title: Comparison of preparative regimens in transplants for children with acute lymphoblastic leukemia.
abstract: OBJECTIVE
  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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: International Bone Marrow Transplant Registry, Health Policy Institute, and Division of Pediatric Hematology/Oncology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Davies
authors.forename: N K
authors.initials: NK
authors.lastname: Ramsay
authors.forename: J P
authors.initials: JP
authors.lastname: Klein
authors.forename: D J
authors.initials: DJ
authors.lastname: Weisdorf
authors.forename: B
authors.initials: B
authors.lastname: Bolwell
authors.forename: J Y
authors.initials: JY
authors.lastname: Cahn
authors.forename: B M
authors.initials: BM
authors.lastname: Camitta
authors.forename: R P
authors.initials: RP
authors.lastname: Gale
authors.forename: S
authors.initials: S
authors.lastname: Giralt
authors.forename: C
authors.initials: C
authors.lastname: Heilmann
authors.forename: P J
authors.initials: PJ
authors.lastname: Henslee-Downey
authors.forename: R H
authors.initials: RH
authors.lastname: Herzig
authors.forename: R
authors.initials: R
authors.lastname: Hutchinson
authors.forename: A
authors.initials: A
authors.lastname: Keating
authors.forename: H M
authors.initials: HM
authors.lastname: Lazarus
authors.forename: G A
authors.initials: GA
authors.lastname: Milone
authors.forename: S
authors.initials: S
authors.lastname: Neudorf
authors.forename: W S
authors.initials: WS
authors.lastname: Perez
authors.forename: R L
authors.initials: RL
authors.lastname: Powles
authors.forename: H G
authors.initials: HG
authors.lastname: Prentice
authors.forename: G
authors.initials: G
authors.lastname: Schiller
authors.forename: G
authors.initials: G
authors.lastname: Socié
authors.forename: M
authors.initials: M
authors.lastname: Vowels
authors.forename: J
authors.initials: J
authors.lastname: Wiley
authors.forename: A
authors.initials: A
authors.lastname: Yeager
authors.forename: M M
authors.initials: MM
authors.lastname: Horowitz
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation; D002066:Busulfan / Q000008:administration & dosage; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000628:therapy*; D012008:Recurrence; D012189:Retrospective Studies; D018570:Risk Assessment; D016019:Survival Analysis; D014916:Whole-Body Irradiation
chemical_list: D003520:Cyclophosphamide; D002066:Busulfan