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

Nobuko Hijiya, John C. Panetta, Yinmei Zhou, Emily P. Kyzer, Scott Howard, Sima Jeha, Bassem I. Razzouk, Raul C. Ribeiro, Jeffrey E. Rubnitz, Melissa M. Hudson, John T. Sandlund, Ching Hon Pui, Mary V. Relling

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)3997-4002
Number of pages6
JournalBlood
Volume108
Issue number13
DOIs
StatePublished - Dec 15 2006

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Pharmacokinetics
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Toxicity
Body Mass Index
Chemotherapy
Drug Therapy
Thinness
Population

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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Body mass index does not influence pharmacokinetics or outcome of treatment in children with acute lymphoblastic leukemia. / Hijiya, Nobuko; Panetta, John C.; Zhou, Yinmei; Kyzer, Emily P.; Howard, Scott; Jeha, Sima; Razzouk, Bassem I.; Ribeiro, Raul C.; Rubnitz, Jeffrey E.; Hudson, Melissa M.; Sandlund, John T.; Pui, Ching Hon; Relling, Mary V.

In: Blood, Vol. 108, No. 13, 15.12.2006, p. 3997-4002.

Research output: Contribution to journalArticle

Hijiya, N, Panetta, JC, Zhou, Y, Kyzer, EP, Howard, S, Jeha, S, Razzouk, BI, Ribeiro, RC, Rubnitz, JE, Hudson, MM, Sandlund, JT, Pui, CH & Relling, MV 2006, 'Body mass index does not influence pharmacokinetics or outcome of treatment in children with acute lymphoblastic leukemia', Blood, vol. 108, no. 13, pp. 3997-4002. https://doi.org/10.1182/blood-2006-05-024414
Hijiya, Nobuko ; Panetta, John C. ; Zhou, Yinmei ; Kyzer, Emily P. ; Howard, Scott ; Jeha, Sima ; Razzouk, Bassem I. ; Ribeiro, Raul C. ; Rubnitz, Jeffrey E. ; Hudson, Melissa M. ; Sandlund, John T. ; Pui, Ching Hon ; Relling, Mary V. / Body mass index does not influence pharmacokinetics or outcome of treatment in children with acute lymphoblastic leukemia. In: Blood. 2006 ; Vol. 108, No. 13. pp. 3997-4002.
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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.",
author = "Nobuko Hijiya and Panetta, {John C.} and Yinmei Zhou and Kyzer, {Emily P.} and Scott Howard and Sima Jeha and Razzouk, {Bassem I.} and Ribeiro, {Raul C.} and Rubnitz, {Jeffrey E.} and Hudson, {Melissa M.} and Sandlund, {John T.} and Pui, {Ching Hon} and Relling, {Mary V.}",
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AU - Hijiya, Nobuko

AU - Panetta, John C.

AU - Zhou, Yinmei

AU - Kyzer, Emily P.

AU - Howard, Scott

AU - Jeha, Sima

AU - Razzouk, Bassem I.

AU - Ribeiro, Raul C.

AU - Rubnitz, Jeffrey E.

AU - Hudson, Melissa M.

AU - Sandlund, John T.

AU - Pui, Ching Hon

AU - Relling, Mary V.

PY - 2006/12/15

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N2 - 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.

AB - 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.

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