TY - JOUR
T1 - Multi-institutional study of post-transplantation cyclophosphamide as single-agent graft-versus-host disease prophylaxis after allogeneic bone marrow transplantation using myeloablative busulfan and fludarabine conditioning
AU - Kanakry, Christopher G.
AU - O'Donnell, Paul V.
AU - Furlong, Terry
AU - De Lima, Marcos J.
AU - Wei, Wei
AU - Medeot, Marta
AU - Mielcarek, Marco
AU - Champlin, Richard E.
AU - Jones, Richard J.
AU - Thall, Peter F.
AU - Andersson, Borje S.
AU - Luznik, Leo
N1 - Publisher Copyright:
© 2014 by American Society of Clinical Oncology.
PY - 2014/11/1
Y1 - 2014/11/1
N2 - Purpose: The clinical safety and efficacy of intravenous busulfan and fludarabine (IV Bu/Flu) myeloablative conditioning as well as graft-versus-host disease (GVHD) prophylaxis with high-dose, posttransplantation cyclophosphamide (PTCy) have been demonstrated independently in several singleinstitutional studies. We hypothesized that combining these two promising approaches in a multiinstitutional study of human leukocyte antigen (HLA)-matched bone marrow transplantation would provide low rates of severe acute and chronic GVHD, low toxicity, and effective disease control.Patients and Methods: Ninety-two adult patients (median age, 49 years; range, 21 to 65 years) with high-risk hematologic malignancies were enrolled at three centers (clinical trial No. NCT00809276). Forty-five patients received related allografts, and 47 received unrelated allografts. GVHD prophylaxis was solely with PTCy at 50 mg/kg/day on post-transplantation days +3 and +4.Results: The cumulative incidences of grades 2 to 4 acute, grades 3 to 4 acute, and chronic GVHD were 51%, 15%, and 14%, respectively. Nonrelapse mortality (NRM) at 100 days and 1 year were 9% and 16%, respectively. With a median follow-up period of 2.2 years, the 2-year disease-free survival (DFS) and overall survival (OS) rates were 62% and 67%, respectively. Donor relatedness did not affect NRM, DFS, or OS. Patients in complete remission (CR) without evidence of minimal residual disease (MRD) had markedly better DFS (80%) and OS (80%) than patients in CR with MRD or with active disease at the time of transplantation (DFS, P =.0005; OS, P =.019).Conclusion: This multi-institutional study demonstrates that PTCy can be safely and effectively combined with IV Bu/Flu myeloablative conditioning and confirms PTCy's efficacy as single-agent, short-course GVHD prophylaxis for both acute and chronic GVHD after bone marrow transplantation from HLA-matched donors.
AB - Purpose: The clinical safety and efficacy of intravenous busulfan and fludarabine (IV Bu/Flu) myeloablative conditioning as well as graft-versus-host disease (GVHD) prophylaxis with high-dose, posttransplantation cyclophosphamide (PTCy) have been demonstrated independently in several singleinstitutional studies. We hypothesized that combining these two promising approaches in a multiinstitutional study of human leukocyte antigen (HLA)-matched bone marrow transplantation would provide low rates of severe acute and chronic GVHD, low toxicity, and effective disease control.Patients and Methods: Ninety-two adult patients (median age, 49 years; range, 21 to 65 years) with high-risk hematologic malignancies were enrolled at three centers (clinical trial No. NCT00809276). Forty-five patients received related allografts, and 47 received unrelated allografts. GVHD prophylaxis was solely with PTCy at 50 mg/kg/day on post-transplantation days +3 and +4.Results: The cumulative incidences of grades 2 to 4 acute, grades 3 to 4 acute, and chronic GVHD were 51%, 15%, and 14%, respectively. Nonrelapse mortality (NRM) at 100 days and 1 year were 9% and 16%, respectively. With a median follow-up period of 2.2 years, the 2-year disease-free survival (DFS) and overall survival (OS) rates were 62% and 67%, respectively. Donor relatedness did not affect NRM, DFS, or OS. Patients in complete remission (CR) without evidence of minimal residual disease (MRD) had markedly better DFS (80%) and OS (80%) than patients in CR with MRD or with active disease at the time of transplantation (DFS, P =.0005; OS, P =.019).Conclusion: This multi-institutional study demonstrates that PTCy can be safely and effectively combined with IV Bu/Flu myeloablative conditioning and confirms PTCy's efficacy as single-agent, short-course GVHD prophylaxis for both acute and chronic GVHD after bone marrow transplantation from HLA-matched donors.
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U2 - 10.1200/JCO.2013.54.0625
DO - 10.1200/JCO.2013.54.0625
M3 - Article
C2 - 25267759
AN - SCOPUS:84911460779
SN - 0732-183X
VL - 32
SP - 3497
EP - 3505
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 31
ER -