title: Single-agent GVHD prophylaxis with posttransplantation cyclophosphamide after myeloablative, HLA-matched BMT for AML, ALL, and MDS.
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.
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, The 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, The Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Hua-Ling
authors.initials: HL
authors.lastname: Tsai
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, The 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, The 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, The Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Ivana
authors.initials: I
authors.lastname: Gojo
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, The 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, The 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, The 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, The Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: William
authors.initials: W
authors.lastname: Matsui
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Ivan
authors.initials: I
authors.lastname: Borrello
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, The 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, The 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, The Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Powell
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Keith W
authors.initials: KW
authors.lastname: Pratz
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Amy E
authors.initials: AE
authors.lastname: DeZern
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Showel
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Michael A
authors.initials: MA
authors.lastname: McDevitt
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, The 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, The Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Levis
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, The 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, The Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Ephraim J
authors.initials: EJ
authors.lastname: Fuchs
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Gary L
authors.initials: GL
authors.lastname: Rosner
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, The 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, The Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Leo
authors.initials: L
authors.lastname: Luznik
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000379:methods*; D003520:Cyclophosphamide / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology / Q000517:prevention & control*; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007951:Leukemia, Myeloid / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000628:therapy*; D009364:Neoplasm Recurrence, Local; D018365:Neoplasm, Residual; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000628:therapy*; D012074:Remission Induction; D012189:Retrospective Studies; D013997:Time Factors; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D003520:Cyclophosphamide