Obesity Predicts Childhood Leukemia Relapse and Survival

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Preadolescents and teenagers with acute lymphoblastic leukemia who are overweight at diagnosis have a higher risk of leukemia relapse and poorer event-free survival.

Researchers from the Children’s Oncology Group analyzed data from 4356 patients diagnosed with acute lymphoblastic leukemia from 1988 to 1995 at age 2-20 years who were enrolled in five studies. Patients with Down’s syndrome and/or central nervous system disease at diagnosis were excluded. Obesity status, determined at diagnosis, was defined as a body mass index of more than 95th percentile per Centers for Disease Control and Prevention growth charts.

Anna Butturini, associate professor in clinical pediatrics, University of Southern California, and investigator for the Children’s Oncology Group, Arcadia, California, United States, presented the study’s results on December 3rd at the 46th Annual Meeting of the American Society of Hematology.

The results show that obesity at diagnosis did not affect outcome in patients who were younger than 10 years of age.

Among the 1026 patients who were 10 years or older, however, obesity status appeared to independently predict a 5-year risk of leukemia relapse and poorer rate of event-free survival. A multivariate analysis in these older patients showed that obesity increased the risk of leukemia relapse (hazard ratio-HR- 1.5, P =.013) and of unfavorable events (HR 1.5, P =.009).

Other independent predictors of poor outcome were a high white blood cell count at diagnosis and a slow rate of early response to induction therapy. Age had a borderline significance; sex, race, and type of therapy did not impact outcome.

To determine whether the negative effect on outcome in this age group was due to obesity status or due only to absolute body weight, the researchers analyzed the effect of weight in kilograms at diagnosis. Patients who were more than 60 kg had increased risk of leukemia relapse (HR 1.4, P =.002) and of unfavorable events (HR 1.4, P =.006). High white blood cell count at diagnosis and slow early response rate to induction therapy maintained their significance. Age, sex, race, and therapy did not impact outcome.

Independent analyses of obese patients who weighed less than 60 kg and non-obese patients who weighed more than 60 kg still led to the same results. Obesity and absolute weight of more than 60 kg at diagnosis were not associated with differences in early toxic deaths, response rates to initial phases of therapy, or days of hospitalization.

“The nature of our study and the characteristics of the database allow only speculations on the mechanisms of this effect,” said Dr. Butturini. “The finding that both obesity and weight affect outcome suggests that inadequate dosing and/or different pharmacokinetics in obese and heavier patients might be important.” Behavorial, endocrine, and metabolic differences might also have a role, she added.

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