Busulfan-fludarabine versus busulfan-cyclophosphamide for allogeneic transplant in acute myeloid leukemia: long term analysis of GITMO AML-R2 trial.

We report the long-term results of a randomized trial (GITMO, AML-R2), comparing 1:1 the combination of busulfan and cyclophosphamide (BuCy2, n = 125) and the combination of busulfan and fludarabine (BuFlu, n = 127) as conditioning regimen in acute myeloid leukemia patients (median age 51 years, range 40-65) undergoing allogeneic hematopoietic stem cell transplantation. With a median follow-up of 6 years, significantly better non-relapse mortality (NRM) was confirmed in BuFlu recipients, which is sustained up to 4 years after transplant (10% vs. 20%, p = 0.0388). This difference was higher in patients older than 51 years (11% in BuFlu vs. 27% in BuCy2, p = 0.0262). The cumulative incidence of relapse, which was the first cause of death in the entire study population, did not differ between the two randomized arms. Similarly, the leukemia-free survival (LFS) and overall survival (OS) were not different in the two cohorts, even when stratifying patients per median age. Graft-and relapse-free survival (GRFS) in BuFlu arm vs. the BuCy2 arm was 25% vs. 20% at 4 years and 20% vs. 17% at 10 years. Hence, the benefit gained by NRM reduction is not offsets by an increased relapse. Leukemia relapse remains a major concern, urging the development of new therapeutic approaches.

Myelofibrosis and allogeneic transplantation: critical points and challenges.

New available drugs allow better control of systemic symptoms associated with myelofibrosis (MF) and splenomegaly but they do not modify the natural history of progressive and poor prognosis disease. Thus, hematopoietic stem cell transplantation (HSCT) is still considered the only available curative treatment for patients with MF. Despite the increasing number of procedures worldwide in recent years, HSCT for MF patients remains challenging. An increasingly complex network of the patient, disease, and transplant-related factors should be considered to understand the need for and the benefits of the procedure. Unfortunately, prospective trials are often lacking in this setting, making an evidence-based decision process particularly arduous. In the present review, we will analyze the main controversial points of allogeneic transplantation in MF, that is, the development of more sophisticated models for the identification of eligible patients; the need for tools offering a more precise definition of expected outcomes combining comorbidity assessment and factors related to the procedure; the decision-making process about the best transplantation time; the evaluation of the most appropriate platform for curative treatment; the impact of splenomegaly; and splenectomy on outcomes.

Posttransplant cyclophosphamide versus anti-thymocyte globulin versus combination for graft-versus-host disease prevention in haploidentical transplantation for adult acute myeloid leukemia: A report from the European Society for Blood and Marrow Transplantation Acute Leukemia Working Party.

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.