Body mass index does not influence pharmacokinetics or outcome of treatment in children with acute lymphoblastic leukemia

Author:

Hijiya Nobuko1,Panetta John C.1,Zhou Yinmei1,Kyzer Emily P.1,Howard Scott C.1,Jeha Sima1,Razzouk Bassem I.1,Ribeiro Raul C.1,Rubnitz Jeffrey E.1,Hudson Melissa M.1,Sandlund John T.1,Pui Ching-Hon1,Relling Mary V.1

Affiliation:

1. From the Departments of Oncology, Pharmaceutical Sciences, and Biostatistics, St Jude Children's Research Hospital, Memphis, TN; and the Departments of Pediatrics, Pharmaceutical Sciences, and Pharmacy and the Center for Pediatric Pharmacokinetics and Therapeutics, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN.

Abstract

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 ≤ 10th percentile; normal; at risk of overweight, BMI ≥ 85th and < 95th percentile; overweight, BMI ≥ 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.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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