TY - JOUR
T1 - Phase II trial of graft-versus-host disease prophylaxis with post-transplantation cyclophosphamide after reduced-intensity busulfan/fludarabine conditioning for hematological malignancies
AU - Alousi, Amin M.
AU - Brammer, Jonathan E.
AU - Saliba, Rima M.
AU - Andersson, Borje
AU - Popat, Uday
AU - Hosing, Chitra
AU - Jones, Roy
AU - Shpall, Elizabeth J.
AU - Khouri, Issa
AU - Qazilbash, Muzaffar
AU - Nieto, Yago
AU - Shah, Nina
AU - Ahmed, Sairah
AU - Oran, Betul
AU - Al Atrash, Gheath
AU - Ciurea, Stefan
AU - Kebriaei, Partow
AU - Chen, Julianne
AU - Rondon, Gabriela
AU - Champlin, Richard E.
N1 - Publisher Copyright:
© 2015 American Society for Blood and Marrow Transplantation.
PY - 2015/5/1
Y1 - 2015/5/1
N2 - 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.
AB - 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.
KW - Acute
KW - Chronic
KW - Graft-versus-host disease
KW - Marrow
KW - Stem cell transplantation
UR - http://www.scopus.com/inward/record.url?scp=84928124919&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84928124919&partnerID=8YFLogxK
U2 - 10.1016/j.bbmt.2015.01.026
DO - 10.1016/j.bbmt.2015.01.026
M3 - Article
C2 - 25667989
AN - SCOPUS:84928124919
SN - 1083-8791
VL - 21
SP - 906
EP - 912
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
IS - 5
ER -