Rohtesh S Mehta1, Shernan G Holtan2, Tao Wang3,4, Michael T Hemmer3, Stephen R Spellman5, Mukta Arora6, Daniel R Couriel7, Amin M Alousi1, Joseph Pidala8, Hisham Abdel-Azim9, Vaibhav Agrawal10, Ibrahim Ahmed11, A Samer Al-Homsi12, Mahmoud Aljurf13, Joseph H Antin14, Medhat Askar15, Jeffery J Auletta16, Vijaya Raj Bhatt17, Lynette Chee18, Saurabh Chhabra19, Andrew Daly20, Zachariah DeFilipp21, James Gajewski22, Robert Peter Gale23, Usama Gergis24, Peiman Hematti25, Gerhard C Hildebrandt26, William J Hogan27, Yoshihiro Inamoto28, Rodrigo Martino29, Navneet S Majhail30, David I Marks31, Taiga Nishihori8, Richard F Olsson32,33, Attaphol Pawarode34, Miguel Angel Diaz35, Tim Prestidge36, Hemalatha G Rangarajan16, Olle Ringden32, Ayman Saad37, Bipin N Savani38, Hélène Schoemans39, Sachiko Seo40, Kirk R Schultz41, Melhem Solh42, Thomas Spitzer20, Jan Storek43, Takanori Teshima44, Leo F Verdonck45, Baldeep Wirk46, Jean A Yared47, Jean-Yves Cahn48, Daniel J Weisdorf2. 1. Department of Stem Cell Transplantation, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX. 2. University of Minnesota, Minneapolis, MN. 3. Center for International Blood and Marrow Transplant Research (CIBMTR), Medical College of Wisconsin, Milwaukee, WI. 4. Division of Biostatistics, Institute for Health and Equity, Medical College of Wisconsin, Milwaukee, WI. 5. CIBMTR, National Marrow Donor Program/Be the Match, Minneapolis, MN. 6. Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota Medical Center, Minneapolis, MN. 7. Utah Blood and Marrow Transplant Program, Salt Lake City, UT. 8. Department of Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center, Tampa, FL. 9. Division of Hematology, Oncology and Blood & Marrow Transplantation, Children's Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, CA. 10. Division of Hematology-Oncology, Indiana University School of Medicine, Indianapolis, IN. 11. Department of Hematology Oncology and Bone Marrow Transplantation, The Children's Mercy Hospitals and Clinics, Kansas City, MO. 12. New York University Langone Medical Center, New York, NY. 13. Department of Oncology, King Faisal Specialist Hospital Center & Research, Riyadh, Saudi Arabia. 14. Division of Hematologic Malignancies, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA. 15. Department of Pathology and Laboratory Medicine, Baylor University Medical Center, Dallas, TX. 16. Blood and Marrow Transplant Program and Host Defense Program, Divisions of Hematology/Oncology/Bone Marrow Transplant and Infectious Diseases, Nationwide Children's Hospital, Columbus, OH. 17. The Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE. 18. Royal Melbourne Hospital City Campus, Victoria, Australia. 19. Division of Hematology/Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI. 20. Tom Baker Cancer Center, Calgary, Alberta, Canada. 21. Blood and Marrow Transplant Program, Massachusetts General Hospital, Boston, MA. 22. Oregon Health and Science University, Portland, OR. 23. Hematology Research Centre, Division of Experimental Medicine, Department of Medicine, Imperial College London, London, United Kingdom. 24. Hematolgic Malignancies & Bone Marrow Transplant, Department of Medical Oncology, New York Presbyterian Hospital/Weill Cornell Medical Center, New York, NY. 25. Division of Hematology/Oncology/Bone Marrow Transplantation, Department of Medicine, University of Wisconsin Hospital and Clinics, Madison, WI. 26. Markey Cancer Center, University of Kentucky, Lexington, KY. 27. Division of Hematology/Bone Marrow Transplantation, Mayo Clinic, Rochester, MN. 28. Division of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan. 29. Division of Clinical Hematology, Hospital de la Santa Creu I Sant Pau, Barcelona, Spain. 30. Blood & Marrow Transplant Program, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH. 31. Adult Bone Marrow Transplant, University Hospitals Bristol National Health Service Trust, Bristol, United Kingdom. 32. Translational Cell Therapy Research, Clintec, Karolinska Institutet, Stockholm, Sweden. 33. Centre for Clinical Research Sormland, Uppsala University, Uppsala, Sweden. 34. Blood and Marrow Transplantation Program, Division of Hematology/Oncology, Department of Internal Medicine, The University of Michigan Medical School, Ann Arbor, MI. 35. Department of Hematology/Oncology, Hospital Infantil Universitario Nino Jesus, Madrid, Spain. 36. Blood and Cancer Centre, Starship Children's Hospital, Auckland, New Zealand. 37. Division of Hematology, Ohio State University, Columbus, OH. 38. Division of Pediatric Hematology/Oncology, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN. 39. University Hospital Leuven and Katholieke Universiteit Leuven, Leuven, Belgium. 40. Department of Hematology & Oncology, National Cancer Research Center East, Chiba, Japan. 41. Department of Pediatric Hematology, Oncology and Bone Marrow Transplant, British Columbia's Children's Hospital, The University of British Columbia, Vancouver, BC, Canada. 42. The Blood and Marrow Transplant Group of Georgia, Northside Hospital, Atlanta, GA. 43. Department of Medicine, University of Calgary, Calgary, Alberta, Canada. 44. Hokkaido University Hospital, Sapporo, Japan. 45. Department of Hematology/Oncology, Isala Clinic, Zwolle, The Netherlands. 46. Division of Bone Marrow Transplant, Seattle Cancer Care Alliance, Seattle, WA. 47. Blood & Marrow Transplantation Program, Division of Hematology/Oncology, Department of Medicine, Greenebaum Comprehensive Cancer Center, University of Maryland, Baltimore, MD. 48. Department of Hematology, Centre Hospitalier Universitaire Grenoble Alpes, Grenoble, France.
