title: Reduced intensity haplo plus single cord transplant compared to double cord transplant: improved engraftment and graft-versus-host disease-free, relapse-free survival.
abstract: Umbilical cord blood stem cell transplants are commonly used in adults lacking HLA-identical donors. Delays in hematopoietic recovery contribute to mortality and morbidity. To hasten recovery, we used co-infusion of progenitor cells from a partially matched related donor and from an umbilical cord blood graft (haplo-cord transplant). Here we compared the outcomes of haplo-cord and double-cord transplants. A total of 97 adults underwent reduced intensity conditioning followed by haplo-cord transplant and 193 patients received reduced intensity conditioning followed by double umbilical cord blood transplantation. Patients in the haplo-cord group were more often from minority groups and had more advanced malignancy. Haplo-cord recipients received fludarabine-melphalan-anti-thymocyte globulin. Double umbilical cord blood recipients received fludarabine-cyclophosphamide and low-dose total body irradiation. In a multivariate analysis, haplo-cord had faster neutrophil (HR=1.42, P=0.007) and platelet (HR=2.54, P<0.0001) recovery, lower risk of grade II-IV acute graft-versus-host disease (HR=0.26, P<0.0001) and chronic graft-versus-host disease (HR=0.06, P<0.0001). Haplo-cord was associated with decreased risk of relapse (HR 0.48, P=0.001). Graft-versus-host disease-free, relapse-free survival was superior with haplo-cord (HR 0.63, P=0.002) but not overall survival (HR=0.97, P=0.85). Haplo-cord transplantation using fludarabine-melphalan-thymoglobulin conditioning hastens hematopoietic recovery with a lower risk of relapse relative to double umbilical cord blood transplantation using the commonly used fludarabine-cyclophosphamide-low-dose total body irradiation conditioning. Graft-versus-host disease-free and relapse-free survival is significantly improved. Haplo-cord is a readily available graft source that improves outcomes and access to transplant for those lacking HLA-matched donors. Trials registered at clinicaltrials.gov identifiers 00943800 and 01810588.
authors: Department of Hematology/Oncology and Meyer Cancer Center - Stem Cell Transplant Program, Weill Cornell Medical College, New York, NY, USA kov9001@med.cornell.edu.
authors: Koen
authors: K
authors: van Besien
authors: Center for International Bone Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, WI, USA.
authors: Parameswaran
authors: P
authors: Hari
authors: Center for International Bone Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, WI, USA.
authors: Mei-Jie
authors: MJ
authors: Zhang
authors: Section of Hematology/Oncology-Hematopoietic Cellular Therapy Program, University of Chicago, Il, USA.
authors: Hong-Tao
authors: HT
authors: Liu
authors: Section of Hematology/Oncology-Hematopoietic Cellular Therapy Program, University of Chicago, Il, USA.
authors: Wendy
authors: W
authors: Stock
authors: Section of Hematology/Oncology-Hematopoietic Cellular Therapy Program, University of Chicago, Il, USA.
authors: Lucy
authors: L
authors: Godley
authors: Section of Hematology/Oncology-Hematopoietic Cellular Therapy Program, University of Chicago, Il, USA.
authors: Olatoyosi
authors: O
authors: Odenike
authors: Section of Hematology/Oncology-Hematopoietic Cellular Therapy Program, University of Chicago, Il, USA.
authors: Richard
authors: R
authors: Larson
authors: Section of Hematology/Oncology-Hematopoietic Cellular Therapy Program, University of Chicago, Il, USA.
authors: Michael
authors: M
authors: Bishop
authors: Section of Hematology/Oncology-Hematopoietic Cellular Therapy Program, University of Chicago, Il, USA.
authors: Amittha
authors: A
authors: Wickrema
authors: Department of Hematology/Oncology and Meyer Cancer Center - Stem Cell Transplant Program, Weill Cornell Medical College, New York, NY, USA.
authors: Usama
authors: U
authors: Gergis
authors: Department of Hematology/Oncology and Meyer Cancer Center - Stem Cell Transplant Program, Weill Cornell Medical College, New York, NY, USA.
authors: Sebastian
authors: S
authors: Mayer
authors: Department of Hematology/Oncology and Meyer Cancer Center - Stem Cell Transplant Program, Weill Cornell Medical College, New York, NY, USA.
authors: Tsiporah
authors: T
authors: Shore
authors: Department of Hematology/Oncology and Meyer Cancer Center - Stem Cell Transplant Program, Weill Cornell Medical College, New York, NY, USA.
authors: Stephanie
authors: S
authors: Tsai
authors: Department of Hematology/Oncology and Meyer Cancer Center - Stem Cell Transplant Program, Weill Cornell Medical College, New York, NY, USA.
authors: Joanna
authors: J
authors: Rhodes
authors: Department of Pathology - Cellular Therapy Laboratory, Weill Cornell Medical College, New York, NY, USA.
authors: Melissa M
authors: MM
authors: Cushing
authors: Center for International Bone Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, WI, USA.
authors: Sandra
authors: S
authors: Korman
authors: Department of Hematology/Oncology and Meyer Cancer Center - Stem Cell Transplant Program, Weill Cornell Medical College, New York, NY, USA.
authors: Andrew
authors: A
authors: Artz
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015897:Comorbidity; D036101:Cord Blood Stem Cell Transplantation / Q000009:adverse effects; D018450:Disease Progression; D005260:Female; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology; D006239:Haplotypes; D019337:Hematologic Neoplasms / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000378:metabolism; D006650:Histocompatibility Testing; D006801:Humans; D053208:Kaplan-Meier Estimate; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009026:Mortality; D009504:Neutrophils; D012008:Recurrence; D019172:Transplantation Conditioning / Q000379:methods; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D061349:Unrelated Donors; D055815:Young Adult
chemical_list: D006680:HLA Antigens