Tomas Radivoyevitch1, Robert M Dean2, Bronwen E Shaw3, Ruta Brazauskas4, Heather R Tecca5, Remco J Molenaar6, Minoo Battiwalla7, Bipin N Savani8, Mary E D Flowers9, Kenneth R Cooke10, Betty K Hamilton2, Matt Kalaycio2, Jaroslaw P Maciejewski2, Ibrahim Ahmed11, Görgün Akpek12, Ashish Bajel13, David Buchbinder14, Jean-Yves Cahn15, Anita D'Souza5, Andrew Daly16, Zachariah DeFilipp17, Siddhartha Ganguly18, Mehdi Hamadani5, Robert J Hayashi19, Peiman Hematti20, Yoshihiro Inamoto21, Nandita Khera22, Tamila Kindwall-Keller23, Heather Landau24, Hillard Lazarus25, Navneet S Majhail2, David I Marks26, Richard F Olsson27, Sachiko Seo28, Amir Steinberg29, Basem M William30, Baldeep Wirk31, Jean A Yared32, Mahmoud Aljurf33, Muneer H Abidi34, Heather Allewelt35, Amer Beitinjaneh36, Rachel Cook37, Robert F Cornell8, Joseph W Fay38, Gregory Hale39, Jennifer Holter Chakrabarty40, Sonata Jodele41, Kimberly A Kasow42, Anuj Mahindra43, Adriana K Malone44, Uday Popat45, J Douglas Rizzo5, Harry C Schouten46, Anne B Warwick47, William A Wood42, Mikkael A Sekeres2, Mark R Litzow48, Robert P Gale49, Shahrukh K Hashmi33. 1. Departments of Quantitative Health Sciences and Translational Hematology & Oncology Research, Cleveland Clinic Foundation, Cleveland, OH, United States. 2. Blood & Marrow Transplant Program, Cleveland Clinic, Cleveland, Ohio, United States. 3. CIBMTR (Center for International Blood and Marrow Transplant Research), Medical College of Wisconsin, Milwaukee, WI, United States. Electronic address: beshaw@mcw.edu. 4. CIBMTR (Center for International Blood and Marrow Transplant Research), Medical College of Wisconsin, Milwaukee, WI, United States; Division of Biostatistics, Medical College of Wisconsin, Milwaukee, WI, United States. 5. CIBMTR (Center for International Blood and Marrow Transplant Research), Medical College of Wisconsin, Milwaukee, WI, United States. 6. Departments of Quantitative Health Sciences and Translational Hematology & Oncology Research, Cleveland Clinic Foundation, Cleveland, OH, United States; Department of Medical Oncology, Academic Medical Center, Amsterdam, The Netherlands. 7. Hematology Branch, National Heart, Lung and Blood Institute, Bethesda, MD, United States. 8. Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States. 9. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States. 10. Pediatric Blood and Marrow Transplantation Program, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, United States. 11. Department of Hematology Oncology and Bone Marrow Transplantation, The Children's Mercy Hospitals and Clinics, Kansas City, MO, United States. 12. Stem Cell Transplantation and Cell Therapy, Rush University Medical Center, Chicago, IL, United States. 13. Royal Melbourne Hospital City Campus, Melbourne, Australia. 14. Division of Pediatrics Hematology, Children's Hospital of Orange County, Orange, CA, United States. 15. Department of Hematology, CHU Grenoble Alpes, Grenoble, France. 16. Tom Baker Cancer Center, Calgary, AB, Canada. 17. Blood and Marrow Transplant Program, Massachusetts General Hospital, Boston, MA, United States. 18. Blood and Marrow Transplantation, University of Kansas Medical Center, Kansas City, KS, United States. 19. Department of Pediatrics, Washington University School of Medicine in St. Louis, St. Louis, MO, United States. 20. Department of Medicine, University of Wisconsin Hospital and Clinics, Madison, WI, United States. 21. Division of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan. 22. Department of Hematology/Oncology, Mayo Clinic, Phoenix, AZ, United States. 23. Division of Hematology/Oncology, University of Virginia Health System, Charlottesville, VA, United States. 24. Bone Marrow Transplant Service, Division of Hematology, Memorial Sloan Kettering Cancer Center, New York, NY, United States. 25. Seidman Cancer Center, Case Western Reserve University, Cleveland, OH, United States. 26. Adult Bone Marrow Transplant, University Hospitals Bristol NHS Trust, Bristol, United Kingdom. 27. Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden; Centre for Clinical Research Sormland, Uppsala University, Uppsala, Sweden. 