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Risk Factors for Graft-versus-Host Disease in Haploidentical Hematopoietic Cell Transplantation Using Post-Transplant Cyclophosphamide.
Biol Blood Marrow Transplant. 2020 Aug; 26(8):1459-1468.BB

Abstract

Post-transplant cyclophosphamide (PTCy) has significantly increased the successful use of haploidentical donors with a relatively low incidence of graft-versus-host disease (GVHD). Given its increasing use, we sought to determine risk factors for GVHD after haploidentical hematopoietic cell transplantation (haplo-HCT) using PTCy. Data from the Center for International Blood and Marrow Transplant Research on adult patients with acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, or chronic myeloid leukemia who underwent PTCy-based haplo-HCT (2013 to 2016) were analyzed and categorized into 4 groups based on myeloablative (MA) or reduced-intensity conditioning (RIC) and bone marrow (BM) or peripheral blood (PB) graft source. In total, 646 patients were identified (MA-BM = 79, MA-PB = 183, RIC-BM = 192, RIC-PB = 192). The incidence of grade 2 to 4 acute GVHD at 6 months was highest in MA-PB (44%), followed by RIC-PB (36%), MA-BM (36%), and RIC-BM (30%) (P = .002). The incidence of chronic GVHD at 1 year was 40%, 34%, 24%, and 20%, respectively (P < .001). In multivariable analysis, there was no impact of stem cell source or conditioning regimen on grade 2 to 4 acute GVHD; however, older donor age (30 to 49 versus <29 years) was significantly associated with higher rates of grade 2 to 4 acute GVHD (hazard ratio [HR], 1.53; 95% confidence interval [CI], 1.11 to 2.12; P = .01). In contrast, PB compared to BM as a stem cell source was a significant risk factor for the development of chronic GVHD (HR, 1.70; 95% CI, 1.11 to 2.62; P = .01) in the RIC setting. There were no differences in relapse or overall survival between groups. Donor age and graft source are risk factors for acute and chronic GVHD, respectively, after PTCy-based haplo-HCT. Our results indicate that in RIC haplo-HCT, the risk of chronic GVHD is higher with PB stem cells, without any difference in relapse or overall survival.

