases in 2016, while allo-HSCT saw a maximum of 294 cases in 2018. The recent decline in transplants corresponds to increased CAR-T treatments (1117 cases in 2021). Median age for auto-HSCT rose from 42 (1990–1994) to 58 years (2015–2021), with peripheral blood becoming the primary stem cell source post-1994. Allo-HSCT median age increased from 36 (1990–1994) to 54 (2015–2021) years, with mobilized blood as the primary source post-1998 and reduced intensity conditioning post-2000. Unrelated and mismatched allo-HSCT accounted for 50% and 19% of allo-HSCT in 2015–2021. Three-year overall survival (OS) after auto-HSCT improved from 56% (1990–1994) to 70% (2015–2021), p < 0.001, with a decrease in relapse incidence (RI) from 49% to 38%, while non-relapse mortality (NRM) remained unchanged (4%). After allo-HSCT, 3-year-OS increased from 33% (1990–1999) to 46% (2015–2021) (p < 0.001); 3-year RI remained at 39% and 1-year-NRM decreased to 19% (p < 0.001). Our data reflect advancements over 32 years and >40,000 transplants, providing insights for evaluating emerging DLBCL therapies. [ABSTRACT FROM AUTHOR]

A study published in the Blood Cancer Journal examined the outcomes of allogeneic hematopoietic stem cell transplantation (HCT) in adult patients with adverse-risk acute myeloid leukemia (AML) and KMT2A rearrangement. The study found that haploidentical donor HCT (Haplo-HCT) had a lower relapse incidence compared to matched sibling donor (MSD) or matched unrelated donor (MUD) transplants. The study also investigated the prognostic value of different KMT2A fusion partners. The findings suggest that Haplo-HCT may be beneficial for AML patients with adverse-risk KMT2A rearrangement, excluding t(9;11), in terms of relapse prevention. [Extracted from the article]

The use of post-transplantation cyclophosphamide (PTCy) for graft-versus-host disease (GVHD) prophylaxis is not established after reduced intensity conditioning (RIC) hematopoietic stem cell transplantation (HSCT) from fully matched donors. This was a randomized, open-label, multicenter, phase 2 trial. All patients received a RIC regimen with fludarabine, intravenous busulfan for 2 days (Flu-Bu2), and a peripheral blood stem cell (PBSC) graft from a matched related or 10/10 HLA-matched unrelated donor. Patients were randomly assigned to receive anti-thymocyte globulin (ATG) 5 mg/kg plus standard GVHD prophylaxis or PTCy 50 mg/kg/d at days +3 and +4 plus standard GVHD prophylaxis. The primary endpoint was the composite endpoint of GVHD- and relapse-free survival (GRFS) at 12 months after HSCT. Eighty-nine patients were randomly assigned to receive either PTCy or control prophylaxis with ATG. At 12 months, disease-free survival was 65.9% in the PTCy group and 67.6% in the ATG group (P = 0.99). Cumulative incidence of relapse, non-relapse mortality, and overall survival were also comparable in the two groups. GRFS at 12 months was 54.5% in the PTCy group versus 43.2% in the ATG group (P = 0.27). The median time to neutrophil and platelet count recovery was significantly longer in the PTCy group compared to the ATG group. Except for day +30, where EORTC QLQ-C30 scores were significantly lower in the PTCy compared to the ATG group, the evolution with time was not different between the two groups. Although the primary objective was not met, PTCy is effective for GVHD prophylaxis in patients receiving Flu-Bu2 conditioning with a PBSC graft from a fully matched donor and was well tolerated in term of adverse events and quality of life. This trial was registered at clinicaltrials.gov: NCT02876679. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to compare two immunosuppressive strategies, based on the use of either rabbit antithymocyte globulin (ATG) or posttransplant cyclophosphamide (PTCY), as a prophylaxis of graft‐versus‐host disease (GVHD) for patients with acute lymphoblastic leukemia (ALL) in first complete remission who underwent hematopoietic cells transplantation from matched unrelated donors. Methods: Overall, 117 and 779 adult patients who received PTCY and ATG, respectively, between the years 2015 and 2020 were included in this retrospective study. The median patient age was 40 and 43 years in the PTCY and ATG groups, respectively, and 37% and 35% of patients, respectively, had Philadelphia chromosome‐positive ALL. Results: In univariate analysis, the cumulative incidence of acute and chronic GVHD did not differ significantly between the study groups. The cumulative incidence of relapse at 2 years was reduced in the PTCY group (18% vs. 25%; p =.046) without a significant impact on nonrelapse mortality (11% vs. 16% in the ATG group; p =.29). The rates of leukemia‐free survival (LFS) and overall survival were 71% versus 59%, respectively (p =.01), and 82% versus 74%, respectively (p =.08). In multivariate analysis, the receipt of ATG compared with PTCY was associated with a reduced risk of extensive chronic GVHD (hazard ratio, 0.54; 95% confidence interval, 0.3–0.98; p =.04) and an increased risk of low LFS (hazard ratio, 1.57; 95% confidence interval, 1.01–2.45; p =.045). Conclusions: The receipt of ATG compared with PTCY, despite the reduced risk of extensive chronic GVHD, is associated with inferior LFS in adults with ALL who undergo hematopoietic cell transplantation from 10/10 human leukocyte antigen‐matched unrelated donors. These findings warrant verification in prospective trials. In this registry‐based study, the authors demonstrate that, for adult patients with acute lymphoblastic leukemia who undergo hematopoietic cell transplantation from 10/10 human leukocyte antigen‐matched unrelated donors, immunosuppression based on posttransplant use of cyclophosphamide is associated with improved leukemia‐free survival compared with protocols that include antithymocyte globulin. These findings suggest preferential use of posttransplant cyclophosphamide in this setting. [ABSTRACT FROM AUTHOR]

