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

Christopher G. Kanakry, Paul V. O'Donnell, Terry Furlong, Marcos J. De Lima, Wei Wei, Marta Medeot, Marco Mielcarek, Richard E. Champlin, Richard J. Jones, Peter F. Thall, Borje S. Andersson, Leo Luznik

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3497-3505
Number of pages9
JournalJournal of Clinical Oncology
Volume32
Issue number31
DOIs
StatePublished - Nov 1 2014

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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