title: Comparable composite endpoints after HLA-matched and HLA-haploidentical transplantation with post-transplantation cyclophosphamide.
abstract: Composite endpoints that not only encompass mortality and relapse, but other critical post-transplant events such as graft-versus-host disease, are being increasingly utilized to quantify survival without significant morbidity after allogeneic blood or marrow transplantation. High-dose, post-transplantation cyclophosphamide reduces severe graft-versus-host disease with allogeneic marrow transplantation, making composite endpoints after this management particularly interesting. We retrospectively analyzed 684 adults with hematologic malignancies who received T-cell-replete bone marrow grafts and cyclophosphamide after myeloablative HLA-matched related (n=192) or unrelated (n=120), or non-myeloablative HLA-haploidentical (n=372) donor transplantation. The median follow up was 4 (range, 0.02-11.4) years. Graft-versus-host disease-free, relapse-free survival was defined as the time after transplantation without grade III-IV acute graft-versus-host disease, chronic graft-versus-host disease requiring systemic treatment, relapse, or death. Chronic graft-versus-host disease-free, relapse-free survival was defined as the time after transplantation without moderate or severe chronic graft-versus-host disease, relapse, or death. One-year graft-versus-host disease-free, relapse-free survival and chronic graft-versus-host disease-free, relapse-free survival estimates were, respectively, 47% (95% CI: 41-55%) and 53% (95% CI: 46-61%) after myeloablative HLA-matched related, 42% (95% CI: 34-52%) and 52% (95% CI: 44-62%) after myeloablative HLA-matched unrelated, and 45% (95% CI: 40-50%) and 50% (95% CI: 45-55%) after non-myeloablative HLA-haploidentical donor transplantation. In multivariable models, there were no differences in graft-versus-host disease-free, or chronic graft-versus-host disease-free, relapse-free survival after either myeloablative HLA-matched unrelated or non-myeloablative HLA-haploidentical, compared with myeloablative HLA-matched related donor transplantation. Although limited by inclusion of dissimilar cohorts, we found that post-transplantation cyclophosphamide-based platforms yield comparable composite endpoints across conditioning intensity, donor type, and HLA match.
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Shannon R
authors.initials: SR
authors.lastname: McCurdy
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
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, USA.
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, USA.
authors.forename: Javier
authors.initials: J
authors.lastname: Bolaños-Meade
authors.affiliation: Biostatistics & Bioinformatics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Hua-Ling
authors.initials: HL
authors.lastname: Tsai
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Showel
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
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, USA.
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Symons
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Ivana
authors.initials: I
authors.lastname: Gojo
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: B Douglas
authors.initials: BD
authors.lastname: Smith
authors.affiliation: Immunogenetics Laboratory, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Maria P
authors.initials: MP
authors.lastname: Bettinotti
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
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, USA.
authors.forename: Amy E
authors.initials: AE
authors.lastname: Dezern
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
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, USA.
authors.forename: Ivan
authors.initials: I
authors.lastname: Borrello
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Keith W
authors.initials: KW
authors.lastname: Pratz
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
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, USA.
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, USA.
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, USA.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Levis
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
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, USA.
authors.forename: Ephraim J
authors.initials: EJ
authors.lastname: Fuchs
authors.affiliation: Immunogenetics Laboratory, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Gary L
authors.initials: GL
authors.lastname: Rosner
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
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, USA luznile@jhmi.edu.
authors.forename: Leo
authors.initials: L
authors.lastname: Luznik
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016026:Bone Marrow Transplantation / Q000009:adverse effects; D018890:Chemoprevention; D002648:Child; D003520:Cyclophosphamide / Q000627:therapeutic use*; D003586:Cytomegalovirus Infections / Q000209:etiology; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D006680:HLA Antigens / Q000235:genetics* / Q000276:immunology*; D006239:Haplotypes; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011182:Postoperative Care; D012008:Recurrence; D014019:Tissue Donors; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D006680:HLA Antigens; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide