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Comparison of Preparative Regimens in Transplants for Children With Acute Lymphoblastic Leukemia

From the International Bone Marrow Transplant Registry, Health Policy Institute, and Division of Pediatric Hematology/Oncology, Medical College of Wisconsin, Milwaukee, WI; University of California–Los Angeles, CA; University of Minnesota, Minneapolis, MN; Cleveland Clinic Foundation, and University Hospitals of Cleveland, Ireland Cancer Center, Cleveland, OH; Centre Hospitalier Universitaire Bescancon, Besancon, and Hôpital Saint-Louis, Paris, France; M.D. Anderson Cancer Center, University of Texas, Houston, TX; Righospitalet, Copenhagen University Hospital, Copenhagen, Denmark; University of South Carolina, Columbia, SC; Brown Cancer Center, Louisville, KY; University of Michigan Medical Center, Ann Arbor, MI; University of Toronto, Toronto, Ontario, Canada; Fundaleu, Buenos Aires, Argentina; University of Pittsburgh, Pittsburgh, PA; The Royal Marsden NHS Trust, Surrey, United Kingdom; Royal Free Hospital, London, United Kingdom; Sydney Children’s Hospital, Randwick, New South Wales, Australia; University of North Carolina–Chapel Hill, Chapel Hill, NC; and Emory University School of Medicine, Atlanta, GA.

Address reprint requests to Mary M. Horowitz, MD, MS, International Bone Marrow Transplant Registry, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226; email marymh{at}mcw.edu

PURPOSE: Preparative regimens involving total-body irradiation (TBI) produce significant late toxicities in some children who receive bone marrow transplants, including impaired growth and intellectual development. Busulfan is often used as an alternative to TBI, but there are few data regarding its relative efficacy.

PATIENTS AND METHODS: We compared outcomes of HLA-identical sibling transplants for acute lymphoblastic leukemia (ALL) in children (< 20 years of age) who received cyclophosphamide plus TBI (CY/TBI) (n = 451) versus those who received busulfan plus cyclophosphamide (Bu/CY) (n = 176) for pretransplant conditioning. Patients received transplants between 1988 and 1995 and their results were reported to the International Bone Marrow Transplant Registry by 144 participating institutions. The CY/TBI and Bu/CY groups did not differ in gender, immune phenotype, leukocyte count at the time of diagnosis, chromosome abnormalities, remission status, or length of initial remission. T-cell depletion was used more frequently in the CY/TBI group; the Bu/CY group included a higher proportion of children who were less than 5 years of age. The median follow-up period was 37 months.

RESULTS: The 3-year probabilities of survival were 55% (95% confidence interval [CI], 50% to 60%) with TBI/CY and 40% (95% CI, 32% to 48%) with Bu/CY (univariate P = .003). The 3-year probabilities of leukemia-free survival were 50% (95% CI, 45% to 55%) and 35% (95% CI, 28% to 43%), respectively (univariate P = .005). In a multivariate analysis, the risks of relapse were similar in the two groups (relative risk [RR], 1.30 for Bu/CY v CY/TBI; P = .1). Treatment-related mortality was higher in the Bu/CY group (RR, 1.68; P = .012). Death and treatment failure (relapse or death, inverse of leukemia-free survival) were more frequent in the Bu/CY group (RR, 1.39; P = .017 for death; RR, 1.42; P = .006 for treatment failure).

CONCLUSION: These data indicate superior survival with CY/TBI conditioning, compared with Bu/CY conditioning, for HLA-identical sibling bone marrow transplants in children with ALL.

All support information is given in the Appendix.

The contents of this article are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute.

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