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Low immunosuppressive burden after HLA-matched related or unrelated BMT using post-transplantation cyclophosphamide

Christopher G. Kanakry, Javier Bolaños-Meade, Yvette L. Kasamon, Marianna Zahurak, Nadira Durakovic, Terry Furlong, Marco Mielcarek, Marta Medeot, Ivana Gojo, B. Douglas Smith, Jennifer A. Kanakry, Ivan M. Borrello, Robert A. Brodsky, Douglas E. Gladstone, Carol Ann Huff, William H. Matsui, Lode J. Swinnen, Kenneth R. Cooke, Richard F. Ambinder, Ephraim J. Fuchs, Marcos J. de Lima, Borje S. Andersson, Ravi Varadhan, Paul V. O'Donnell, Richard J. Jones and Leo Luznik

Key points

  • 1) After PTCy, approximately 50% of MRD alloBMT patients and 30% of MUD alloBMT patients required no additional systemic immunosuppression.

  • 2) By 1-year post-transplant, the vast majority of patients had permanently discontinued all systemic immunosuppression.

Abstract

The intensive and prolonged immunosuppressive therapy required to prevent or treat graft-versus-host disease (GVHD) after allogeneic blood or marrow transplantation (alloBMT) puts patients at substantial risk for life-threatening infections, organ toxicity, and disease relapse. Post-transplantation cyclophosphamide (PTCy) can function as single-agent GVHD prophylaxis after myeloablative, HLA-matched-related (MRD) or HLA-matched-unrelated (MUD) T-cell-replete bone marrow allografting, obviating the need for additional prophylactic immunosuppression. However, patients who develop GVHD require supplemental treatment. We assessed the longitudinal requirement for immunosuppressive therapy in 339 patients treated with this transplantation platform: 247 receiving busulfan/cyclophosphamide (BuCy) conditioning (data collected retrospectively) and 92 receiving busulfan/fludarabine (BuFlu) conditioning (data collected prospectively). Approximately 50% of MRD patients and 30% of MUD patients never required immunosuppression beyond PTCy. In patients requiring further immunosuppression, typically 1-2 agents only were required, and the median durations of systemic pharmacologic immunosuppression for the BuCy MRD, BuFlu MRD, BuCy MUD, and BuFlu MUD groups all were 4.5-5 months. For these four groups, the 1-year probabilities of being alive and off all systemic immunosuppression were 61%, 53%, 53%, and 51% and the 3-year probabilities were 53%, 48%, 49%, and 56%, respectively. These data suggest that PTCy minimizes the global immunosuppressive burden experienced by patients undergoing HLA-matched alloBMT.

  • Submitted September 6, 2016.
  • Accepted December 1, 2016.