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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]

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]

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Purpose: Acute myeloid leukemia (AML) is a disease of older patients. Progress in allogeneic hematopoietic cell transplantation (allo-HCT) allowed the delivery of allo-HCT to older patients. We assessed changes over time in transplant characteristics and outcomes in patients with AML ages 65 years and above., Patients and Methods: We identified 7,215 patients with AML (median age 68 years, range 65-80) allografted between 2000 and 2021 in first complete remission (CR1; 64%), second or subsequent remission (CR2+; 14%), or active disease (22%)., Results: Median follow-up was 40 months. The 3-year cumulative relapse incidence (RI) gradually and significantly decreased from 37% to 31%, then to 30% (P = 0.001) over the three time periods (2000-2009; 2010-2014; 2015-2021), whereas nonrelapse mortality (NRM) decreased from 31% and 31% to 27% (P = 0.003). The 3-year leukemia-free survival (LFS) and overall survival (OS) gradually and significantly improved from 32% to 38%, and then to 44% (P = 0.001) and from 37% to 42%, and then to 49% (P = 0.001), respectively. In multivariate analysis, significant improvement in the RI, LFS, and OS were noted after 2015, whereas NRM was not significantly affected. This improvement was observed regardless of disease status at transplant., Conclusions: In older patients with AML, we observed an impressive improvement over time in posttransplant outcomes, mostly attributed to decreased RI rather than decreased NRM, and regardless of disease status at transplant. These large-scale, real-world data can serve as a benchmark for future studies in this setting and indicate that the opportunity for transplant for the elderly should be mandatory and no longer an option., (©2024 American Association for Cancer Research.)