Background: Allogeneic hematopoietic cell transplantation (allo‐HCT) is the only cure for acute myeloid leukemia (AML) in second complete remission (CR2). Patients lacking a matched sibling donor (MSD) receive transplants from matched unrelated donors (MUDs), mismatched unrelated donors (MMUDs), haploidentical (haplo) donors, or cord blood. Methods: This is a retrospective, registry‐based European Society for Blood and Marrow Transplantation study that investigates changes in patient‐ and transplant‐related characteristics and posttransplant outcomes over time. Results: We identified 3955 adult patients (46.7% female; median age, 52 years [range, 18–78 years]) with AML in CR2 first transplanted between 2005 and 2019 from a MUD 10/10 (61.4%), MMUD 9/10 (21.9%), or haplo donor (16.7%) and followed for 3.7 years. A total of 725 patients were transplanted between 2005 and 2009, 1600 between 2010 and 2014, and 1630 between 2015 and 2019. Over the three time periods, there was a significant increase in patient age (from 48.7 to 53.5 years; p <.001), use of a haplo donor (from 4.6% to 26.4%; p <.001), and use of posttransplant cyclophosphamide (from 0.4% to 29%; p <.001). There was a significant decrease in total body irradiation and in vivo T‐cell depletion. In multivariate analysis, transplants performed more recently had better outcomes. Leukemia‐free survival (hazard ratio [HR], 0.79; p =.002) and overall survival (HR, 0.73; p <.001) increased over time. Similarly, nonrelapse mortality (HR, 0.64; p <.001) decreased over time. We also observed better graft‐vs‐host disease (GVHD) rates (acute GVHD II–IV: HR, 0.78; p =.03; GVHD‐free, relapse‐free survival: HR, 0.69; p <.001). Conclusions: Even in the absence of an MSD, outcomes of allo‐HCT in CR2 for AML have significantly improved over time, with most favorable outcomes achieved with a MUD. Allogeneic transplantation remains the only curative option for patients with acute myeloid leukemia in second complete remission, with significant changes in patient and transplant characteristics and posttransplant outcomes over time. Even in the absence of matched sibling donors, outcomes have improved over time, with the best outcomes achieved with matched unrelated donors. [ABSTRACT FROM AUTHOR]

Summary: Pre‐transplant measurable residual disease (MRD) predicts relapse and outcome of allogeneic haematopoietic cell transplantation (allo‐HCT). The impact of MRD on the outcomes of post‐transplant cyclophosphamide (PTCy)‐based allo‐HCT from a matched unrelated donor (UD) is unknown. This study assessed the impact of MRD in acute myeloid leukaemia (AML) in the first complete remission (CR1). A total of 272 patients (MRD negative [MRD−], n = 165; MRD positive [MRD+], n = 107) with a median follow‐up of 19 (range: 16–24) months were studied. The incidence of grades II–IV and grades III–IV acute GVHD at day 180 was 25.2% and 25% (p = 0.99), and 10.6% and 6.8% (p = 0.29), respectively, and 2‐year chronic GVHD was 35% and 30.4% (p = 0.96) in MRD+ and MRD− cohorts, respectively. In multivariate analysis, MRD+ status was associated with a higher incidence of relapse (RI) (hazard ratio [HR] = 2.56, 95% CI: 1.39–4.72), lower leukaemia‐free survival (LFS) (HR = 2.04, 95% CI: 1.23–3.39), overall survival (OS) (HR = 1.83, 95% CI: 1.04–3.25) and GVHD‐free, relapse‐free survival (GRFS) (HR = 1.69, 95% CI: 1.10–2.58). MRD status did not have a significant impact on non‐relapse mortality (NRM), or acute or chronic GVHD risk. Among patients with AML undergoing UD allo‐HCT with PTCy, pre‐transplant MRD+ status predicted a higher relapse rate, lower LFS, OS and GRFS. [ABSTRACT FROM AUTHOR]

We compared outcomes of adult patients with secondary acute myeloid leukemia (sAML) versus de novo AML after non-T-depleted haploidentical stem cell transplant (HaploSCT) with post-transplant cyclophosphamide (PTCy). Seventeen hundred and eleven AML patients (sAML-231, de novo-1480) in first complete remission transplanted from 2010 to 2021, were included. Patients with de novo AML were younger, median age 55.8 versus 60.8 years, p < 0.0001, had better transplantation comorbidity index (HCT-CI) ≥ 3 21.3% versus 40.8%, p < 0.0001 and Karnofsky performance status (KPS) with KPS ≥ 90 in 78% versus 68.5%, respectively, p = 0.002. The two patient groups did not differ with respect to gender, cytomegalovirus serostatus, and cell source. Median time from diagnosis to HaploSCT was 5.2 versus 4.9 months, respectively, p = 0.005. Fewer sAML patients received myeloablative conditioning 35.1% versus 50.1%, p < 0.0001. Two hundred and eleven sAML and 410 de novo AML patients were included in the matched-pair analysis matching two de novo AML with each sAML. No significant difference was observed in any transplantation outcome parameter between the sAML versus de novo AML groups. Two-year non-relapse mortality and relapse incidence did not differ with HaploSCT for de novo versus sAML; 21.4% versus 21%, hazard ratio (HR) = 0.98, p = 0.9 and 23.4% versus 20.6%, HR = 0.92, p = 0.67, respectively. Two-year leukemia-free survival, overall survival, and graft-versus-host disease (GVHD)-free, relapse-free survival were also not different between the de novo AML and sAML groups 55.2% versus 58.4%, HR = 0.95, p = 0.67; 61.4% versus 66.4%, HR = 0.91, p = 0.51 and 46.3% versus 48.2%, HR = 0.92, p = 0.48, respectively. Similarly, the incidence of engraftment as well as acute and chronic GVHD was similar between the 2 cohorts. In conclusion, HaploSCT with PTCy may be able to overcome the bad prognosis of sAML as results are not significantly different to those of HaploSCT in de novo AML. [ABSTRACT FROM AUTHOR]

