Posttransplant cyclophosphamide‐based anti–graft‐vs‐host disease prophylaxis in patients with acute lymphoblastic leukemia treated in complete remission with allogeneic hematopoietic cell transplantation from human leukocyte antigen‐mismatched unrelated donors versus haploidentical donors: A study on behalf of the ALWP of the EBMT

Abstract

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 × 10 9 /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)

Mafosfamide, a cyclophosphamide analog, causes a proinflammatory response and increased permeability on endothelial cells in vitro

“…Endothelial cell activation and damage may be due to different factors, such as the conditioning regimens, cytokines and chemokines produced by the injured tissues, the engraftment itself, the allogenicity, and also some drugs used during the transplant procedure, like granulocyte colonystimulating factor (G-CSF) (18) and immunosuppressant therapies (19,20). Cyclosporine A (CSA) is an immunosuppressive drug used as the standard GVHD prophylaxis in allo-HCT (21). However, it has been demonstrated that CSA has a clear adverse effect on the endothelium (19,22,23).…”