Authors+Show Affiliations

University of Pittsburgh/UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania.Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, Minnesota.Department of Medicine, Medical College of Wisconsin, CIBMTR® (Center for International Blood and Marrow Transplant Research), Milwaukee, Wisconsin; Division of Biostatistics, Institute for Health and Equity, Medical College of Wisconsin, Milwaukee, Wisconsin.Department of Medicine, Medical College of Wisconsin, CIBMTR® (Center for International Blood and Marrow Transplant Research), Milwaukee, Wisconsin.Blood and Marrow Transplant Program, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota.H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.Vanderbilt University Medical Center, Nashville, Tennessee.Immune Deficiency Cellular Therapy Program, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland.Blood & Marrow Transplant Program, Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio.Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, Minnesota.(0)Division of Hematology, Oncology and Blood & Marrow Transplantation, Children's Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, California.Division of Hematology-Oncology, Indiana University School of Medicine, Indianapolis, Indiana.(2)New York University Langone Medical Center, New York, New York.(3)Department of Oncology, King Faisal Specialist Hospital Center & Research, Riyadh, Saudi Arabia.(4)Department of Pathology and Laboratory Medicine, Baylor University Medical Center, Dallas, Texas.(5)Blood and Marrow Transplant Program and Host Defense Program, Divisions of Hematology/Oncology/Bone Marrow Transplant and Infectious Diseases, Nationwide Children's Hospital, Columbus, Ohio.(6)Blood and Marrow Transplant Program at Northside Hospital, Atlanta, Georgia.(7)Department of Hematology and Oncology, University of Miami, Miami, Florida.(8)The Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, Nebraska.Vanderbilt University Medical Center, Nashville, Tennessee.Department of Hematology, CHU Grenoble Alpes, Grenoble, France.(0)Division of Pediatric Hematology, Oncology and Stem Cell Transplantation, Department of Pediatrics, New York Medical College, Valhalla, New York.(1)UF Health Shands Children's Hospital, Gainesville, Florida.Division of Hematology/Oncology, Department of Medicine, University of Massachusetts Medical Center, Worcester, Massachusetts.Department of Medicine, Medical College of Wisconsin, CIBMTR® (Center for International Blood and Marrow Transplant Research), Milwaukee, Wisconsin.(3)James Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, Columbus, Ohio.(4)The University of Texas MD Anderson Cancer Center, Houston, Texas.(5)Tom Baker Cancer Center, Calgary, Alberta, Canada.(6)Department of Hematology/Oncology, Hospital Infantil Universitario Nino Jesus, Madrid, Spain.(7)Division of Hematology/Oncology, University of Florida College of Medicine, Gainesville, Florida.(8)Division of Cancer Epidemiology & Genetics, NIH-NCI Clinical Genetics Branch, Rockville, Maryland.Hematology Research Centre, Division of Experimental Medicine, Department of Medicine, Imperial College London, London, United Kingdom.(0)Division of Hematological Malignancy and Cellular Therapeutics, University of Kansas Health System, Kansas City, Kansas.(1)Department of Medical Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania.(2)Cleveland Clinic Foundation, Cleveland, Ohio.Division of Hematology/Oncology/Bone Marrow Transplantation, Department of Medicine, University of Wisconsin, Madison, Wisconsin.(4)University of Kentucky Chandler Medical Center, Louisville, Kentucky.(5)Markey Cancer Center, University of Kentucky, Lexington, Kentucky.(6)Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India.(7)Utah Blood and Marrow Transplant Program at Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah.(8)Dana-Farber Cancer Institute/Boston Children's Hospital, Boston, Massachusetts.(7)Department of Hematology and Oncology, University of Miami, Miami, Florida.Division of Hematology and Oncology, Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas.(0)Division of Hematology-Oncology, Blood and Marrow Transplantation Program, Mayo Clinic, Jacksonville, Florida.(1)Division of Bone Marrow Transplant and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; (2)Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio.(3)Divison of Clinical Hematology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.(0)Division of Hematology-Oncology, Blood and Marrow Transplantation Program, Mayo Clinic, Jacksonville, Florida.Department of Blood & Marrow Transplant and Cellular Immunotherapy (BMT CI), Moffitt Cancer Center, Tampa, Florida.(5)Blood & Marrow Transplant Program, Kids Cancer Centre, Sydney Children's Hospital, Sydney, Australia.(6)Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden; (7)Centre for Clinical Research Sormland, Uppsala University, Uppsala, Sweden.(8)Blood and Marrow Transplant Program, University of Utah, Salt Lake City, Utah.Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.(0)Blood and Cancer Centre, Starship Children's Hospital, Auckland, New Zealand.(1)Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia.(2)Dana Farber Cancer Institute, Boston, Massachusetts.(3)Department of Hematology, University Hospitals Leuven and KU Leuven, Leuven, Belgium.(4)Department of Hematology and Oncology, Dokkyo Medical University, Tochigi, Japan.Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, Tennessee.(6)The Blood and Marrow Transplant Group of Georgia, Northside Hospital, Atlanta, Georgia.(7)Rutgers Cancer Institute of New Jersey, Rutgers University, Brunswick, New Jersey.(8)Hokkaido University Hospital, Sapporo, Japan.Department of Hematology, Hospital Clinic, University of Barcelona, IDIBAPS, and Institute of Research Josep Carreras, Barcelona, Spain.(0)Maastricht University Medical Center, Maastricht, the Netherlands.(1)Division of Hematology and Oncology, Washington University School of Medicine, St. Louis, Missouri.(2)Department of Medical Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania.(3)Division of Hematology, The Ohio State University, Columbus, Ohio.(4)Bone Marrow Transplant Program, Penn State Cancer Institute, Hershey, Pennsylvania.(5)Blood & Marrow Transplantation Program, Division of Hematology/Oncology, Department of Medicine, Greenebaum Comprehensive Cancer Center, University of Maryland, Baltimore, Maryland.Department of Medicine, Medical College of Wisconsin, CIBMTR® (Center for International Blood and Marrow Transplant Research), Milwaukee, Wisconsin.Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, Minnesota.Blood & Marrow Transplant Program, Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio. Electronic address: hamiltb2@ccf.org.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32434056

