Blood Journal
Leading the way in experimental and clinical research in hematology

Better leukemia-free and overall survival in AML in first remission following cyclophosphamide in combination with busulfan compared to TBI

  1. Edward A. Copelan1,*,
  2. Betty K. Hamilton2,
  3. Belinda Avalos1,
  4. Kwang Woo Ahn3,
  5. Brian J. Bolwell2,
  6. Xiaochun Zhu3,
  7. Mahmoud Aljurf4,
  8. Koen van Besien5,
  9. Christopher N. Bredeson6,
  10. Jean-Yves Cahn7,
  11. Luciano J. Costa8,
  12. Marcos de Lima9,
  13. Robert Peter Gale10,
  14. Gregory A. Hale11,
  15. Joerg Halter12,
  16. Mehdi Hamadani13,
  17. Yoshihiro Inamoto14,
  18. Rammurti T. Kamble15,
  19. Mark R. Litzow16,
  20. Alison W. Loren17,
  21. David I. Marks18,
  22. Eduardo Olavarria19,
  23. Vivek Roy20,
  24. Mitchell Sabloff6,
  25. Bipin N. Savani21,
  26. Matthew Seftel22,
  27. Harry C. Schouten23,
  28. Celalettin Ustun24,
  29. Edmund K. Waller25,
  30. Daniel J. Weisdorf24,
  31. Baldeep Wirk26,
  32. Mary M. Horowitz3,
  33. Mukta Arora24,
  34. Jeff Szer27,
  35. Jorge Cortes28,
  36. Matt E. Kalaycio2,
  37. Richard T. Maziarz29, and
  38. Wael Saber30
  1. 1 Levine Cancer Institute, Carolinas Healthcare System, Charlotte, NC, United States;
  2. 2 Cleveland Clinic Foundation, Cleveland, OH, United States;
  3. 3 Center for International Blood and Marrow Transplant Research, Milwaukee, WI, United States;
  4. 4 King Faisal Specialist Hospital Center & Research, Riyadh, Saudi Arabia;
  5. 5 Weill Cornell Medical College, New York, NY, United States;
  6. 6 Division of Hematology, Department of Medicine, University of Ottawa and Ottawa Hospital Research Institute, Ottawa, ON, Canada;
  7. 7 Department of Hematology, University Hospital, Grenoble, France;
  8. 8 Medical University of South Carolina, Charleston, SC, United States;
  9. 9 University Hospitals Case Medical Center, Cleveland, OH, United States;
  10. 10 Section of Haematology, Division of Experimental Medicine, Department of Medicine, Imperial College, London, United Kingdom;
  11. 11 All Children's Hospital, St. Petersburg, FL, United States;
  12. 12 University Hospital Basel, Basel, Switzerland;
  13. 13 West Virginia University Hospitals, Inc., Morgantown, WV, United States;
  14. 14 Fred Hutchinson Cancer Research Center, Seattle, WA, United States;
  15. 15 Baylor College of Medicine Center for Cell and Gene Therapy, Houston, TX, United States;
  16. 16 Mayo Clinic, Rochester, MN, United States;
  17. 17 Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States;
  18. 18 Bristol Children's Hospital, Bristol, United Kingdom;
  19. 19 Catherine Lewis Center, Pamplona, Spain;
  20. 20 Mayo Clinic, Jacksonville, FL, United States;
  21. 21 Vanderbilt University Medical Center, Brentwood, TN, United States;
  22. 22 CancerCare Manitoba/University of Manitoba, Winnipeg, MB, Canada;
  23. 23 Academische Ziekenhuis Maastricht, Maastricht, Netherlands;
  24. 24 University of Minnesota Medical Center, Fairview, Minneapolis, MN, United States;
  25. 25 Emory University Hospital, Atlanta, GA, United States;
  26. 26 Shands HealthCare & University of Florida, Gainesville, FL, United States;
  27. 27 Royal Melbourne Hospital City Campus, VIC, Australia;
  28. 28 M.D. Anderson Cancer Center, Houston, TX, United States;
  29. 29 Oregon Health and Science University, Portland, OR, United States;
  30. 30 Center for International Blood and Marrow Transplant Research, MIlwaukee, WI, United States
  1. * Corresponding author; email: edward.copelan{at}

Key points

  • In combination with cyclophosphamide, intravenous busulfan is associated with better leukemia-free and overall survival in AML than TBI.


Cyclophosphamide combined with total body irradiation (Cy/TBI) or busulfan (BuCy) are the most widely used myeloablative conditioning regimens for allotransplants. Recent data regarding their comparative effectiveness is lacking. We analyzed data from the Center for International Blood and Marrow Transplant Research for 1230 subjects receiving a first hematopoietic cell transplant from a human-leukocyte antigen matched sibling or unrelated donor during years 2000-2006 for acute myeloid leukemia (AML) in first complete remission (CR) after conditioning with Cy/TBI or oral or intravenous (IV) BuCy. Multivariate analysis showed significantly less non-relapse mortality (relative risk [RR]=0.58; 95% confidence interval [CI]:0.39 – 0.86; P=0.007), and relapse after, but not before, 1 year post-transplant (RR=0.23; 95% CI: 0.08 – 0.65; P=0.006), and better leukemia-free survival (RR=0.70; 95% CI: 0.55 – 0.88; P=0.003) and survival (RR=0.68; 95% CI: 0.52 – 0.88; P=0.003) in persons receiving IV, but not oral, Bu compared to TBI. In combination with Cy, IV Bu is associated with superior outcomes compared to TBI in patients with AML in first CR.

  • Submitted July 18, 2013.
  • Accepted September 17, 2013.