Guru Subramanian Guru Murthy1, Soyoung Kim2,3, Zhen-Huan Hu2, Noel Estrada-Merly2, Muhammad Bilal Abid1,4, Mahmoud Aljurf5, Ulrike Bacher6, Sherif M Badawy7,8, Amer Beitinjaneh9, Chris Bredeson10, Jean-Yves Cahn11, Jan Cerny12, Miguel Angel Diaz Perez13, Nosha Farhadfar14, Robert Peter Gale15, Siddhartha Ganguly16, Usama Gergis17, Gerhard C Hildebrandt18, Michael R Grunwald19, Shahrukh Hashmi20,21, Nasheed M Hossain22, Matt Kalaycio23, Rammurti T Kamble24, Mohamed A Kharfan-Dabaja25, Betty Ky Hamilton23, Hillard M Lazarus26, Jane Liesveld27, Mark Litzow28, David I Marks29, Hemant S Murthy25, Sunita Nathan30, Aziz Nazha31, Taiga Nishihori32, Sagar S Patel33, Attaphol Pawarode34, David Rizzieri35, Bipin Savani36, Sachiko Seo37, Melhem Solh38, Celalettin Ustun39, Marjolein van der Poel40, Leo F Verdonck41, Ravi Vij42, Baldeep Wirk43, Betul Oran44, Ryotaro Nakamura45, Bart Scott46, Wael Saber2. 1. Division of Hematology and Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee. 2. Department of Medicine, Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee. 3. Division of Biostatistics, Institute for Health and Equity, Medical College of Wisconsin, Milwaukee. 4. Division of Infectious Diseases, Department of Medicine, Medical College of Wisconsin, Milwaukee. 5. Department of Oncology, King Faisal Specialist Hospital Center and Research, Riyadh, Saudi Arabia. 6. Department of Hematology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. 7. Division of Hematology, Oncology, and Stem Cell Transplant, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois. 8. Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois. 9. Division of Transplantation and Cellular Therapy, University of Miami, Miami, Florida. 10. Ottawa Hospital Transplant and Cellular Therapy Program, The Ottawa Hospital, Ottawa, Ontario, Canada. 11. Department of Hematology, CHU Grenoble Alpes, Université Grenoble Alpes, Grenoble, France. 12. Division of Hematology-Oncology, Department of Medicine, University of Massachusetts Medical Center, Worcester. 13. Department of Hematology and Oncology, Hospital Infantil Universitario Niño Jesus, Madrid, Spain. 14. Division of Hematology and Oncology, University of Florida College of Medicine, Gainesville. 15. Haematology Research Centre, Department of Immunology and Inflammation, Imperial College London, London, UK. 16. Division of Hematological Malignancy and Cellular Therapeutics, University of Kansas Health System, Kansas City. 17. Division of Hematological Malignancies, Department of Medical Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania. 18. Markey Cancer Center, University of Kentucky College of Medicine, Lexington. 19. Department of Hematologic Oncology and Blood Disorders, Levine Cancer Institute, Atrium Health, Charlotte, North Carolina. 20. Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota. 21. Department of Medicine, Sheikh Shakhbout Medical City, Abu Dhabi, United Arab Emirates. 22. Division of Hematology and Oncology, Stem Cell Transplant Program, Department of Medicine, Loyola University Chicago Stritch School of Medicine, Maywood, Illinois. 23. Blood and Marrow Transplant Program, Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio. 24. Divsion of Hematology and Oncology, Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas. 25. Division of Hematology-Oncology, Blood and Marrow Transplantation Program, Mayo Clinic, Jacksonville, Florida. 26. Department of Medicine, University Hospitals Cleveland Medical Center, Case Western Reserve University, Cleveland, Ohio. 27. Department of Medicine, University of Rochester Medical Center, Rochester, New York. 28. Division of Hematology and Transplant Center, Mayo Clinic Rochester, Rochester, Minnesota. 29. Adult Bone Marrow Transplant, University Hospitals Bristol National Health Service Trust, Bristol, UK. 30. Section of Bone Marrow Transplant and Cell Therapy, Rush University Medical Center, Chicago, Illinois. 31. Cleveland Clinic Foundation, Cleveland, Ohio. 32. Department of Blood and Marrow Transplant and Cellular Immunotherapy Moffitt Cancer Center, Tampa, Florida. 33. Blood and Marrow Transplant Program, Huntsman Cancer Institute, University of Utah, Salt Lake City. 34. Blood and Marrow Transplantation Program, Division of Hematology and Oncology, Department of Internal Medicine, The University of Michigan Medical School, Ann Arbor. 35. Division of Hematologic Malignancies and Cellular Therapy, Duke University, Durham, North Carolina. 36. Division of Hematology and Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee. 37. Department of Hematology and Oncology, Dokkyo Medical University, Tochigi, Japan. 38. Blood and Marrow Transplant Group of Georgia, Northside Hospital, Atlanta. 39. Division of Hematology, Oncology, and Cell Therapy, Rush University, Chicago, Illinois. 40. Maastricht University Medical Center, Maastricht, the Netherlands. 41. Department of Hematology and Oncology, Isala Clinic, Zwolle, the Netherlands. 42. Division of Hematology and Oncology, Washington University School of Medicine, St Louis, Missouri. 43. Bone Marrow Transplant Program, Penn State Cancer Institute, Hershey, Pennsylvania. 44. Division of Cancer Medicine, Department of Stem Cell Transplantation, The University of Texas MD Anderson Cancer Center, Houston. 45. Department of Hematology & Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, California. 46. Fred Hutchinson Cancer Research Center, Seattle, Washington.
