Effect of the Thiotepa Dose in the TBF Conditioning Regimen in Patients Undergoing Allogeneic Stem Cell Transplantation for Acute Myeloid Leukemia in Complete Remission: A Report From the EBMT Acute Leukemia Working Party |
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| Affiliation: | 1. Clinical Research Division, Program in Immunology, Fred Hutchison Cancer Research Centre, Seattle, Washington;2. Eurocord, Hopital Saint Louis—EA3518, Paris, France;3. Department of Stem Cell Transplant and Immunotherapy, Hospital Universitario La Fe, Valencia, Spain;4. Department of Stem Cell Transplant and Immunotherapy, Haut-Lévêque, Bordeaux, France;5. Department of Stem Cell Transplant and Immunotherapy, Erasmus MC-Daniel den Hoed Cancer Centre, Rotterdam, The Netherlands;6. Department of Stem Cell Transplant and Immunotherapy, Paoli Calmettes, Marseille, France;7. Department of Stem Cell Transplant and Immunotherapy, Hospital Santa Creu i Sant Pau, Barcelona, Spain;8. Department of Stem Cell Transplant and Immunotherapy, Service d''Hematologie, Centre Leon Berard, Lyon, France;9. Department of Stem Cell Transplant and Immunotherapy, Azienda Ospedaliero Universitaria Meyer—Ospedale di Careggi, Firenze, Italy;10. Centre de Thérapie Cellulaire, Département de Biologie du Cancer, Institut Paoli-Calmettes, & Inserm CBT-1409, Aix-Marseille Université, Marseille, France;11. Haematology and Bone Marrow Transplant Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy;1. Universidade Federal de São Paulo, São Paulo, Brazil;2. Hospital Sírio Libanês, São Paulo, Brazil;3. Hospital e Maternidade São Camilo da Pompéia. São Paulo, Brazil;4. Instituto Brasileiro de Controle do Câncer (IBCC). São Paulo, Brazil;5. Hospital Israelita Albert Einstein, São Paulo, Brazil;6. A.C. Camargo Cancer Center, São Paulo, Brazil;1. University of Texas, MD Anderson Cancer Center, Houston, Texas;2. National Cancer Institute, National Institutes of Health, Bethesda, Maryland;3. Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin;4. Division of Biostatistics, Institute for Health and Society, Medical College of Wisconsin, Milwaukee, Wisconsin;5. Division of Hematology, Oncology and Blood & Marrow Transplantation, Children''s Hospital Los Angeles, Los Angeles, California;6. University of Southern California Keck School of Medicine, Los Angeles, California;7. Department of Oncology, King Faisal Specialist Hospital Center & Research, Riyadh, Saudi Arabia;8. Department of Hematology, Inselspital, Bern University Hospital, Bern, Switzerland;9. Department of Blood and Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, Florida;10. Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia;11. Division of Hematology, Oncology and Blood & Marrow Transplantation, University of Iowa Hospitals and Clinics, Iowa City, Iowa;12. The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland;13. Department of Hematologic Oncology and Blood Disorders, Levine Cancer Institute, Atrium Health, Charlotte, North Carolina;14. Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, California;15. Department of Medicine, Division of Hematology/Oncology, Loyola University Chicago-Stritch School of Medicine, Maywood, Illinois;16. Division of Hematology, Mayo Clinic, Rochester, Minnesota;17. Osborn Hematopoietic Malignancy and Transplantation Program, West Virginia University, Morgantown, West Virginia;18. Divison of Clinical Hematology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain;19. Georgetown University Hospital, Washington, DC;20. Division of Hematology/Oncology, University Florida College of Medicine, Gainesville, Florida;21. Hematology Department, Institut Català d''Oncologia-Hospitalet, Barcelona, Spain;22. Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York;23. Dana Farber Cancer Institute, Boston, Massachusetts;24. Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee;25. Department of Haematology and Oncology, Dokkyo Medical University, Mibu, Tochigi, Japan;26. Division of Bone Marrow Transplant, Seattle Cancer Care Alliance, Seattle, Washington;27. Blood & Marrow Transplantation Program, Division of Hematology/Oncology, Department of Medicine, Greenebaum Comprehensive Cancer Center, University of Maryland, Baltimore, Maryland;28. Division of Hematology and Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin |
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| Abstract: | BackgroundAllogeneic stem cell transplantation is a potentially curative therapy for patients with acute myeloid leukemia (AML) after achieving complete remission (CR). The aim of this study is to evaluate the optimal dose of thiotepa, administered as part of the thiotepa-busulfan-fludarabine (TBF) conditioning regimen for allogeneic stem cell transplantation in adults with AML in CR.Patients and MethodsIn a retrospective multicenter analysis, we identified 240 patients allotransplanted from matched related or unrelated donors or T replete haplo-identical donors. We compared the transplantation outcomes of patients who received 5 mg/kg thiotepa and 2 days of intravenous busulfan at 6.4 mg/kg (T1B2F) versus those who received 10 mg/kg thiotepa with 2 days of intravenous busulfan at 6.4 mg/kg (T2B2F). The median follow-up was 20 months.ResultsOn univariate analysis, the incidence of acute graft versus host disease (GVHD) grade II to IV was significantly lower in the T1B2F group (19%) versus 32% in the T2B2F group (P = .029). This result was confirmed on multivariate analysis; acute GVHD was higher for patients receiving T2B2F (hazard ratio, 2.22; P = .024). No significant change in non-relapse mortality, progression-free survival, or overall survival was observed between the 2 groups.ConclusionT2B2F is associated with a higher incidence of acute GVHD compared with T1B2F. These results suggest that a lower dose-intensity of thiotepa and busulfan in the TBF regimen may yield better results in patients with AML in CR. |
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| Keywords: | Acute myloid leukemia Complete remission Overall survival (OS) Thiotepa-busulfan-fludarabine Transplant outcomes |
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