There are situations where non-first-degree (NFD) related donors have to be considered as alternatives to first-degree (FD) related donors for haploidentical hematopoietic cell transplantation (HAPLO). However, the efficacy of these NFD related transplants remains uncertain. All consecutive adult patients (≥ 18 years) with acute myelogenous leukemia (AML) or acute lymphocytic leukemia (ALL) in CR who underwent a first HAPLO between 2010 and 2021 in the European Society for Blood and Marrow Transplantation (EBMT) registry were analyzed. Exact matching and propensity score matching was used. The NFD-to-FD ratio was 1:3. 2703 patients (AML: n = 2047; ALL: n = 656) in CR received a first HAPLO from either NFD (n = 154) or FD (n = 2549) related donors in 177 EBMT centers. 123 NFD and 324 FD HAPLO were included for analysis after matching. Median patient age was 35.6 and 37.2 for the NFD and FD cohorts, respectively. Both cohorts reached good engraftment rates (NFD: 95.7% vs. FD, 95.6%; p = 0.78). The 2-year relapse incidence (NFD, 21.1% vs. FD, 22.6%; p = 0.84) and non-relapse mortality (NRM) (NFD, 13.2% vs. FD, 17.7%; p = 0.33) were not significantly different. The 2-year overall survival (OS) (NFD, 71.8% vs. FD, 68.3%; p = 0.56), leukemia-free survival (LFS) (NFD, 65.7% vs. FD, 59.7%; p = 0.6) and graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS) (NFD, 50.9% vs. FD, 47.8%; p = 0.69) also showed no significant differences. The two cohorts showed no difference in terms of cumulative day 180 grade II-IV, grade III-IV acute GVHD, 2-year cumulative incidences of chronic and extensive chronic GVHD. For HAPLO in patients with acute leukemia, NFD related donors could be equivalent substitutions when FD related donors are not available. [ABSTRACT FROM AUTHOR]

The association between graft-versus-host disease (GVHD) occurrence and acute myeloid leukemia (AML) relapse in patients treated with HLA-haploidentical allogeneic hematopoietic stem cell transplantation (Haplo-HCT) with post-transplant cyclophosphamide (PTCy)-based GVHD prophylaxis has remained debated. Here, we addressed this issue in patients with active AML at transplantation. 2-year cumulative incidences of relapse and leukemia-free survival (LFS) were 49% and 32.3%, respectively. There were no associations between acute nor chronic GVHD of any grade and lower relapse incidence. However, grade I acute GVHD was associated with better LFS (HR = 0.71, 95% CI 0.51–0.99, P = 0.04). In contrast, grade III–IV acute (HR = 3.09, 95% CI 1.87–5.12, P < 0.0001) as well as extensive chronic (HR = 3.3, 95% CI 1.81–6.04, P = 0.0001) GVHD correlated with higher nonrelapse mortality leading to lower LFS (HR = 1.36, 95% CI 0.99–1.86, P = 0.056 and HR = 1.97, 95% CI 1.35–2.89, P = 0.0004, respectively). In conclusion, these data suggest a dissociation of graft-versus-leukemia effects from GVHD in patients with active AML treated with PTCy-based Haplo-HCT. [ABSTRACT FROM AUTHOR]

Background: Achieving complete remission (CR) is the main goal in AML treatment and a prerequisite for successful autologous stem cell transplantation (ACT). Methods: Comparing results of peripheral blood ACT in patients with AML in CR1 attained following 1 versus 2 chemotherapy courses transplanted in 2000–2019. Results: Patients 1532 (84%) with one and 293 (16%) patients with two induction chemotherapies courses (a total of 1825 patients) were included in the study. Follow‐up was 7.9 (95% CI: 7.4–8.4) and 7.7 (95% CI: 7.0–8.6) years (p = 0.8). Time from diagnosis to ACT was 4.7 (range, 3.9–5.8) versus 5.7 (range, 4.7–7.1) months (p < 0.001), respectively. Leukemia free survival (LFS) and overall survival (OS) at 5 years were inferior for patients achieving CR1 with 2 versus 1 course of chemotherapy: 26.6% versus 41.7% (HR = 1.42 [95% CI: 1.22–1.66], p < 0.001) and 36.2% versus 53.3%, (HR = 1.48 [95% CI: 1.25–1.75], p < 0.001), and 5‐year relapse incidence (RI) was higher: 67.2% versus 52.3%, (HR = 1.46 [95% CI: 1.25–1.72], p < 0.001). Five‐year non‐relapse mortality (NRM) was 6.2% versus 6.0% for patients with 2 versus 1 chemotherapy courses, and did not differ significantly (HR = 1.31 [95% CI: 0.81–2.10], p = 0.27). Conclusions: LFS and OS were inferior and relapse rate was higher in AML patients who received two inductions chemotherapy courses to reach CR1 before being autografted. AML patients who required 2 induction courses to achieve remission, may be offered allogeneic transplantation rather than an autologous one in an attempt to reduce their high RI and improve outcomes. [ABSTRACT FROM AUTHOR]

Background: Both mismatched unrelated donor (MMUD) and haploidentical (haplo) transplantation are valid options in patients with high‐risk acute lymphoblastic leukemia (ALL) lacking a matched donor. Methods: The study compared the outcomes of adult patients with ALL in complete remission (CR) who underwent 9/10 MMUD versus haplo transplantation with posttransplant cyclophosphamide (PTCy) as graft‐vs‐host disease (GVHD) prophylaxis in 2010–2020. Results: The study included 781 patients (MMUD, 103; haplo, 678). The median age was 40 (19–73) and 38 (18–75) years, respectively (p =.51). The most frequent immunosuppression agents added to PTCy were mycophenolate mofetil (MMF)/cyclosporine A and MMF/tacrolimus. In vivo T‐cell depletion (anti‐thymocyte globulin) was administered to 21% and 8% of the transplants, respectively (p <.0001). Neutrophil (absolute neutrophil count >0.5 × 109/L) recovery was achieved in 97.1% versus 96.7% versus (p = 1) in MMUD and haplo, respectively. Nonrelapse mortality and relapse incidence were not significantly different between MMUD and haplo, hazard ratio (HR) = 1.45 (95% confidence interval [CI], 0.81–2.62; p =.21) and HR = 0.81 (95% CI, 0.52–1.28, p =.38), respectively. HRs for leukemia‐free survival, overall survival, and GVHD‐free, relapse‐free survival were respectively, HR = 1.05 (95% CI, 0.73–1.50, p =.8), HR = 1.17 (95% CI, 0.77–1.76, p =.46), and HR = 1.07 (95% CI, 0.78–1.46, p =.7) for haplo compared to MMUD. Acute (a)GVHD grade 2–4 was significantly higher with haplo, HR = 1.73 (95% CI, 1.08–2.76, p =.023), whereas aGVHD grade 3–4 and chronic GVHD did not differ significantly between the two transplant groups. Conclusion: Outcomes of MMUD and haplo transplants with PTCy‐based GVHD prophylaxis for ALL patients in CR are similar, apart from a higher incidence of aGVHD with haplo transplants. The outcomes of mismatch unrelated and haploidentical transplants in patients with acute lymphocytic leukemia (ALL) in complete remission are similar. The donor pool for patients with ALL who are in need of allogeneic transplantation and do not have a human leukocyte antigen‐compatible donor is, therefore, enlarged. [ABSTRACT FROM AUTHOR]

