Busulfan with 400 Centigray of Total Body Irradiation and Higher dose
Fludarabine. An alternative regimen for Hematopoietic Stem Cell
Transplantation in Pediatric Acute Lymphoblastic Leukemia.
Abstract
Background Hematopoietic stem cell transplantation can be
curative for children with difficult to treat leukemia. The conditioning
regimen utilised is known to influence outcomes. We report outcomes of
the conditioning regimen used at the Alberta Children’s Hospital,
consisting of busulfan (with pharmacokinetic target of 3750μmol*min/day
+/-10%) for 4 days, higher dose (250 mg/m2) fludarabine and 400
centigray of total body irradiation. Procedure This
retrospective study involved children receiving transplant for acute
lymphoblastic leukemia (ALL). It compared children who fell within the
target range for busulfan with those who were either not measured or
were measured and fell outside this range. All other treatment factors
were identical. Results Twenty-nine children (17 within target)
were evaluated. All subjects engrafted neutrophils with a median (IQR)
time of 14 days (8-30 days). The cumulative incidence of acute graft
versus host disease was 44.8% (95% CI 35.6 – 54.0%), while chronic
graft versus host disease was noted in 16.0% (95% CI 8.7% - 23.3%).
At two years, the overall survival was 78.1% (95% CI 70.8% - 86.4%)
and event free survival was 74.7% (95% CI 66.4% - 83.0%). Cumulative
incidence of relapse was 11.3% (95% CI 5.1% - 17.5%). There were no
statistically significant differences in between the group that received
targeted busulfan compared with the untargeted group.
Conclusion The current regimen used in children with ALL
results in outcomes comparable to standard treatment with acceptable
toxicities and significant reduction in radiation dose. Targeting
Busulfan dose in this cohort did not result in improved outcomes.