L-asparaginase as a marker of chemotherapy dose modification in children with acute lymphoblastic leukemia

BACKGROUND. The objective of the current study was to compare chemotherapy dose modifications in obese (a body mass index [BMI] > 95%) and nonobese (a BMI ≤ 95%) pediatric patients with acute lymphoblastic leukemia (ALL). METHODS. The study cohort was comprised of 199 pediatric patients diagnosed with ALL who were treated at 1 of 2 South Texas pediatric oncology centers between 1990-2000. The relative chemotherapy dose modification during the induction phase of chemotherapy was calculated as the ratio of 1) the actual administered dose of L-asparaginase and 2) the protocol-calculated dose of L-asparaginase. The extent to which the chemotherapy dose modification varied according to obesity status was assessed using stratified Student t tests and an ordinary least-squares regression analysis. RESULTS. Obese ALL patients were found to exhibit a 7% decrease in the mean relative modification of L-asparaginase during induction chemotherapy compared with their nonobese counterparts. This finding was statistically significant (P = 0.009), even after adjustment for gender, age, ethnicity, and clinical institution. CONCLUSIONS. To the authors' knowledge, the current study is the first published report of an obesity-associated chemotherapy dose modification in pediatric patients with ALL, the most common childhood malignancy. It will be important to examine whether these findings are consistent with those observed in future studies, and ultimately to assess the association between obesity-related dose modifications and long-term cancer outcomes.