Phase II Trial of Graft-versus-Host Disease Prophylaxis with Post-Transplantation Cyclophosphamide after Reduced-Intensity Busulfan/Fludarabine Conditioning for Hematological Malignancies

• Published in: Biology of blood and marrow transplantation 2015-05, Vol.21 (5), p.906-912
• Main Authors: Alousi, Amin M, Brammer, Jonathan E, Saliba, Rima M, Andersson, Borje, Popat, Uday, Hosing, Chitra, Jones, Roy, Shpall, Elizabeth J, Khouri, Issa, Qazilbash, Muzaffar, Nieto, Yago, Shah, Nina, Ahmed, Sairah, Oran, Betul, Al Atrash, Gheath, Ciurea, Stefan, Kebriaei, Partow, Chen, Julianne, Rondon, Gabriela, Champlin, Richard E
• Format: Article
• Language: English
• Subjects: Acute; Adolescent; Adult; Aged; Allografts; Busulfan - administration & dosage; Child; Child, Preschool; Chronic; Cyclophosphamide - administration & dosage; Disease-Free Survival; Female; Graft vs Host Disease - mortality; Graft vs Host Disease - prevention & control; Graft-versus-host disease; Hematologic Neoplasms - mortality; Hematologic Neoplasms - therapy; Hematology, Oncology and Palliative Medicine; Hematopoietic Stem Cell Transplantation; Humans; Infant; Male; Marrow; Middle Aged; Prospective Studies; Stem cell transplantation; Survival Rate; Transplantation Conditioning; Vidarabine - administration & dosage; Vidarabine - analogs & derivatives
• ISSN: 1083-8791; 1523-6536
• DOI: 10.1016/j.bbmt.2015.01.026

Abstract Graft-versus-host disease (GVHD) prophylaxis with post-transplantation cyclophosphamide (CY) after ablative HLA-matched bone marrow (BM) transplantation has been reported to have comparable rates of acute GVHD with an apparent reduction in chronic GVHD and infections when compared to historical prophylaxis with a calcineurin-inhibitor (CNI) and methotrexate (MTX). We conducted a phase II trial of post-transplantation CY (post-CY) after reduced-intensity conditioning (RIC) using intravenous busulfan (area under the curve of 4000 micromolar minute), fludarabine (40 mg/m2 ) for 4 days, and CY 50 mg/kg on days +3 and +4 after BM or peripheral blood (PB) transplantations from matched related (MRD) or unrelated donors (MUD). MUD recipients received antithymocyte globulin (ATG); however, a later amendment removed ATG. Forty-nine patients were treated (acute myeloid leukemia/myelodysplastic syndrome, 82%). Median age was 62 years (range, 39 to 72). Fifteen patients received an MRD (9 PB/6 BM); 34 had a MUD (2 PB/32 BM). The cumulative incidence of grade II to IV acute GVHD, III to IV acute GVHD, and chronic GVHD was 58%, 22%, and 18%, respectively. A matched cohort analysis compared outcomes to tacrolimus/methotrexate GVHD prophylaxis and indicated higher rates of acute GVHD grade II to IV (46% versus 19%; hazard ratio [HR], 2.8; P  = .02) and treatment-related mortality (HR, 3.3; P  = .035) and worse overall survival (HR, 1.9; P  = .04) with post-CY. The incidence of chronic GVHD and CMV reactivation did not differ. This study suggests that post-CY should not be used as sole GVHD prophylaxis after a RIC transplantation from HLA-matched donors.