Abstract
PURPOSE: There is no consensus on the best choice of an alternative donor (umbilical cord blood [UCB], haploidentical, one-antigen mismatched [7/8]-bone marrow [BM], or 7/8-peripheral blood [PB]) for hematopoietic cell transplantation (HCT) for patients lacking an HLA-matched related or unrelated donor. METHODS: We report composite end points of graft-versus-host disease (GVHD)-free relapse-free survival (GRFS) and chronic GVHD (cGVHD)-free relapse-free survival (CRFS) in 2,198 patients who underwent UCB (n = 838), haploidentical (n = 159), 7/8-BM (n = 241), or 7/8-PB (n = 960) HCT. All groups were divided by myeloablative conditioning (MAC) intensity or reduced intensity conditioning (RIC), except haploidentical group in which most received RIC. To account for multiple testing, P < .0071 in multivariable analysis and P < .00025 in direct pairwise comparisons were considered statistically significant. RESULTS: In multivariable analysis, haploidentical group had the best GRFS, CRFS, and overall survival (OS). In the direct pairwise comparison of other groups, among those who received MAC, there was no difference in GRFS or CRFS among UCB, 7/8-BM, and 7/8-PB with serotherapy (alemtuzumab or antithymocyte globulin) groups. In contrast, the 7/8-PB without serotherapy group had significantly inferior GRFS, higher cGVHD, and a trend toward worse CRFS (hazard ratio [HR], 1.38; 95% CI, 1.13 to 1.69; P = .002) than the 7/8-BM group and higher cGVHD and trend toward inferior CRFS (HR, 1.36; 95% CI, 1.14 to 1.63; P = .0006) than the UCB group. Among patients with RIC, all groups had significantly inferior GRFS and CRFS compared with the haploidentical group. CONCLUSION: Recognizing the limitations of a registry retrospective analysis and the possibility of center selection bias in choosing donors, our data support the use of UCB, 7/8-BM, or 7/8-PB (with serotherapy) grafts for patients undergoing MAC HCT and haploidentical grafts for patients undergoing RIC HCT. The haploidentical group had the best GRFS, CRFS, and OS of all groups.
PURPOSE: There is no consensus on the best choice of an alternative donor (umbilical cord blood [UCB], haploidentical, one-antigen mismatched [7/8]-bone marrow [BM], or 7/8-peripheral blood [PB]) for hematopoietic cell transplantation (HCT) for patients lacking an HLA-matched related or unrelated donor. METHODS: We report composite end points of graft-versus-host disease (GVHD)-free relapse-free survival (GRFS) and chronic GVHD (cGVHD)-free relapse-free survival (CRFS) in 2,198 patients who underwent UCB (n = 838), haploidentical (n = 159), 7/8-BM (n = 241), or 7/8-PB (n = 960) HCT. All groups were divided by myeloablative conditioning (MAC) intensity or reduced intensity conditioning (RIC), except haploidentical group in which most received RIC. To account for multiple testing, P < .0071 in multivariable analysis and P < .00025 in direct pairwise comparisons were considered statistically significant. RESULTS: In multivariable analysis, haploidentical group had the best GRFS, CRFS, and overall survival (OS). In the direct pairwise comparison of other groups, among those who received MAC, there was no difference in GRFS or CRFS among UCB, 7/8-BM, and 7/8-PB with serotherapy (alemtuzumab or antithymocyte globulin) groups. In contrast, the 7/8-PB without serotherapy group had significantly inferior GRFS, higher cGVHD, and a trend toward worse CRFS (hazard ratio [HR], 1.38; 95% CI, 1.13 to 1.69; P = .002) than the 7/8-BM group and higher cGVHD and trend toward inferior CRFS (HR, 1.36; 95% CI, 1.14 to 1.63; P = .0006) than the UCB group. Among patients with RIC, all groups had significantly inferior GRFS and CRFS compared with the haploidentical group. CONCLUSION: Recognizing the limitations of a registry retrospective analysis and the possibility of center selection bias in choosing donors, our data support the use of UCB, 7/8-BM, or 7/8-PB (with serotherapy) grafts for patients undergoing MAC HCT and haploidentical grafts for patients undergoing RIC HCT. The haploidentical group had the best GRFS, CRFS, and OS of all groups.
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