title: Body mass index does not influence pharmacokinetics or outcome of treatment in children with acute lymphoblastic leukemia.
abstract: There is conflicting information about the influence of body mass index (BMI) on the pharmacokinetics, toxicity, and outcome of chemotherapy. We compared pharmacokinetics, outcome, and toxicity data across 4 BMI groups (underweight, BMI < or = 10th percentile; normal; at risk of overweight, BMI > or = 85th and < 95th percentile; overweight, BMI > or = 95th percentile) in 621 children with acute lymphoblastic leukemia (ALL) treated on 4 consecutive St Jude Total Therapy studies. Chemotherapy doses were not adjusted to ideal BMI. Estimates of overall survival (86.1% +/- 3.4%, 86.0% +/- 1.7%, 85.9% +/- 4.3%, and 78.2% +/- 5.5%, respectively; P = .533), event-free survival (76.2% +/- 4.2%, 78.7% +/- 2.1%, 73.4% +/- 5.5%, and 72.7% +/- 5.9%, respectively; P = .722), and cumulative incidence of relapse (16.0% +/- 3.7%, 14.4% +/- 1.8%, 20.6% +/- 5.1%, and 16.7% +/- 5.1%, respectively; P = .862) did not differ across the 4 groups. In addition, the intracellular levels of thioguanine nucleotides and methotrexate polyglutamates did not differ between the 4 BMI groups (P = .73 and P = .74, respectively). The 4 groups also did not differ in the overall incidence of grade 3 or 4 toxicity during the induction or postinduction periods. Further, the systemic clearance of methotrexate, teniposide, etoposide, and cytarabine did not differ with BMI (P > .3). We conclude that BMI does not affect the outcome or toxicity of chemotherapy in this patient population with ALL.
authors.affiliation: Department of Oncology, St Jude Children's Research Hospital, 332 North Lauderdale St, Memphis, TN 38105-2794, USA. nobuko.hijiya@stjude.org
authors.forename: Nobuko
authors.initials: N
authors.lastname: Hijiya
authors.forename: John C
authors.initials: JC
authors.lastname: Panetta
authors.forename: Yinmei
authors.initials: Y
authors.lastname: Zhou
authors.forename: Emily P
authors.initials: EP
authors.lastname: Kyzer
authors.forename: Scott C
authors.initials: SC
authors.lastname: Howard
authors.forename: Sima
authors.initials: S
authors.lastname: Jeha
authors.forename: Bassem I
authors.initials: BI
authors.lastname: Razzouk
authors.forename: Raul C
authors.initials: RC
authors.lastname: Ribeiro
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Rubnitz
authors.forename: Melissa M
authors.initials: MM
authors.lastname: Hudson
authors.forename: John T
authors.initials: JT
authors.lastname: Sandlund
authors.forename: Ching-Hon
authors.initials: CH
authors.lastname: Pui
authors.forename: Mary V
authors.initials: MV
authors.lastname: Relling
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D015992:Body Mass Index; D002648:Child; D002675:Child, Preschool; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D015122:Mercaptopurine / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000401:mortality; D011237:Predictive Value of Tests; D012074:Remission Induction; D012189:Retrospective Studies; D013713:Teniposide / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics
chemical_list: D003561:Cytarabine; D013713:Teniposide; D015122:Mercaptopurine; D008727:Methotrexate