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Reduced intensity haplo plus single cord transplant compared to double cord transplant: improved engraftment and graft-versus-host disease-free, relapse-free survival.
Haematologica. 2016 05; 101(5):634-43.H

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+Show Affiliations

Department of Hematology/Oncology and Meyer Cancer Center - Stem Cell Transplant Program, Weill Cornell Medical College, New York, NY, USA kov9001@med.cornell.edu.Center for International Bone Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, WI, USA.Center for International Bone Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, WI, USA.Section of Hematology/Oncology-Hematopoietic Cellular Therapy Program, University of Chicago, Il, USA.Section of Hematology/Oncology-Hematopoietic Cellular Therapy Program, University of Chicago, Il, USA.Section of Hematology/Oncology-Hematopoietic Cellular Therapy Program, University of Chicago, Il, USA.Section of Hematology/Oncology-Hematopoietic Cellular Therapy Program, University of Chicago, Il, USA.Section of Hematology/Oncology-Hematopoietic Cellular Therapy Program, University of Chicago, Il, USA.Section of Hematology/Oncology-Hematopoietic Cellular Therapy Program, University of Chicago, Il, USA.Section of Hematology/Oncology-Hematopoietic Cellular Therapy Program, University of Chicago, Il, USA.Department of Hematology/Oncology and Meyer Cancer Center - Stem Cell Transplant Program, Weill Cornell Medical College, New York, NY, USA.Department of Hematology/Oncology and Meyer Cancer Center - Stem Cell Transplant Program, Weill Cornell Medical College, New York, NY, USA.Department of Hematology/Oncology and Meyer Cancer Center - Stem Cell Transplant Program, Weill Cornell Medical College, New York, NY, USA.Department of Hematology/Oncology and Meyer Cancer Center - Stem Cell Transplant Program, Weill Cornell Medical College, New York, NY, USA.Department of Hematology/Oncology and Meyer Cancer Center - Stem Cell Transplant Program, Weill Cornell Medical College, New York, NY, USA.Department of Pathology - Cellular Therapy Laboratory, Weill Cornell Medical College, New York, NY, USA.Center for International Bone Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, WI, USA.Department of Hematology/Oncology and Meyer Cancer Center - Stem Cell Transplant Program, Weill Cornell Medical College, New York, NY, USA.

Pub Type(s)

Clinical Trial
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26869630

Citation

van Besien, Koen, et al. "Reduced Intensity Haplo Plus Single Cord Transplant Compared to Double Cord Transplant: Improved Engraftment and Graft-versus-host Disease-free, Relapse-free Survival." Haematologica, vol. 101, no. 5, 2016, pp. 634-43.
van Besien K, Hari P, Zhang MJ, et al. Reduced intensity haplo plus single cord transplant compared to double cord transplant: improved engraftment and graft-versus-host disease-free, relapse-free survival. Haematologica. 2016;101(5):634-43.
van Besien, K., Hari, P., Zhang, M. J., Liu, H. T., Stock, W., Godley, L., Odenike, O., Larson, R., Bishop, M., Wickrema, A., Gergis, U., Mayer, S., Shore, T., Tsai, S., Rhodes, J., Cushing, M. M., Korman, S., & Artz, A. (2016). Reduced intensity haplo plus single cord transplant compared to double cord transplant: improved engraftment and graft-versus-host disease-free, relapse-free survival. Haematologica, 101(5), 634-43. https://doi.org/10.3324/haematol.2015.138594
van Besien K, et al. Reduced Intensity Haplo Plus Single Cord Transplant Compared to Double Cord Transplant: Improved Engraftment and Graft-versus-host Disease-free, Relapse-free Survival. Haematologica. 2016;101(5):634-43. PubMed PMID: 26869630.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Reduced intensity haplo plus single cord transplant compared to double cord transplant: improved engraftment and graft-versus-host disease-free, relapse-free survival. AU - van Besien,Koen, AU - Hari,Parameswaran, AU - Zhang,Mei-Jie, AU - Liu,Hong-Tao, AU - Stock,Wendy, AU - Godley,Lucy, AU - Odenike,Olatoyosi, AU - Larson,Richard, AU - Bishop,Michael, AU - Wickrema,Amittha, AU - Gergis,Usama, AU - Mayer,Sebastian, AU - Shore,Tsiporah, AU - Tsai,Stephanie, AU - Rhodes,Joanna, AU - Cushing,Melissa M, AU - Korman,Sandra, AU - Artz,Andrew, Y1 - 2016/02/11/ PY - 2015/10/27/received PY - 2016/02/05/accepted PY - 2016/2/13/entrez PY - 2016/2/13/pubmed PY - 2017/7/8/medline SP - 634 EP - 43 JF - Haematologica JO - Haematologica VL - 101 IS - 5 N2 - 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. SN - 1592-8721 UR - https://www.unboundmedicine.com/medline/citation/26869630/Reduced_intensity_haplo_plus_single_cord_transplant_compared_to_double_cord_transplant:_improved_engraftment_and_graft_versus_host_disease_free_relapse_free_survival_ L2 - https://doi.org/10.3324/haematol.2015.138594 DB - PRIME DP - Unbound Medicine ER -