Outcome of single fraction total body irradiation-conditioned stem cell transplantation in younger children with malignant disease--comparison with a busulphan-cyclophosphamide regimen.

The logistic difficulties of using fractionated total body irradiation (TBI) in the youngest children often limit the choice to single fraction TBI (sfTBI) or non-TBI-based regimens. We retrospectively evaluated 44 such children ( < 7 years) conditioned with either sfTBI (n = 26) or busulphan-cyclophosphamide (Bu-Cy) (n = 18), transplanted for hematological malignancies between 1988 and 2001. Both neutrophil and platelet engraftment were faster in the sfTBI group with a similar incidence of graft failure (6.8%). Acute GVHD (graft versus host disease) grade 2-4 occurred in 38.4% and 38.8% and chronic GVHD in 20% and 15.4% of the patients in the sfTBI and Bu-Cy groups, respectively Grade 2-4 GVHD was associated with reduced risk of relapse (p = 0.03). This finding was more pronounced in high-risk patients with 2/10 relapses in patients with GVHD grade 2-4, compared with 13/18 relapses among those with GVHD 0-1 (p = 0.05). The probability of overall survival was 43.3% in the sfTBI group and 33.3% in the Bu-Cy group (p = 0.6). However, the outcomes for high-risk patients and those with acute lymphoblastic leukemia were better in the sfTBI group. While hypothyroidism, growth hormone deficiency, learning problems and cataract formation were observed only in the sfTBI group, early cardiac toxicity, behavioral problems and seizures were more common in the Bu-Cy group. Thus, where fractionated TBI is not feasible, sfTBI offers improved survival in high-risk children with acute lymphoblastic leukemia compared with Bu-Cy, without an unacceptable increase in early or late toxicity.