FLAMSA-Busulfan-Melphalan as a Sequential Conditioning Regimen in HLA-Matched or Haploidentical Hematopoietic Stem Cell Transplantation for High-Risk Myeloid Diseases.

Abstract Background Given the poor prognosis of relapsed/refractory myeloid malignancies, the concept of sequential conditioning prior to allogeneic hematopoietic stem cell transplantation has been shown as an effective approach. Objective We sought to evaluate a sequential scheme combining fludarabine, amsacrine and cytarabine for cytoreduction, followed by a reduced-intensity conditioning with melphalan and busulfan (FLAMSA-BuMel), which was designed to be suitable for both HLA-matched and haploidentical grafts. Study design In this monocentric retrospective study, 36 adult patients with high-risk myeloid malignancies were included, and transplanted from HLA-matched (n=19) or haploidentical (n=17) donors. Along with the standard prophylaxis of graft-versus-host disease (GvHD), patients with HLA-haploidentical donor received post-transplant high-dose cyclophosphamide. A post-transplant consolidation treatment with low-dose 5-azacytidine and prophylactic donor lymphocyte infusions was associated, whenever possible. Results Thirty patients (83%) achieved complete remission at day +30. With a median follow-up of 30.0 months, the 2-year overall survival was 89% in the HLA-matched group, versus 34% in the HLA-haploidentical group (P=.0018). In these groups, the 2-year disease-free survival was 68% and 34% respectively (P=.013). At 2 years, probability of relapse was 32% and 20%, while non-relapse mortality was 0% and 58% respectively (P=.0003). The leading cause of death was relapse in the HLA-matched group (3/19), and hemorrhagic events (5/17) in the HLA-haploidentical group, favoured by significantly delayed platelet reconstitution and a severe GvHD context. Conclusion These data confirm the feasibility of FLAMSA-BuMel as a sequential conditioning for the treatment of high-risk myeloid malignancies. Further use of bone marrow as preferred graft source might reduce the incidence of acute GvHD and non-relapse mortality in haploidentical setting.