Low immunosuppressive burden after HLA-matched related or unrelated BMT using posttransplantation 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 & 6 others Marcos J. De Lima, Borje S. Andersson, Ravi Varadhan, Paul V. O'Donnell, Richard J. Jones, Leo Luznik

Research output: Research - peer-reviewArticle

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. Posttransplantation cyclophosphamide (PTCy) can function as single-agent GVHD prophylaxis after myeloablative, HLA-matched related (MRD), or HLAmatched unrelated (MUD) donor 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 only 1 to 2 agents 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 to 5 months. For these 4 groups, 1-year probabilities of being alive and off all systemic immunosuppression were 61%, 53%, 53%, and 51% and 3-year probabilities were 53%, 48%, 49%, and 56%, respectively. These data suggest that PTCy minimizes the global immunosuppressive burden experienced by patients undergoing HLAmatched alloBMT.

LanguageEnglish (US)
Pages1389-1393
Number of pages5
JournalBlood
Volume129
Issue number10
DOIs
StatePublished - Mar 9 2017

Fingerprint

Immunosuppressive Agents
Cyclophosphamide
Busulfan
Immunosuppression
Grafts
fludarabine
Graft vs Host Disease
Transplantation
Bone Marrow
Therapeutics
Blood
T-cells
Toxicity
Bone
Unrelated Donors
Homologous Transplantation
T-Lymphocytes
Recurrence
Infection

ASJC Scopus subject areas

  • Immunology
  • Biochemistry
  • Hematology
  • Cell Biology

Cite this

Low immunosuppressive burden after HLA-matched related or unrelated BMT using posttransplantation cyclophosphamide. / Kanakry, Christopher G.; Bolaños-Meade, Javier; Kasamon, Yvette L.; Zahurak, Marianna; Durakovic, Nadira; Furlong, Terry; Mielcarek, Marco; Medeot, Marta; Gojo, Ivana; Smith, B. Douglas; Kanakry, Jennifer A.; Borrello, Ivan M.; Brodsky, Robert A.; Gladstone, Douglas E.; Huff, Carol Ann; Matsui, William H.; Swinnen, Lode J.; Cooke, Kenneth R.; Ambinder, Richard F.; Fuchs, Ephraim J.; De Lima, Marcos J.; Andersson, Borje S.; Varadhan, Ravi; O'Donnell, Paul V.; Jones, Richard J.; Luznik, Leo.

In: Blood, Vol. 129, No. 10, 09.03.2017, p. 1389-1393.

Research output: Research - peer-reviewArticle

Kanakry CG, Bolaños-Meade J, Kasamon YL, Zahurak M, Durakovic N, Furlong T et al. Low immunosuppressive burden after HLA-matched related or unrelated BMT using posttransplantation cyclophosphamide. Blood. 2017 Mar 9;129(10):1389-1393. Available from, DOI: 10.1182/blood-2016-09-737825
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AU - Zahurak,Marianna

AU - Durakovic,Nadira

AU - Furlong,Terry

AU - Mielcarek,Marco

AU - Medeot,Marta

AU - Gojo,Ivana

AU - Smith,B. Douglas

AU - Kanakry,Jennifer A.

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AU - Huff,Carol Ann

AU - Matsui,William H.

AU - Swinnen,Lode J.

AU - Cooke,Kenneth R.

AU - Ambinder,Richard F.

AU - Fuchs,Ephraim J.

AU - De Lima,Marcos J.

AU - Andersson,Borje S.

AU - Varadhan,Ravi

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AU - Jones,Richard J.

AU - Luznik,Leo

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