Body mass index does not influence pharmacokinetics or outcome of treatment in children with acute lymphoblastic leukemia.
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.
Hijiya
Nobuko
N
Department of Oncology, St Jude Children's Research Hospital, 332 North Lauderdale St, Memphis, TN 38105-2794, USA. nobuko.hijiya@stjude.org
Panetta
John C
JC
Zhou
Yinmei
Y
Kyzer
Emily P
EP
Howard
Scott C
SC
Jeha
Sima
S
Razzouk
Bassem I
BI
Ribeiro
Raul C
RC
Rubnitz
Jeffrey E
JE
Hudson
Melissa M
MM
Sandlund
John T
JT
Pui
Ching-Hon
CH
Relling
Mary V
MV
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
D003561:Cytarabine; D013713:Teniposide; D015122:Mercaptopurine; D008727:Methotrexate