title: Low immunosuppressive burden after HLA-matched related or unrelated BMT using posttransplantation cyclophosphamide.
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 HLA-matched 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 HLA-matched alloBMT.
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Kanakry
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Javier
authors.initials: J
authors.lastname: Bolaños-Meade
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Yvette L
authors.initials: YL
authors.lastname: Kasamon
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Marianna
authors.initials: M
authors.lastname: Zahurak
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Nadira
authors.initials: N
authors.lastname: Durakovic
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA; and.
authors.forename: Terry
authors.initials: T
authors.lastname: Furlong
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA; and.
authors.forename: Marco
authors.initials: M
authors.lastname: Mielcarek
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Marta
authors.initials: M
authors.lastname: Medeot
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Ivana
authors.initials: I
authors.lastname: Gojo
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: B Douglas
authors.initials: BD
authors.lastname: Smith
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Kanakry
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Ivan M
authors.initials: IM
authors.lastname: Borrello
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Brodsky
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Gladstone
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Carol Ann
authors.initials: CA
authors.lastname: Huff
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: William H
authors.initials: WH
authors.lastname: Matsui
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Lode J
authors.initials: LJ
authors.lastname: Swinnen
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Cooke
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Richard F
authors.initials: RF
authors.lastname: Ambinder
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Ephraim J
authors.initials: EJ
authors.lastname: Fuchs
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Marcos J
authors.initials: MJ
authors.lastname: de Lima
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Borje S
authors.initials: BS
authors.lastname: Andersson
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Ravi
authors.initials: R
authors.lastname: Varadhan
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA; and.
authors.forename: Paul V
authors.initials: PV
authors.lastname: O'Donnell
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Jones
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Leo
authors.initials: L
authors.lastname: Luznik
mesh_terms: D000328:Adult; D000368:Aged; D064591:Allografts; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D003520:Cyclophosphamide / Q000008:administration & dosage*; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged
chemical_list: D007166:Immunosuppressive Agents; D003520:Cyclophosphamide