Impact of T Cell Dose on Outcome of T Cell-Replete HLA-Matched Allogeneic Peripheral Blood Stem Cell Transplantation |
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| Authors: | Ayman Saad Lawrence Lamb Tao Wang Michael T. Hemmer Stephen Spellman Daniel Couriel Amin Alousi Joseph Pidala Hisham Abdel-Azim Vaibhav Agrawal Mahmoud Aljurf Amer M. Beitinjaneh Vijaya Raj Bhatt David Buchbinder Michael Byrne Jean-Yves Cahn Mitchell Cairo Paul Castillo Shahrukh Hashmi |
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| Affiliation: | 3. Division of Biostatistics, Institute for Health and Equity, Medical College of Wisconsin, Milwaukee, Wisconsin;4. Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin;5. Center for International Blood and Marrow Transplant Research, National Marrow Donor Program/Be the Match, Minneapolis, Minnesota;6. Utah Blood and Marrow Transplant Program, Salt Lake City, Utah;7. Department of Stem Cell Transplantation, Division of Cancer Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, Texas;8. Department of Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center, Tampa, Florida;9. Division of Hematology, Oncology and Blood and Marrow Transplantation, Children''s Hospital of Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, California;10. Division of Hematology-Oncology, Indiana University School of Medicine, Indianapolis, Indiana;11. Oncology Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia;12. University of Miami, Miami, Florida;13. The Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, Nebraska;14. Division of Pediatric Hematology, Children''s Hospital of Orange County, Orange, California;15. Division of Hematology/Oncology, Vanderbilt University Medical Center, Nashville, Tennessee;16. Department of Hematology, CHU Grenoble Alpes, Grenoble, France;17. Division of Pediatric Hematology, Oncology, and Stem Cell Transplantation, Department of Pediatrics, New York Medical College, New York, New York;18. UF Health Shands Children''s Hospital, Gainesville, Florida;19. Division of Hematology/Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin;20. Department of Hematology/Oncology, Hospital Infantil Universitario Nino Jesus, Madrid, Spain;21. Henry Ford Hospital Bone Marrow Transplant Program, Detroit, Michigan;22. The National Hospital, Oslo, Denmark;23. Children''s Hospital at TriStar Centennial and Sarah Cannon Research Institute, Nashville, Tennessee;24. Division of Cancer Epidemiology & Genetics, Clinical Genetics Branch, National Cancer Institute, Rockville, Maryland;25. Consultant at Lu Daopei Hospital, Beijing, China;26. Hematology Research Center, Division of Experimental Medicine, Department of Medicine, Imperial College London, London, United Kingdom;27. Division of Transfusion Medicine, Mayo Clinic, Rochester, Minnesota;28. Hematologic Malignancies & Bone Marrow Transplant, Department of Medical Oncology, New York Presbyterian Hospital/Weill Cornell Medical Center, New York, New York;29. Blood & Marrow Transplant Program, Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio;30. Division of Hematology/Oncology/Bone Marrow Transplantation, Department of Medicine, University of Wisconsin Hospital and Clinics, Madison, Wisconsin;31. Markey Cancer Center, University of Kentucky, Lexington, Kentucky;32. Division of Hematology and Oncology, Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas;33. Osborn Hematopoietic Malignancy and Transplantation Program, West Virginia University, Morgantown, West Virginia;34. Division of Bone Marrow Transplant and Immune Deficiency, Cincinnati Children''s Hospital Medical Center, Cincinnati, Ohio;35. University of Minnesota Blood and Marrow Transplant Program, Pediatrics, Minneapolis, Minnesota;36. Adult Bone Marrow Transplant, University Hospitals Bristol NHS Trust, Bristol, United Kingdom;37. Division of Clinical Hematology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain;38. Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden;39. Centre for Clinical Research Sormland, Uppsala University, Uppsala, Sweden;40. Blood and Marrow Transplant Program, Cleveland Clinic Foundation, Cleveland, Ohio;41. Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia;42. Department of Pediatric Hematology, Oncology, Blood and Marrow Transplantation, Nationwide Children''s Hospital, Columbus, Ohio;43. Blood and Marrow Transplantation Program and Columbia Center for Translational Immunobiology, Columbia University Medical Center, New York, New York;44. Translational Cell Therapy Research, Karolinska Institute, Stockholm, Sweden;45. Department of Hematology, Academische Ziekenhuis, Maastricht, Netherlands;46. Department of Pediatric Hematology, Oncology and Bone Marrow Transplant, British Columbia''s Children''s Hospital, The University of British Columbia, Vancouver, Britich Columbia, Canada;47. Department of Hematology and Oncology, Dokkyo Medical University, Tochigi, Japan;48. Memorial Sloan Kettering Cancer Center, New York, New York;49. The Blood and Marrow Transplant Group of Georgia, Northside Hospital, Atlanta, Georgia;50. Hokkaido University Hospital, Sapporo, Japan;51. Department of Hematology, Hospital Clinic, University of Barcelona, IDIBAPS, and Josep Carreras Institute of Research, Barcelona, Spain;52. Department of Hematology/Oncology, Isala Clinic, Zwolle, The Netherlands;53. Division of Hematology and Oncology, Washington University School of Medicine, St Louis, Missouri;54. Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia;55. Division of Bone Marrow Transplant, Seattle Cancer Care Alliance, Seattle, Washington;56. Blood & Marrow Transplantation Program, Division of Hematology/Oncology, Department of Medicine, Greenebaum Comprehensive Cancer Center, University of Maryland, Baltimore, Maryland;57. Division of Hematology/Oncology and HSCT, Center for Cancer and Blood Disorders, Children''s Hospital/Louisiana State University Medical Center, New Orleans, Louisiana;58. Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota Medical Center, Minneapolis, Minnesota;59. Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota;1. Division of Hematology, The Ohio State University, Columbus, Ohio;2. University of Alabama at Birmingham, Birmingham, Alabama;3. Division of Biostatistics, Institute for Health and Equity, Medical College of Wisconsin, Milwaukee, Wisconsin;4. Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin;5. Center for International Blood and Marrow Transplant Research, National Marrow Donor Program/Be the Match, Minneapolis, Minnesota;6. Utah Blood and Marrow Transplant Program, Salt Lake City, Utah;7. Department of Stem Cell Transplantation, Division of Cancer Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, Texas;8. Department of Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center, Tampa, Florida;9. Division of Hematology, Oncology and Blood and Marrow Transplantation, Children''s Hospital of Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, California;10. Division of Hematology-Oncology, Indiana University School of Medicine, Indianapolis, Indiana;11. Oncology Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia;12. University of Miami, Miami, Florida;13. The Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, Nebraska;14. Division of Pediatric Hematology, Children''s Hospital of Orange County, Orange, California;15. Division of Hematology/Oncology, Vanderbilt University Medical Center, Nashville, Tennessee;16. Department of Hematology, CHU Grenoble Alpes, Grenoble, France;17. Division of Pediatric Hematology, Oncology, and Stem Cell Transplantation, Department of Pediatrics, New York Medical College, New York, New York;18. UF Health Shands Children''s Hospital, Gainesville, Florida;19. Division of Hematology/Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin;20. Department of Hematology/Oncology, Hospital Infantil Universitario Nino Jesus, Madrid, Spain;21. Henry Ford Hospital Bone Marrow Transplant Program, Detroit, Michigan;22. The National Hospital, Oslo, Denmark;23. Children''s Hospital at TriStar Centennial and Sarah Cannon Research Institute, Nashville, Tennessee;24. Division of Cancer Epidemiology & Genetics, Clinical Genetics Branch, National Cancer Institute, Rockville, Maryland;25. Consultant at Lu Daopei Hospital, Beijing, China;26. Hematology Research Center, Division of Experimental Medicine, Department of Medicine, Imperial College London, London, United Kingdom;27. Division of Transfusion Medicine, Mayo Clinic, Rochester, Minnesota;28. Hematologic Malignancies & Bone Marrow Transplant, Department of Medical Oncology, New York Presbyterian Hospital/Weill Cornell Medical Center, New York, New York;29. Blood & Marrow Transplant Program, Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio;30. Division of Hematology/Oncology/Bone Marrow Transplantation, Department of Medicine, University of Wisconsin Hospital and Clinics, Madison, Wisconsin;31. Markey Cancer Center, University of Kentucky, Lexington, Kentucky;32. Division of Hematology and Oncology, Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas;33. Osborn Hematopoietic Malignancy and Transplantation Program, West Virginia University, Morgantown, West Virginia;34. Division of Bone Marrow Transplant and Immune Deficiency, Cincinnati Children''s Hospital Medical Center, Cincinnati, Ohio;35. University of Minnesota Blood and Marrow Transplant Program, Pediatrics, Minneapolis, Minnesota;36. Adult Bone Marrow Transplant, University Hospitals Bristol NHS Trust, Bristol, United Kingdom;37. Division of Clinical Hematology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain;38. Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden;39. Centre for Clinical Research Sormland, Uppsala University, Uppsala, Sweden;40. Blood and Marrow Transplant Program, Cleveland Clinic Foundation, Cleveland, Ohio;41. Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia;42. Department of Pediatric Hematology, Oncology, Blood and Marrow Transplantation, Nationwide Children''s Hospital, Columbus, Ohio;43. Blood and Marrow Transplantation Program and Columbia Center for Translational Immunobiology, Columbia University Medical Center, New York, New York;44. Translational Cell Therapy Research, Karolinska Institute, Stockholm, Sweden;45. Department of Hematology, Academische Ziekenhuis, Maastricht, Netherlands;46. Department of Pediatric Hematology, Oncology and Bone Marrow Transplant, British Columbia''s Children''s Hospital, The University of British Columbia, Vancouver, Britich Columbia, Canada;47. Department of Hematology and Oncology, Dokkyo Medical University, Tochigi, Japan;48. Memorial Sloan Kettering Cancer Center, New York, New York;49. The Blood and Marrow Transplant Group of Georgia, Northside Hospital, Atlanta, Georgia;50. Hokkaido University Hospital, Sapporo, Japan;51. Department of Hematology, Hospital Clinic, University of Barcelona, IDIBAPS, and Josep Carreras Institute of Research, Barcelona, Spain;52. Department of Hematology/Oncology, Isala Clinic, Zwolle, The Netherlands;53. Division of Hematology and Oncology, Washington University School of Medicine, St Louis, Missouri;54. Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia;55. Division of Bone Marrow Transplant, Seattle Cancer Care Alliance, Seattle, Washington;56. Blood & Marrow Transplantation Program, Division of Hematology/Oncology, Department of Medicine, Greenebaum Comprehensive Cancer Center, University of Maryland, Baltimore, Maryland;57. Division of Hematology/Oncology and HSCT, Center for Cancer and Blood Disorders, Children''s Hospital/Louisiana State University Medical Center, New Orleans, Louisiana;58. Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota Medical Center, Minneapolis, Minnesota;59. Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota |
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| Abstract: | Data on whether the T cell dose of allogeneic peripheral blood stem cell (PBSC) products influences transplantation outcomes are conflicting. Using the Center for International Blood and Marrow Transplant Research database, we identified 2736 adult patients who underwent first allogeneic PBSC transplantation for acute leukemia or myelodysplastic syndrome between 2008 and 2014 using an HLA-matched sibling donor (MSD) or an 8/8-matched unrelated donor (MUD). We excluded ex vivo and in vivo T cell-depleted transplantations. Correlative analysis was performed between CD3+ T cell dose and the risk of graft-versus-host-disease (GVHD), relapse, nonrelapse mortality (NRM), disease-free survival (DFS), and overall survival (OS). Using maximum likelihood estimation, we identified CD3+ T cell dose cutoff that separated the risk of acute GVHD (aGVHD) grade II-IV in both the MSD and MUD groups. A CD3+ T cell dose cutoff of 14 × 107 cells/kg identified MSD/low CD3+ (n = 223) and MSD/high CD3+ (n = 1214), and a dose of 15 × 107 cells/kg identified MUD/low CD3+ (n = 197) and MUD/high CD3+ (n = 1102). On univariate analysis, the MSD/high CD3+ group had a higher cumulative incidence of day +100 aGVHD grade II-IV compared with the MSD/low CD3+ group (33% versus 25%; P = .009). There were no differences between the 2 groups in engraftment rate, risk of aGVHD grade III-IV or chronic GVHD (cGVHD), NRM, relapse, DFS, or OS. The MUD/high CD3+ group had a higher cumulative incidence of day +100 aGVHD grade II-IV compared with the MUD/low CD3+ group (49% versus 41%; P = .04). There were no differences between the 2 groups in engraftment rate, risk of severe aGVHD or cGVHD, NRM, relapse, DFS, or OS. Multivariate analysis of the MSD and MUD groups failed to show an association between CD3+ T cell dose and the risk of either aGVHD grade II-IV (P = .10 and .07, respectively) or cGVHD (P = .80 and .30, respectively). Subanalysis of CD4+ T cells, CD8+ T cells, and CD4+/CD8+ ratio failed to identify cutoff values predictive of transplantation outcomes; however, using the log-rank test, the sample size was suboptimal for identifying a difference at this cutoff cell dose. In this registry study, the CD3+ T cell dose of PBSC products did not influence the risk of aGVHD or cGVHD or other transplantation outcomes when using an MSD or an 8/8-matched MUD. Subset analyses of CD4+ and CD8+ T cell doses were not possible given our small sample size. |
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| Keywords: | Correspondence and reprint requests: Mukta Arora, MD, University of Minnesota Medical Center, Division of Hematology, Oncology and Transplantation, Minneapolis, 420 Delaware St, SE Minneapolis, MN 55455. T cell GVHD dose Allogeneic Transplantation |
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