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Clinical Trial
. 2015 May;21(5):906-12.
doi: 10.1016/j.bbmt.2015.01.026. Epub 2015 Feb 7.

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

Amin M Alousi  1 , Jonathan E Brammer  2 , Rima M Saliba  2 , Borje Andersson  2 , Uday Popat  2 , Chitra Hosing  2 , Roy Jones  2 , Elizabeth J Shpall  2 , Issa Khouri  2 , Muzaffar Qazilbash  2 , Yago Nieto  2 , Nina Shah  2 , Sairah Ahmed  2 , Betul Oran  2 , Gheath Al Atrash  2 , Stefan Ciurea  2 , Partow Kebriaei  2 , Julianne Chen  2 , Gabriela Rondon  2 , Richard E Champlin  2
Affiliations
Clinical Trial

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

Amin M Alousi et al. Biol Blood Marrow Transplant. 2015 May.

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.

Keywords: Acute; Chronic; Graft-versus-host disease; Marrow; Stem cell transplantation.

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Figures

Figure 1
Figure 1
Comparison of Acute GVHD II–IV (a), Acute GVHD III/IV (b), Non-Relapse Mortality (c), Relapse (d) and Over-all Survival (e)in Recipients of GVHD Prophylaxis with Post-Cy (hashed line) and Tacrolimus/Methotrexate (solid line) following RIC allogeneic transplants from MRD and MUD’s
Figure 1
Figure 1
Comparison of Acute GVHD II–IV (a), Acute GVHD III/IV (b), Non-Relapse Mortality (c), Relapse (d) and Over-all Survival (e)in Recipients of GVHD Prophylaxis with Post-Cy (hashed line) and Tacrolimus/Methotrexate (solid line) following RIC allogeneic transplants from MRD and MUD’s
Figure 1
Figure 1
Comparison of Acute GVHD II–IV (a), Acute GVHD III/IV (b), Non-Relapse Mortality (c), Relapse (d) and Over-all Survival (e)in Recipients of GVHD Prophylaxis with Post-Cy (hashed line) and Tacrolimus/Methotrexate (solid line) following RIC allogeneic transplants from MRD and MUD’s
Figure 1
Figure 1
Comparison of Acute GVHD II–IV (a), Acute GVHD III/IV (b), Non-Relapse Mortality (c), Relapse (d) and Over-all Survival (e)in Recipients of GVHD Prophylaxis with Post-Cy (hashed line) and Tacrolimus/Methotrexate (solid line) following RIC allogeneic transplants from MRD and MUD’s
Figure 1
Figure 1
Comparison of Acute GVHD II–IV (a), Acute GVHD III/IV (b), Non-Relapse Mortality (c), Relapse (d) and Over-all Survival (e)in Recipients of GVHD Prophylaxis with Post-Cy (hashed line) and Tacrolimus/Methotrexate (solid line) following RIC allogeneic transplants from MRD and MUD’s
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