title: Phase II Trial of Graft-versus-Host Disease Prophylaxis with Post-Transplantation Cyclophosphamide after Reduced-Intensity Busulfan/Fludarabine Conditioning for Hematological Malignancies.
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/m(2)) 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.
authors: Department of Stem Cell Transplantation and Cellular Therapies, University of Texas MD Anderson Cancer Center, Houston, Texas. Electronic address: aalousi@mdanderson.org.
authors: Amin M
authors: AM
authors: Alousi
authors: Department of Stem Cell Transplantation and Cellular Therapies, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Jonathan E
authors: JE
authors: Brammer
authors: Department of Stem Cell Transplantation and Cellular Therapies, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Rima M
authors: RM
authors: Saliba
authors: Department of Stem Cell Transplantation and Cellular Therapies, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Borje
authors: B
authors: Andersson
authors: Department of Stem Cell Transplantation and Cellular Therapies, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Uday
authors: U
authors: Popat
authors: Department of Stem Cell Transplantation and Cellular Therapies, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Chitra
authors: C
authors: Hosing
authors: Department of Stem Cell Transplantation and Cellular Therapies, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Roy
authors: R
authors: Jones
authors: Department of Stem Cell Transplantation and Cellular Therapies, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Elizabeth J
authors: EJ
authors: Shpall
authors: Department of Stem Cell Transplantation and Cellular Therapies, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Issa
authors: I
authors: Khouri
authors: Department of Stem Cell Transplantation and Cellular Therapies, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Muzaffar
authors: M
authors: Qazilbash
authors: Department of Stem Cell Transplantation and Cellular Therapies, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Yago
authors: Y
authors: Nieto
authors: Department of Stem Cell Transplantation and Cellular Therapies, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Nina
authors: N
authors: Shah
authors: Department of Stem Cell Transplantation and Cellular Therapies, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Sairah
authors: S
authors: Ahmed
authors: Department of Stem Cell Transplantation and Cellular Therapies, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Betul
authors: B
authors: Oran
authors: Department of Stem Cell Transplantation and Cellular Therapies, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Gheath
authors: G
authors: Al Atrash
authors: Department of Stem Cell Transplantation and Cellular Therapies, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Stefan
authors: S
authors: Ciurea
authors: Department of Stem Cell Transplantation and Cellular Therapies, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Partow
authors: P
authors: Kebriaei
authors: Department of Stem Cell Transplantation and Cellular Therapies, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Julianne
authors: J
authors: Chen
authors: Department of Stem Cell Transplantation and Cellular Therapies, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Gabriela
authors: G
authors: Rondon
authors: Department of Stem Cell Transplantation and Cellular Therapies, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Richard E
authors: RE
authors: Champlin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D064591:Allografts; D002066:Busulfan / Q000008:administration & dosage*; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000008:administration & dosage*; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease / Q000401:mortality / Q000517:prevention & control; D019337:Hematologic Neoplasms / Q000401:mortality / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D015996:Survival Rate; D019172:Transplantation Conditioning; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D003520:Cyclophosphamide; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine
keywords: Acute; Chronic; Graft-versus-host disease; Marrow; Stem cell transplantation