28. Department of Hematology & Oncology, National Cancer Research Center East, Chiba, Japan. 29. Department of Hematology-Oncology, Mount Sinai Hospital, New York, NY, United States. 30. Ohio State Medical Center, Columbus, OH, United States. 31. Division of Bone Marrow Transplant, Seattle Cancer Care Alliance, Seattle, WA, United States. 32. Department of Medicine, University of Maryland, Baltimore, MD, United States. 33. Department of Oncology, King Faisal Specialist Hospital, Riyadh, Saudi Arabia. 34. Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI, United States. 35. Duke University Medical Center, Durham, NC, United States. 36. University of Miami, Miami, FL, United States. 37. Oregon Health and Science University, Portland, OR, United States. 38. Baylor University Medical Center, Dallas, TX, United States. 39. Department of Hematology/Oncology, Johns Hopkins All Children's Hospital, St. Petersburg, FL, United States. 40. Department of Hematology/Oncology, University of Oklahoma, Oklahoma City, OK, United States. 41. Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States. 42. University of North Carolina at Chapel Hill, Chapel Hill, NC, United States. 43. Scripps Blood & Marrow Transplant Program, La Jolla, CA, United States. 44. Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY; United States. 45. MD Anderson Cancer Center, Houston, TX, United States. 46. Department of Hematology, Academische Ziekenhuis, Maastricht, Netherlands. 47. Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, MD, United States. 48. Dept. Of Medicine, Mayo Clinic, Rochester, MN, United States. 49. Department of Medicine, Imperial College London, London, United Kingdom.
Abstract
BACKGROUND: Exposures to DNA-damaging drugs and ionizing radiations increase risks of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). METHODS: 9028 recipients of hematopoietic cell autotransplants (1995-2010) for Hodgkin lymphoma (HL; n = 916), non-Hodgkin lymphoma (NHL; n = 3546) and plasma cell myeloma (PCM; n = 4566), reported to the CIBMTR, were analyzed for risk of subsequent AML or MDS. RESULTS: 335 MDS/AML cases were diagnosed posttransplant (3.7%). Variables associated with an increased risk for AML or MDS in multivariate analyses were: (1) conditioning with total body radiation versus chemotherapy alone for HL (HR = 4.0; 95% confidence interval [1.4, 11.6]) and NHL (HR = 2.5 [1.1, 2.5]); (2) ≥3 versus 1 line of chemotherapy for NHL (HR = 1.9 [1.3, 2.8]); and (3) subjects with NHL transplanted in 2005-2010 versus 1995-1999 (HR = 2.1 [1.5, 3.1]). Using Surveillance, Epidemiology and End Results (SEER) data, we found risks for AML/MDS in HL, NHL and PCM to be 5-10 times the background rate. In contrast, relative risks were 10-50 for AML and approximately 100 for MDS in the autotransplant cohort. CONCLUSIONS: There are substantial risks of AML and MDS after autotransplants for HL, NHL and PCM.
BACKGROUND: Exposures to DNA-damaging drugs and ionizing radiations increase risks of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). METHODS: 9028 recipients of hematopoietic cell autotransplants (1995-2010) for Hodgkin lymphoma (HL; n = 916), non-Hodgkin lymphoma (NHL; n = 3546) and plasma cell myeloma (PCM; n = 4566), reported to the CIBMTR, were analyzed for risk of subsequent AML or MDS. RESULTS: 335 MDS/AML cases were diagnosed posttransplant (3.7%). Variables associated with an increased risk for AML or MDS in multivariate analyses were: (1) conditioning with total body radiation versus chemotherapy alone for HL (HR = 4.0; 95% confidence interval [1.4, 11.6]) and NHL (HR = 2.5 [1.1, 2.5]); (2) ≥3 versus 1 line of chemotherapy for NHL (HR = 1.9 [1.3, 2.8]); and (3) subjects with NHL transplanted in 2005-2010 versus 1995-1999 (HR = 2.1 [1.5, 3.1]). Using Surveillance, Epidemiology and End Results (SEER) data, we found risks for AML/MDS in HL, NHL and PCM to be 5-10 times the background rate. In contrast, relative risks were 10-50 for AML and approximately 100 for MDS in the autotransplant cohort. CONCLUSIONS: There are substantial risks of AML and MDS after autotransplants for HL, NHL and PCM.
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