Myelodysplastic syndromes (MDS) are the second common indication for an Allo-HCT. We compared the outcomes of 1414 matched sibling (MSD) with 415 haplo-identical donors (HD) transplanted with post-transplant cyclophosphamide (PTCy) as GVHD prophylaxis between 2014 and 2017. The median age at transplant with MSD was 58 and 61 years for HD. The median time to neutrophil engraftment was longer for HD being 20 vs 16 days for MSD (p < 0.001). Two-year overall survival (OS) and PFS (progression free survival) with MSD were significantly better at 58% compared with 50%, p ≤ 0.001, and 51% vs 47%, p = 0.029, with a HD. Relapse at 2 years was lower with a HD 23% than with MSD 29% (p = 0.016). Non relapse mortality (NRM) was higher with HD in the first 6 months post-transplant [HR 2.59 (1.5–4.48) p < 0.001] and was also higher at 2 years being 30% for HD and 20% for MSD, p ≤ 0.001. The incidence of acute GVHD grade II-IV and III–IV at 100 days was comparable for MSD and HD, however, chronic GVHD at 2 years was significantly higher with MSD being 44% vs 32% for HD (p < 0.001). After multivariable analysis, OS and primary graft failure were significantly worse for HD particularly before 6 months [HR 1.93(1.24–3.0)], and HR [3.5(1.5–8.1)]. The median age of HD 37 (IQR 30–47) years was significantly lower than sibling donors 56 (IQR 49–62 years) p < 0.001. However, there was no effect on NRM, relapse or PFS. This data set suggests that a MSD donor remains the preferred choice in MDS over a haplo donor. Transplants with haploidentical donors result in satisfactory long-term outcome, justifying it's use when no better donor is available. [ABSTRACT FROM AUTHOR]

Introduction: The overall outcome of patients with refractory AML (rAML) remains poor. Though allogeneic hematopoietic stem cell transplantation (allo-HSCT) is considered as the only curative therapy, it is routinely recommended only for patients after remission with salvage chemotherapy. Objective: In this study, we evaluated the impact of salvage chemotherapy or allo-HSCT on the overall outcome in rAML. Methods: We collected the clinical data of 220 patients from 4 medical centers and performed retrospective analysis of prognosis factors, including salvage chemotherapy, intensity of chemotherapy, and allo-HSCT. Results: A total of 29 patients received allo-HSCT directly without salvage chemotherapy, 26 patients achieved complete remission (CR) or complete remission with incomplete hematological recovery (CRi) after transplantation and 4-year leukemia-free survival (LFS) and overall survival (OS) were 45.0 ± 10.7 and 51.0 ± 10.6%, respectively. Another 191 patients received salvage chemotherapy and 81 (42.2%) achieved CR or CRi. Thirty-four patients among them underwent subsequent allo-HSCT with 4-year LFS and OS of 46.0 ± 8.8 and 46.2 ± 9.0%. The 4-year LFS and OS in 26 patients who failed to obtain CR or CRi but received allo-HSCT with active disease were 32.9 ± 10.0 and 36.9 ± 10.8%, respectively. For patients who received salvage chemotherapy but not allo-HSCT, few of them became long-term survivors. In multivariate analysis, salvage chemotherapy and the intensity of chemotherapy failed to have significant impact on both OS and LFS. Allo-HSCT was the only prognostic factor for improved OS and LFS in multivariate analysis. Conclusions: These results indicate the benefit of allo-HSCT in patients with rAML and direct allo-HSCT without salvage chemotherapy could be treatment option. [ABSTRACT FROM AUTHOR]

Background: The main goal of this post hoc analysis of the Collaboration to Collect Autologous Transplant Outcomes in Lymphoma and Myeloma (CALM) study was to evaluate the rate of short- and long-term infectious and non-infectious complications occurring after ASCT in patients with multiple myeloma (MM). Methods: The analysis included all patients with MM from the CALM study who underwent ≥1 ASCT. The primary endpoint of the analysis was to determine the rate of infectious and non-infectious complications after ASCT and to compare them in three time periods: 0–100 days, 101 days–1 year, and >1 year after the first transplant. Results: The analysis included a total of 3552 patients followed up for a median of 56.7 months (range 0.4–108.1). Complication rates decreased with the time from ASCT with 24.85 cases per 100 patient-years from day 0 to 100 days after the transplant, and <2.31 cases per 100 patient-years from the 101st day. At 100 days after ASC T, 45.7% of patients had complications, with infectious events being twice as frequent as non-infectious complications. Bacterial infections (6.5 cases per 100 patient-years, 95% CI: 6.1–7.0) and gastrointestinal complications (4.7 cases per 100 patient-years, 95% CI: 4.3–5.1) were the most common early events. The pattern of complications changed with time from ASCT. The presence of complications after ASCT was not associated with overall survival. Conclusions: Our data provide a solid basis for comparing ASCT-related complications to those caused by emerging treatments in multiple myeloma, such as CAR T-cell therapy and other immunotherapies. [ABSTRACT FROM AUTHOR]

Summary: Multiple myeloma (MM) accounts for 10% of haematological malignancies. Overall survival (OS) has improved in recent years due to increased use of autologous stem cell transplantation (ASCT) in the treatment of newly diagnosed MM and the advent of novel agents, including proteasome inhibitors, immunomodulatory drugs and monoclonal antibodies. To assess trends in ASCT including patient selection, choice of induction regimen, depth of response and survival, we performed a retrospective analysis of all patients undergoing first ASCT for MM in European Society for Blood and Marrow Transplantation centres between 1995 and 2019. A total of 117 711 patients across 575 centres were included. The number of transplants performed increased sevenfold across the study period. The median age increased from 55 to 61 years, and the percentage of patients aged >65 years rose from 7% to 30%. Use of chemotherapy‐based induction fell significantly, being largely replaced by bortezomib‐based regimens. The two‐year complete response rate increased from 22% to 42%. The five‐year progression‐free survival and OS rates increased from 28% to 31% and from 52% to 69%, respectively. Transplant mortality fell from 5.9% to 1.5%. Ongoing advances in MM treatment may challenge the future role of ASCT. However, at the current time, ASCT remains central to the MM treatment paradigm. [ABSTRACT FROM AUTHOR]