Citation

Im, Annie, et al. "Risk Factors for Graft-versus-Host Disease in Haploidentical Hematopoietic Cell Transplantation Using Post-Transplant Cyclophosphamide." Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation, vol. 26, no. 8, 2020, pp. 1459-1468.
Im A, Rashidi A, Wang T, et al. Risk Factors for Graft-versus-Host Disease in Haploidentical Hematopoietic Cell Transplantation Using Post-Transplant Cyclophosphamide. Biol Blood Marrow Transplant. 2020;26(8):1459-1468.
Im, A., Rashidi, A., Wang, T., Hemmer, M., MacMillan, M. L., Pidala, J., Jagasia, M., Pavletic, S., Majhail, N. S., Weisdorf, D., Abdel-Azim, H., Agrawal, V., Al-Homsi, A. S., Aljurf, M., Askar, M., Auletta, J. J., Bashey, A., Beitinjaneh, A., Bhatt, V. R., ... Hamilton, B. K. (2020). Risk Factors for Graft-versus-Host Disease in Haploidentical Hematopoietic Cell Transplantation Using Post-Transplant Cyclophosphamide. Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation, 26(8), 1459-1468. https://doi.org/10.1016/j.bbmt.2020.05.001
Im A, et al. Risk Factors for Graft-versus-Host Disease in Haploidentical Hematopoietic Cell Transplantation Using Post-Transplant Cyclophosphamide. Biol Blood Marrow Transplant. 2020;26(8):1459-1468. PubMed PMID: 32434056.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Risk Factors for Graft-versus-Host Disease in Haploidentical Hematopoietic Cell Transplantation Using Post-Transplant Cyclophosphamide. AU - Im,Annie, AU - Rashidi,Armin, AU - Wang,Tao, AU - Hemmer,Michael, AU - MacMillan,Margaret L, AU - Pidala,Joseph, AU - Jagasia,Madan, AU - Pavletic,Steven, AU - Majhail,Navneet S, AU - Weisdorf,Daniel, AU - Abdel-Azim,Hisham, AU - Agrawal,Vaibhav, AU - Al-Homsi,A Samer, AU - Aljurf,Mahmoud, AU - Askar,Medhat, AU - Auletta,Jeffery J, AU - Bashey,Asad, AU - Beitinjaneh,Amer, AU - Bhatt,Vijaya Raj, AU - Byrne,Michael, AU - Cahn,Jean-Yves, AU - Cairo,Mitchell, AU - Castillo,Paul, AU - Cerny,Jan, AU - Chhabra,Saurabh, AU - Choe,Hannah, AU - Ciurea,Stefan, AU - Daly,Andrew, AU - Perez,Miguel Angel Diaz, AU - Farhadfar,Nosha, AU - Gadalla,Shahinaz M, AU - Gale,Robert, AU - Ganguly,Siddhartha, AU - Gergis,Usama, AU - Hanna,Rabi, AU - Hematti,Peiman, AU - Herzig,Roger, AU - Hildebrandt,Gerhard C, AU - Lad,Deepesh P, AU - Lee,Catherine, AU - Lehmann,Leslie, AU - Lekakis,Lazaros, AU - Kamble,Rammurti T, AU - Kharfan-Dabaja,Mohamed A, AU - Khandelwal,Pooja, AU - Martino,Rodrigo, AU - Murthy,Hemant S, AU - Nishihori,Taiga, AU - O'Brien,Tracey A, AU - Olsson,Richard F, AU - Patel,Sagar S, AU - Perales,Miguel-Angel, AU - Prestidge,Tim, AU - Qayed,Muna, AU - Romee,Rizwan, AU - Schoemans,Hélène, AU - Seo,Sachiko, AU - Sharma,Akshay, AU - Solh,Melhem, AU - Strair,Roger, AU - Teshima,Takanori, AU - Urbano-Ispizua,Alvaro, AU - Van der Poel,Marjolein, AU - Vij,Ravi, AU - Wagner,John L, AU - William,Basem, AU - Wirk,Baldeep, AU - Yared,Jean A, AU - Spellman,Steve R, AU - Arora,Mukta, AU - Hamilton,Betty K, Y1 - 2020/05/17/ PY - 2020/01/08/received PY - 2020/03/31/revised PY - 2020/05/04/accepted PY - 2021/08/01/pmc-release PY - 2020/5/21/pubmed PY - 2020/5/21/medline PY - 2020/5/21/entrez SP - 1459 EP - 1468 JF - Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation JO - Biol. Blood Marrow Transplant. VL - 26 IS - 8 N2 - Post-transplant cyclophosphamide (PTCy) has significantly increased the successful use of haploidentical donors with a relatively low incidence of graft-versus-host disease (GVHD). Given its increasing use, we sought to determine risk factors for GVHD after haploidentical hematopoietic cell transplantation (haplo-HCT) using PTCy. Data from the Center for International Blood and Marrow Transplant Research on adult patients with acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, or chronic myeloid leukemia who underwent PTCy-based haplo-HCT (2013 to 2016) were analyzed and categorized into 4 groups based on myeloablative (MA) or reduced-intensity conditioning (RIC) and bone marrow (BM) or peripheral blood (PB) graft source. In total, 646 patients were identified (MA-BM = 79, MA-PB = 183, RIC-BM = 192, RIC-PB = 192). The incidence of grade 2 to 4 acute GVHD at 6 months was highest in MA-PB (44%), followed by RIC-PB (36%), MA-BM (36%), and RIC-BM (30%) (P = .002). The incidence of chronic GVHD at 1 year was 40%, 34%, 24%, and 20%, respectively (P < .001). In multivariable analysis, there was no impact of stem cell source or conditioning regimen on grade 2 to 4 acute GVHD; however, older donor age (30 to 49 versus <29 years) was significantly associated with higher rates of grade 2 to 4 acute GVHD (hazard ratio [HR], 1.53; 95% confidence interval [CI], 1.11 to 2.12; P = .01). In contrast, PB compared to BM as a stem cell source was a significant risk factor for the development of chronic GVHD (HR, 1.70; 95% CI, 1.11 to 2.62; P = .01) in the RIC setting. There were no differences in relapse or overall survival between groups. Donor age and graft source are risk factors for acute and chronic GVHD, respectively, after PTCy-based haplo-HCT. Our results indicate that in RIC haplo-HCT, the risk of chronic GVHD is higher with PB stem cells, without any difference in relapse or overall survival. SN - 1523-6536 UR - https://www.unboundmedicine.com/medline/citation/32434056/Risk_Factors_for_Graft-versus-Host_Disease_in_Haploidentical_Hematopoietic_Cell_Transplantation_Using_Post-Transplant_Cyclophosphamide L2 - https://linkinghub.elsevier.com/retrieve/pii/S1083-8791(20)30286-X DB - PRIME DP - Unbound Medicine ER -
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