Single-agent GVHD prophylaxis with posttransplantation cyclophosphamide after myeloablative, HLA-matched BMT for AML, ALL, and MDS

Blood. 2014 Dec 11;124(25):3817-27. doi: 10.1182/blood-2014-07-587477. Epub 2014 Oct 14.

Abstract

High-dose, posttransplantation cyclophosphamide (PTCy) reduces severe graft-versus-host disease (GVHD) after allogeneic blood or marrow transplantation (alloBMT), but the impact of PTCy on long-term, disease-specific outcomes is unclear. We conducted a retrospective study of 209 consecutive adult patients transplanted for acute myeloid leukemia (AML, n = 138), myelodysplastic syndrome (n = 28), or acute lymphoblastic leukemia (ALL, n = 43) using PTCy as sole GVHD prophylaxis after myeloablative conditioning and HLA-matched-related or -unrelated T-cell-replete allografting. At alloBMT, 30% of patients were not in morphologic complete remission. The cumulative incidences of grades II to IV and III to IV acute GVHD at 100 days and chronic GVHD at 2 years were 45%, 11%, and 13%, respectively. Forty-three percent of patients did not require immunosuppression for any reason beyond PTCy. At 3 years, relapse cumulative incidence was 36%, disease-free survival was 46%, survival free of disease and chronic GVHD was 39%, and overall survival was 58%. Lack of remission at alloBMT, adverse cytogenetics, and low allograft nucleated cell dose were associated with inferior survival for AML patients. Minimal residual disease but not t(9;22) was associated with inferior outcomes for ALL patients. The ability to limit posttransplantation immunosuppression makes PTCy a promising transplantation platform for the integration of postgrafting strategies to prevent relapse.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adolescent
  • Adult
  • Aged
  • Bone Marrow Transplantation / adverse effects
  • Bone Marrow Transplantation / methods*
  • Cyclophosphamide / therapeutic use*
  • Disease-Free Survival
  • Female
  • Graft vs Host Disease / etiology
  • Graft vs Host Disease / prevention & control*
  • Histocompatibility Testing
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Leukemia, Myeloid / therapy*
  • Male
  • Middle Aged
  • Myelodysplastic Syndromes / therapy*
  • Neoplasm Recurrence, Local
  • Neoplasm, Residual
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy*
  • Remission Induction
  • Retrospective Studies
  • Time Factors
  • Transplantation, Homologous
  • Treatment Outcome
  • Young Adult

Substances

  • Immunosuppressive Agents
  • Cyclophosphamide