Nucleophosmin-1 (NPM1) mutations in acute myeloid leukemia (AML) confer a survival advantage in the absence of FLT3-internal tandem duplication (FLT3-ITD). Here, we investigated the main predictors of outcome after allogeneic hematopoietic stem cell transplantation (allo-HCT). We identified 1572 adult (age ≥ 18 year) patients with NPM1-mutated AML in first complete remission (CR1:78%) or second complete remission (CR2:22%) who were transplanted from matched sibling donors (30.8%) or unrelated donors (57.4%) between 2007 and 2019 at EBMT participating centers. Median follow-up for survivors was 23.7 months. FLT3-ITD was present in 69.3% of patients and 39.2% had detectable minimal/measurable residual disease (MRD) at transplant. In multivariate analysis, relapse incidence (RI) and leukemia-free survival (LFS) were negatively affected by concomitant FLT3-ITD mutation (HR 1.66 p = 0.0001, and HR 1.53, p < 0.0001, respectively), MRD positivity at transplant (HR 2.18, p < 10-5 and HR 1.71, p < 10-5, respectively), and transplant in CR2 (HR 1.36, p = 0.026, and HR 1.26, p = 0.033, respectively), but positively affected by Karnofsky score ≥90 (HR 0.74, p = 0.012, and HR 0.7, p = 0.0002, respectively). Overall survival (OS) was also negatively influenced by concomitant FLT3-ITD (HR 1.6, p = 0.0001), MRD positivity at transplant (HR 1.61, p < 10-5), and older age (HR 1.22 per 10 years, p < 0.0001), but positively affected by matched sibling donor (unrelated donor: HR 1.35, p = 0.012; haploidentical donor: HR 1.45, p = 0.037) and Karnofsky score ≥90 (HR 0.73, p = 0.004). These results highlight the independent and significant role of FLT3-ITD, MRD status, and disease status on posttransplant outcomes in patients with NPM1-mutated AML allowing physicians to identify patients at risk of relapse who may benefit from posttransplant prophylactic interventions. [ABSTRACT FROM AUTHOR]

Summary: Allogeneic haematopoietic‐cell transplantation (allo‐HCT) is a potentially curative therapy for high‐risk myelodysplastic syndrome (MDS). Reduced‐intensity conditioning (RIC) is usually associated with lower non‐relapse mortality (NRM), higher relapse rate and similar overall‐survival (OS) as myeloablative‐conditioning (MAC). Fludarabine/treosulfan (FT) is a reduced‐toxicity regimen with intense anti‐leukaemia activity and a favourable toxicity profile. We investigated post‐transplant outcomes in 1722 MDS patients following allo‐HCT with FT (n = 367), RIC (n = 687) or MAC (n = 668). FT and RIC recipients were older than MAC recipients, median age 59, 59 and 51 years, respectively (P < 0·001) but other disease characteristics were similar. The median follow‐up was 64 months (1–171). Five‐year relapse rates were 25% (21–30), 38% (34–42) and 25% (22–29), after FT, RIC and MAC, respectively, (P < 0·001). NRM was 30% (25–35), 27% (23–30) and 34% (31–38, P = 0·008), respectively. Five‐year OS was 50% (44–55), 43% (38–47), and 43% (39–47), respectively (P = 0·03). In multivariate analysis, FT was associated with a lower risk of relapse (HR 0·55, P < 0·001) and better OS (HR 0·72, P = 0·01). MAC was associated with higher NRM (HR 1·44, P = 0·001). In conclusion, FT is associated with similar low relapse rates as MAC and similar low NRM as RIC, resulting in improved OS. FT may be the preferred regimen for allo‐HCT in MDS. [ABSTRACT FROM AUTHOR]

NK cells are innate immune cells with inherent capabilities in both recognizing and killing cancer cells. NK cell phenotypes and functional alterations are being described with increasing precision among patients harboring various cancer types, emphasizing the critical role that NK cells play in antitumor immune responses. In addition, advances in understanding NK cell biology have improved our knowledge of such alterations, thereby expanding the potential exploitation of NK cells' anticancer capabilities. In this review, we present an overview of (1) the various types of NK cell alterations that may contribute to immune evasion in cancer patients and (2) the various strategies to improve NK cell‐based anticancer immunotherapies, including pharmacologic modulation and/or genetic modification. [ABSTRACT FROM AUTHOR]

Background: Allogeneic hematopoietic cell transplantation (allo-HCT) using a mismatched unrelated donor (MMUD) and cord blood transplantation (CBT) are valid alternatives for patients without a fully human leukocyte antigen (HLA)-matched donor. Here, we compared the allo-HCT outcomes of CBT versus single-allele-mismatched MMUD allo-HCT with post-transplant cyclophosphamide (PTCy) in acute myeloid leukemia. Methods: Patients who underwent a first CBT without PTCy (N = 902) or allo-HCT from a (HLA 9/10) MMUD with PTCy (N = 280) were included in the study. A multivariate regression analysis was performed for the whole population. A matched-pair analysis was carried out by propensity score-based 1:1 matching of patients (177 pairs) with known cytogenetic risk. Results: The incidence of grade II–IV and grade III–IV acute graft-versus-host disease (GVHD) at 6 months was 36% versus 32% (p = 0.07) and 15% versus 11% (p = 0.16) for CBT and MMUD cohorts, respectively. CBT was associated with a higher incidence of graft failure (11% vs. 4%, p < 0.01) and higher 2-year non-relapse mortality (NRM) (30% vs. 16%, p < 0.01) compared to MMUD. In the multivariate analysis, CBT was associated with a higher risk of, NRM (HR = 2.09, 95% CI 1.46–2.99, p < 0.0001), and relapse (HR = 1.35, 95% CI 1–1.83, p = 0.05), which resulted in worse leukemia-free survival (LFS) (HR = 1.68, 95% CI 1.34–2.12, p < 0.0001), overall survival (OS) (HR = 1.7, 95% CI 1.33–2.17, p < 0.0001), and GVHD-free, relapse-free survival (GRFS) (HR = 1.49, 95% CI 1.21–1.83, p < 0.0001) compared to MMUD. The risk of grade II–IV acute GVHD (p = 0.052) and chronic GVHD (p = 0.69) did not differ significantly between the cohorts. These results were confirmed in a matched-pair analysis. Conclusions: CBT was associated with lower LFS, OS, and GRFS due to higher NRM, compared to MMUD allo-HCT with PTCy. In the absence of a fully matched donor, 9/10 MMUD with PTCy may be preferred over CBT. [ABSTRACT FROM AUTHOR]

