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 < or = 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.
Baillargeon
Jacques
J
Center for Epidemiology and Biostatistics, University of Texas Health Science Center, San Antonio, 78229, USA. baillargeon@uthscsa.edu
Langevin
Anne-Marie
AM
Lewis
Margaret
M
Thomas
Paul J
PJ
Mullins
Judith
J
Dugan
John
J
Pollock
Brad H
BH
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001215:Asparaginase / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D016014:Linear Models; D008297:Male; D020714:Maximum Tolerated Dose; D009765:Obesity / Q000175:diagnosis; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000208:ethnology; D011336:Probability; D012074:Remission Induction; D018570:Risk Assessment; D012494:Sampling Studies; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index
D015415:Biomarkers; D001215:Asparaginase