Abstract
IMPORTANCE: Matched sibling donors (MSDs) are preferred for allogeneic hematopoietic cell transplantation (allo-HCT) in myelodysplastic syndrome even if they are older. However, whether older MSDs or younger human leukocyte antigen-matched unrelated donors (MUDs) are associated with better outcomes remains unclear. OBJECTIVE: To investigate whether allo-HCT for myelodysplastic syndrome using younger MUDs would be associated with improved disease-free survival and less relapse compared with older MSDs. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study assessed data reported to the Center for International Blood and Marrow Transplant Research database from 1761 adults 50 years or older with myelodysplastic syndrome who underwent allo-HCT using an older MSD or younger MUD between January 1, 2011, and December 31, 2017, with a median follow-up of 48 months. Data analysis was performed from January 8, 2019, to December 30, 2020. INTERVENTIONS/EXPOSURES: Allo-HCT from an older MSD (donor age ≥50 years) or a younger MUD (donor age ≤35 years). MAIN OUTCOMES AND MEASURES: The primary outcome was disease-free survival. Secondary outcomes were overall survival, relapse, nonrelapse mortality, acute graft-vs-host disease (GVHD), chronic GVHD, and GVHD-free relapse-free survival. RESULTS: Of 1761 patients (1162 [66%] male; median [range] age, 64.9 [50.2-77.6] years in the MSD cohort and 66.5 [50.4-80.9] years in MUD cohort), 646 underwent allo-HCT with an older MSD and 1115 with a younger MUD. In multivariable analysis, the rate of disease-free survival was significantly lower in allo-HCTs with older MSDs compared with younger MUDs (hazard ratio [HR], 1.17; 95% CI, 1.02-1.34; P = .02), whereas the difference in overall survival rate of allo-HCT with younger MUDs vs older MSDs was not statistically significant (HR, 1.13; 95% CI, 0.98-1.29; P = .07). Allo-HCT with older MSDs was associated with significantly higher relapse (HR, 1.62; 95% CI, 1.32-1.97; P < .001), lower nonrelapse mortality (HR, 0.76; 95% CI, 0.59-0.96; P = .02), lower acute GVHD (HR, 0.52; 95% CI, 0.42-0.65; P < .001), chronic GVHD (HR, 0.77; 95% CI, 0.64-0.92; P = .005), and a lower rate of GVHD-free relapse-free survival beyond 12 months after allo-HCT (HR, 1.42; 95% CI, 1.02-1.98; P = .04). CONCLUSIONS AND RELEVANCE: This cohort study found higher disease-free survival and lower relapse for allo-HCT in myelodysplastic syndrome using younger MUDs compared with older MSDs. The risk of nonrelapse mortality and GVHD was lower with older MSDs. These results suggest that the use of younger MUDs should be considered in the donor selection algorithm for myelodysplastic syndrome, in which it is pivotal to minimize relapse given limited treatment options for managing relapsed disease.
IMPORTANCE: Matched sibling donors (MSDs) are preferred for allogeneic hematopoietic cell transplantation (allo-HCT) in myelodysplastic syndrome even if they are older. However, whether older MSDs or younger human leukocyte antigen-matched unrelated donors (MUDs) are associated with better outcomes remains unclear. OBJECTIVE: To investigate whether allo-HCT for myelodysplastic syndrome using younger MUDs would be associated with improved disease-free survival and less relapse compared with older MSDs. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study assessed data reported to the Center for International Blood and Marrow Transplant Research database from 1761 adults 50 years or older with myelodysplastic syndrome who underwent allo-HCT using an older MSD or younger MUD between January 1, 2011, and December 31, 2017, with a median follow-up of 48 months. Data analysis was performed from January 8, 2019, to December 30, 2020. INTERVENTIONS/EXPOSURES: Allo-HCT from an older MSD (donor age ≥50 years) or a younger MUD (donor age ≤35 years). MAIN OUTCOMES AND MEASURES: The primary outcome was disease-free survival. Secondary outcomes were overall survival, relapse, nonrelapse mortality, acute graft-vs-host disease (GVHD), chronic GVHD, and GVHD-free relapse-free survival. RESULTS: Of 1761 patients (1162 [66%] male; median [range] age, 64.9 [50.2-77.6] years in the MSD cohort and 66.5 [50.4-80.9] years in MUD cohort), 646 underwent allo-HCT with an older MSD and 1115 with a younger MUD. In multivariable analysis, the rate of disease-free survival was significantly lower in allo-HCTs with older MSDs compared with younger MUDs (hazard ratio [HR], 1.17; 95% CI, 1.02-1.34; P = .02), whereas the difference in overall survival rate of allo-HCT with younger MUDs vs older MSDs was not statistically significant (HR, 1.13; 95% CI, 0.98-1.29; P = .07). Allo-HCT with older MSDs was associated with significantly higher relapse (HR, 1.62; 95% CI, 1.32-1.97; P < .001), lower nonrelapse mortality (HR, 0.76; 95% CI, 0.59-0.96; P = .02), lower acute GVHD (HR, 0.52; 95% CI, 0.42-0.65; P < .001), chronic GVHD (HR, 0.77; 95% CI, 0.64-0.92; P = .005), and a lower rate of GVHD-free relapse-free survival beyond 12 months after allo-HCT (HR, 1.42; 95% CI, 1.02-1.98; P = .04). CONCLUSIONS AND RELEVANCE: This cohort study found higher disease-free survival and lower relapse for allo-HCT in myelodysplastic syndrome using younger MUDs compared with older MSDs. The risk of nonrelapse mortality and GVHD was lower with older MSDs. These results suggest that the use of younger MUDs should be considered in the donor selection algorithm for myelodysplastic syndrome, in which it is pivotal to minimize relapse given limited treatment options for managing relapsed disease.