Background: In autologous stem cell transplant (ASCT)‐eligible myeloma patients, prolonged induction does not necessarily improve the depth of response. Method: We analyzed 1222 ASCT patients who were classified based on (a) the interval between induction and stem cell collection, (b) the type of induction regimen: BID (Bortezomib, IMiDs, and Dexamethasone), Bortezomib‐based, or CTD (Cyclophosphamide, Thalidomide, and Dexamethasone), and (c) the time to best response (Early ie, best response within 4 or 5 months, depending on the regimen vs Late; Good ie, VGPR or better vs Poor). Results: The length of induction treatment required to achieve a Good response did not affect PFS (P =.65) or OS (P =.61) post‐ASCT. The three types of regimen resulted in similar outcomes: median PFS 31, 27.7 and 30.8 months (P =.31), and median OS 81.7, 92.7, and 77.4 months, respectively (P =.83). On multivariate analysis, neither the type nor the duration of the induction regimen affected OS and PFS, except for Early Good Responders who had a better PFS compared to Early Poor Responders (HR = 1.21, P‐value =.02). However, achieving a Good response at induction was associated with a better response (≥VGPR) post‐transplant. Conclusion: The kinetics of response did not affect outcomes. [ABSTRACT FROM AUTHOR]

Summary: Optimal donor choice for a second allogeneic haematopoietic cell transplant (allo‐HCT) in relapsed acute myeloid leukaemia (AML) remains unknown. We compared overall survival (OS) using registry data from the Acute Leukemia Working Party (ALWP) of the European Society for Blood and Marrow Transplantation (EBMT) involving 455 adults who received a second allo‐HCT from a human leucocyte antigen (HLA)‐matched unrelated (MUD) (n = 320) or a haploidentical (n = 135) donor. Eligibility criteria required adults aged ≥18 years who received a second allo‐HCT for treating AML relapse between 2005 and 2019. The primary end‐point was OS. There was no statistically significant difference in the median (interquartile range) age between the groups, MUD 46 (35–58) versus haploidentical 44 (33–53) years (P = 0·07). The median OS was not different between the MUD and the haploidentical groups (10 vs. 11 months, P = 0·57). Similarly, the 2‐year OS was 31% for the MUD and 29% for the haploidentical donor groups. The OS was worse if the procedure was performed with active AML [hazard ratio (HR) 1·42, 95% confidence interval (CI) 1·07–1·89; P = 0·02]. Conversely, a longer time from first allo‐HCT to relapse (>13·2 months) was associated with better OS (HR 0·50, 95% CI 0·37–0·69; P < 0·0001). The results of the present analysis limit the ability to recommend one donor type over another when considering a second allo‐HCT for relapsed AML. Our findings highlight that best OS is achieved when receiving the second allo‐HCT in complete remission. [ABSTRACT FROM AUTHOR]

Rituximab (R) is increasingly incorporated in reduced intensity conditioning (RIC) regimens for allogeneic hematopoietic cell transplantation (alloHCT) in patients with B-cell malignancies, not only to improve disease control, but also to prevent graft-versus-host disease (GVHD). There are no randomized prospective data to validate this practice, although single center data and the CIBMTR analysis have shown promising results. We aimed at validation of these findings in a large registry study. We conducted a retrospective analysis using the EBMT registry of 3,803 adult patients with B-cell malignancies undergoing alloHCT (2001–2013) with either rituximab (R-RIC-9%) or non-rituximab (RIC-91%) reduced intensity regimens respectively. Median age and median follow up were 55 years (range 19.1–77.3) and 43.2 months (range 0.3–179.8), respectively. There was no difference in transplant outcomes (R-RIC vs RIC), including 1-year overall survival (69.9% vs 70.7%), 1-year disease-free survival (64.4% vs 62.2%), 1-year non-relapse mortality (21% vs 22%), and day-100 incidence of acute GVHD 2-4° (12% vs 12%). In summary, we found that addition of rituximab in RIC regimens for B-cell malignancies had no significant impact on major transplant outcome variables. Of note, data on chronic GVHD was not available, limiting the conclusions that can be drawn from the present study. [ABSTRACT FROM AUTHOR]

BACKGROUND: Graft‐versus‐host disease (GVHD) is a major complication after allogeneic hematopoietic stem cell transplantation (allo‐HSCT). Addition of antithymocyte globulin (ATG) or post‐transplantation cyclophosphamide (PTCY) to standard immunosuppressive agents reduces GVHD in different donor settings. METHODS: We compared the outcomes of adults with acute myeloid leukemia undergoing allo‐HSCT from HLA‐identical sibling donors after the use of PTCY (n = 197) or ATG (n = 1913). RESULTS: Patients in the PTCY group were younger than those in the ATG group (median age, 47 vs 54 years; P <.01). Peripheral blood was the most frequently used stem cell source, being significantly more frequent in the ATG group than in the PTCY group (95% vs 70% P <.01). The conditioning regimen was more frequently myeloablative in the PTCY group than in the ATG group (59% vs 48%; P <.01). Time to neutrophil engraftment was shorter in the ATG group than in the PTCY group (17 vs 20 days; P <.01). No differences were observed according to the other transplantation outcomes, except for chronic GVHD of all grades and extensive chronic GVHD at 2 years, which were significantly lower in the ATG group compared with the PTCY group (P <.02). CONCLUSION: PTCY is feasible in an HLA‐identical sibling setting, and despite similar outcomes, ATG may be associated with lower incidence of chronic GVHD. Addition of antithymocyte globulin (ATG) or post‐transplantation cyclophosphamide (PTCY) to standard immunosuppressive agents in patients who received a transplant from an HLA‐identical sibling donor is feasible and allows low rates of graft‐versus‐host disease (GVHD).When compared with PTCY, the use of ATG is associated with lower cumulative incidence of chronic GVHD. [ABSTRACT FROM AUTHOR]

