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Obesity and Outcome in Pediatric Acute Lymphoblastic Leukemia

Anna M. Butturini, Frederick J. Dorey, Beverly J. Lange, David W. Henry, Paul S. Gaynon, Cecilia Fu, Janet Franklin, Stuart E. Siegel, Nita L. Seibel, Paul C. Rogers, Harland Sather, Michael Trigg, W. Archie Bleyer, William L. Carroll

From the Childrens Hospital Los Angeles and Keck School of Medicine, University of Southern California, Los Angeles; Children's Oncology Group Statistical Center, Arcadia, CA; Children's Hospital of Philadelphia, Philadelphia, PA; Pharmacy Practice, University of Kansas Medical Center, Kansas City, KS; Children's National Medical Center, Washington, DC; Paediatric Oncology/Haematology/Bone Marrow Transplantation, British Columbia Children's Hospital and University of British Columbia, Vancouver, British Columbia, Canada; Medical and Scientific Affairs, Merck, North Wales, PA; Doernbecher Children's Hospital, Oregon Health and Science University, Bend, OR; and the New York University Medical Center, New York, NY

Address reprint requests to Anna M. Butturini, MD, Division of Hematology Oncology, Childrens Hospital Los Angeles, 4650 Sunset Blvd, Los Angeles, CA 90027; e-mail: abutturini{at}chla.usc.edu

Purpose: To evaluate the effect of obesity (defined as a body mass index > 95th percentile for age and sex at diagnosis) on outcome of pediatric acute lymphoblastic leukemia (ALL).

Patients and Methods: We retrospectively analyzed data from 4,260 patients with newly diagnosed ALL enrolled from 1988 to 1995 onto five concurrent Children's Cancer Group studies. Results were verified in a second cohort of 1,733 patients enrolled onto a sixth study from 1996 to 2002.

Results: The 1988 to 1995 cohort included 343 obese and 3,971 nonobese patients. The 5-year event-free survival rate and risk of relapse in obese versus nonobese patients were 72% ± 2.4% v 77% ± 0.6% (P = .02) and 26 ± 2.4 v 20 ± 0.6 (P = .02), respectively. After adjusting for other prognostic variables, obesity's hazard ratios (HRs) of events and relapses were 1.36 (95% CI, 1.04 to 1.77; P = .021) and 1.29 (95% CI, 1.02 to 1.56; P = .04), respectively. The effect of obesity was prominent in the 1,003 patients 10 years old at diagnosis; in this subset, obesity's adjusted HRs of events and relapses were 1.5 (95% CI, 1.1 to 2.1; P = .009) and 1.5 (95% CI, 1.2 to 2.1; P = .013), respectively. In a second cohort of 1,160 patients 10 years old, obesity's adjusted HRs of events and relapses were 1.42 (95% CI, 1.03 to 1.96; P = .032) and 1.65 (95% CI, 1.13 to 2.41; P = .009), respectively. The effect of obesity on outcome was unrelated to changes in chemotherapy doses, length of intervals between chemotherapy cycles, or incidence and severity of therapy-related toxicity.

Conclusion: Obesity at diagnosis independently predicts likelihood of relapse and cure in preteenagers and adolescents with ALL.

The Children's Cancer Group studies that originated the databases analyzed in this article were supported by Grants No. CA98543 and CA13539.

Presented in part in abstract format at the 46th Annual Meeting of the American Society of Hematology, December 4-7, 2004, San Diego, CA; and the 20th Annual Meeting of the International Society of Pediatric Oncology, April 15-17, 2005, Los Angeles, CA.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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