Limited data are currently available on the outcome of patients with acute myeloid leukemia (AML) undergoing allogeneic stem cell transplantation (allo‐SCT) with a reduced performance status. We herein present the results of a registry study on 2,936 AML patients undergoing allo‐SCT in first remission (CR1) with a Karnofsky Performance Status (KPS) score less than or equal to 80%. Two‐year leukemia‐free survival (LFS), overall survival (OS) and graft‐versus‐host disease (GVHD)‐free, and relapse‐free survival (GRFS) rates were 54%, 59%, and 41%, respectively. In multivariable analysis, patients with a KPS score = 80% had lower non‐relapse mortality (NRM) and superior OS in comparison to patients with a KPS score <80% (p < 0.001). In the subgroup of patients with a KPS score =80%, a reduced‐intensity conditioning (RIC) regimen was associated with an increased risk of relapse (p = 0.002) and lower GRFS (p < 0.001) compared to myeloablative conditioning (MAC). Differently, in patients with a KPS score <80%, a RIC regimen resulted in lower NRM (p < 0.001), whereas relapse incidence did not differ, thus leading to an improved GRFS (p = 0.008) as compared to MAC. A transplant from a matched sibling donor (MSD) was associated with a reduced incidence of grade III‐IV acute GVHD (p < 0.01) and NRM (p < 0.01) in comparison to other donor types. In conclusion, allo‐SCT appears feasible in AML patients with a jeopardized KPS score. Survival is significantly affected by the conditioning intensity, which should be adjusted according to the severity of KPS impairment. [ABSTRACT FROM AUTHOR]

Reference 1 Nagler A. Non-T-depleted haploidentical transplantation with post-transplant cyclophosphamide in patients with secondary versus de novo AML in first complete remission: a study from the ALWP/EBMT. The correct affiliation can be viewed ahead in this Correction article: SP 7 sp Transplantation Unit Department of Oncology and Haematology, IRCCS Humanitas Research Hospital, Milan, Italy. [Extracted from the article]

Objective: Recipients of allogeneic hematopoietic stem cell transplantation (allo‐HCT) with positive cytomegalovirus (CMV) serology are at increased risk of morbidity and mortality. The primary objective of this study was to assess the association between treated CMV infection and overall mortality within 1 year after allo‐HCT in adult CMV‐seropositive Recipients (R+). Secondary objectives included overall 5‐year mortality after allo‐HCT, risk factors for treated CMV infection, associations between treated CMV infection and allo‐HCT complications and medical costs. Methods: A multicenter retrospective cohort study was conducted in adult CMV‐seropositive recipients (R+) who underwent to allo‐HCT between 1st January 2010 and 31st December 2014. Results: Five hundred seventy two CMV‐seropositive patients (mean age, 50.2 years) undergoing allo‐HCT between 2010 and 2014 were included; 55.9% of donors were CMV seropositive. CMV infection treated with antiviral therapy was reported in 227 patients (39.7%) after transplantation. One‐year overall mortality was significantly increased in patients with treated CMV infections (hazard ratio, 1.86; 95% CI, 1.16‐3.00; P =.011). Mean medical costs during the first post‐HCT year were higher in patients with CMV infection (€46 853 vs €31 318; P <.0001). Conclusion: In this large cohort of CMV‐seropositive patients undergoing allo‐HCT, treated CMV infection was significantly associated with an increased 1‐year risk of overall mortality, with increased length of stay and with hospitalization cost. The burden of CMV disease in allo‐HCT could be reduced in the future by appropriate prophylactic strategies. [ABSTRACT FROM AUTHOR]

Allogeneic stem cell transplantation (allo-SCT) represents the most beneficial treatment for patients with active relapsed/refractory (R/R) hematologic malignancies. Recently, sequential regimens combining debulking chemotherapy followed by reduced-intensity conditioning (RIC) have shown encouraging results for these patients. In this retrospective study, we report the extended results of a sequential regimen of clofarabine, cytosine arabinoside, and RIC in 131 adults with active R/R myeloid disease at transplant. Conditioning consisted of clofarabine (30 mg/m2/day) and cytosine arabinoside (1 g/m2/day) for 5 days, followed, after a rest of 3 days, by an RIC combining cyclophosphamide (60 mg/kg) for 1 day, iv busulfan (3.2 mg/kg/day) for 2 days, and anti-thymocyte globulin (2.5 mg/kg/day) for 2 days. Between 2007 and 2016, 131 patients (males n = 75, median age: 52.6 years) were identified from the SFGM-TC registry. There were 111 acute myeloid leukemia (AML) patients and 20 cases with myelodysplastic or myeloproliferative syndrome. Status at transplant was known for all but 4 patients and was primary refractory (n = 81) and 1st or 2nd relapse (n = 46). All patients received allo-SCT from a matched donor (sibling n = 64, unrelated n = 67). Engraftment was observed in 105/122 (86%) evaluable cases and 63% of the patients achieved complete remission (CR) after transplant. The 1-year overall survival, disease-free survival, relapse incidence, non-relapse mortality, and graft-versus-host disease-free/relapse-free survival were 39.2%, 28.1%, 41.0%, 30.8%, and 22.2%, respectively. This study confirms that this sequential clofarabine-based regimen provides a high CR rate in this critical population, although relapse remains a matter of concern. [ABSTRACT FROM AUTHOR]

Acute graft-vs.-host disease (aGvHD) is one of the most frequent causes of transplant-related mortality (TRM) after allogeneic hematopoietic cell transplantation (alloHCT). Its treatment is complex and costly. The aim of this study was to retrospectively analyze the impact of country-specific socioeconomic factors on outcome of patients who experience severe aGvHD. Adults with hematological malignancies receiving alloHCT from either HLA-matched siblings (n = 1,328) or unrelated donors (n = 2,824) developing grade 3 or 4 aGvHD were included. In univariate analysis, the probability of TRM at 2 years was increased for countries with lower current Health Care Expenditure (HCE, p = 0.04), lower HCE as % of Gross Domestic Product per capita (p = 0.003) and lower values of the Human Development Index (p = 0.02). In a multivariate model, the risk of TRM was most strongly predicted by current HCE (HR = 0.76, p = 0.006). HCE >median was also associated with reduced risk of the overall mortality (HR 0.73, p = 0.0006) and reduced risk of treatment failure (either relapse or TRM; HR 0.77, p = 0.004). We conclude that country-specific socioeconomic factors, in particular current HCE, are strongly associated with survival of patients who experience severe aGvHD. [ABSTRACT FROM AUTHOR]

Background: 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. [ABSTRACT FROM AUTHOR]

Background: Peripheral T cell lymphomas form a heterogeneous group with a usually dismal prognostic. The place of allogeneic stem cell transplantation to treat PTCL is debated. Methods: We retrospectively analyzed the overall survival (OS), event-free survival (EFS), relapse, and transplant-related mortality (TRM) and associated variables in 285 adults with non-primary cutaneous PTCL (PCTL-NOS (39%), angioimmunoblastic T cell lymphomas (29%), anaplastic T cell lymphomas (15%), and other subtypes (17%)), who received alloSCT in 34 centers between 2006 and 2014. Results: AlloSCT was given as part of front-line therapy (n = 138) to 93 patients in first complete response (CR) and 45 in first partial response (PR), and of salvage therapy (n = 147) to 116 patients for second or more CR/PR and 31 for progressive disease. Reduced-intensity conditioning (RIC) was given to 172 patients (62%), while 107 (38%) received myeloablative conditioning (MAC). The median follow-up was 72.4 months. The 2- and 4-year OS were 65% and 59%, respectively, and the cumulative incidence of relapse was 18% after 1 year and 19% after 2 years. TRM was 21% at 1 year, 24% after 2 years, and 28% after 4 years. In multivariate analysis, grade III–IV acute GvHD (HR = 2.57, 95% CI 1.53–4.31; p = 0.00036), low Karnofsky score < 80% (HR = 5.14, 95% CI 2.02–13.06; p = 0.00058), and progressive disease status before transplant (HR = 2.21, 95% CI 1.25–3.89; p = 0.0062) were significantly associated with a reduced OS. Conclusions: The data demonstrate in the largest retrospective cohort of non-cutaneous PTCL so far reported that alloSCT after RIC or MAC is an effective strategy, even in chemoresistant patients. [ABSTRACT FROM AUTHOR]

Background: The use of post-transplant cyclophosphamide (PTCy) is highly effective in preventing graft-versus-host disease (GVHD) in the haploidentical (Haplo) transplant setting and is being increasingly used in matched sibling (MSD) and matched unrelated (MUD) transplants. There is no information on the impact of donor types using homogeneous prophylaxis with PTCy. Methods: We retrospectively compared outcomes of adult patients with acute myeloid leukemia (AML) in first complete remission (CR1) who received a first allogeneic stem cell transplantation (SCT) with PTCy as GVHD prophylaxis from MSD (n = 215), MUD (n = 235), and Haplo (n = 789) donors registered in the EBMT database between 2010 and 2017. Results: The median follow-up was 2 years. Haplo-SCT carried a significantly increased risk of acute grade II–IV GVHD (HR 1.6; 95% CI 1.1–2.4) and NRM (HR 2.6; 95% CI 1.5–4.5) but a lower risk of relapse (HR 0.7; 95% CI 0.5–0.9) that translated to no differences in LFS (HR 1.1; 95% CI 0.8–1.4) or GVHD/relapse-free survival (HR 1; 95% CI 0.8–1.3). Interestingly, the use of peripheral blood was associated with an increased risk of acute (HR 1.9; 95% CI 1.4–2.6) and chronic GVHD (HR 1.7; 95% CI 1.2–2.4) but a lower risk of relapse (HR 0.7; 95% CI 0.5–0.9). Conclusions: The use of PTCy in patients with AML in CR1 receiving SCT from MSD, MUD, and Haplo is safe and effective. Haplo-SCT had increased risk of acute GVHD and NRM and lower relapse incidence but no significant difference in survival. [ABSTRACT FROM AUTHOR]

We studied a cohort of 367 healthy related donors who volunteered to donate their hematopoietic stem cells for allogeneic transplantation. All donors were homogeneously cared for at a single institution, and received rhG-CSF as a mobilization treatment prior to undergoing apheresis. Peripheral blood CD34+ cell counts were used as the main surrogate marker for rhG-CSF induced mobilization. We searched whether inter-individual variations in known genetic polymorphisms located in genes whose products are functionally important for mobilization, could affect the extent of CD34+ mobilization, either individually or in combination. We found little or no influence of individual SNPs or haplotypes for the SDF1, CXCR4, VCAM and VLA4 genes, whether using CD34+ cell counts as a continuous or a categorical variable. Simple clinical characteristics describing donors such as body mass index, age and possibly sex are more potent predictors of stem cell mobilization. The size of our cohort remains relatively small for genetic analyses, however compares favorably with cohorts analyzed in previously published reports suggesting associations of genetic traits to response to rhG-CSF; notwithstanding this limitation, our data do not support the use of genetic analyses when the choice exists of several potential donors for a given patient. [ABSTRACT FROM AUTHOR]

Following chemotherapy, secondary acute myeloid leukemia (sAML), occurring after antecedent hematologic diseases, previous chemotherapy or radiation, has an inferior prognosis compared with de novo AML. To define the outcome of sAML in the context of allogeneic stem cell transplantation (alloSCT), a retrospective, registry-based comparison was performed, including 11,439 patients with de novo and 1325 with sAML. Among transplants in first complete remission (CR1) (n = 8,600), the 3-year cumulative incidence of relapse (RI) and non-relapse mortality (NRM) was 28.5% and 16.4% for de novo, and 35% and 23.4% for sAML. Three-year overall survival (OS), leukemia-free survival (LFS) and Graft-versus-Host Disease/relapse-free survival (GRFS) was 60.8%, 55.1%, and 38.6% for de novo, and 46.7%, 41.6%, and 28.4% for sAML, respectively. In multivariate analysis, sAML was associated with a lower OS (HR = 1.33 [95% CI = 1.21–1.48]; p < 10−5), LFS (HR = 1.32 [95% CI = 1.19–1.45]; p < 10−5) and GRFS (HR = 1.2 [95% CI = 1.1–1.31]; p < 10−4) and higher NRM (HR = 1.37 [95% CI = 1.17–1.59]; p < 10−4) and RI (HR = 1.27 [95% CI = 1.12–1.44]; p < 10−3). Results of the Cox model were confirmed in a matched-pair analysis. In contrast, results did not differ between de novo and sAML after alloSCT in induction failure or relapse. Hence, this analysis identified sAML as an independent risk factor for outcome after alloSCT in CR1. [ABSTRACT FROM AUTHOR]