Impact on survival and toxicity by duration of weight extremes during treatment for pediatric acute lymphoblastic leukemia: A report from the Children's Oncology Group

Abstract

Purpose: Previous studies regarding the influence of weight on event-free survival (EFS) and treatment-related toxicity (TRT) in childhood acute lymphoblastic leukemia (ALL) considered only weight at diagnosis. Inasmuch as weight varies substantially over treatment, we hypothesized its impact on EFS is instead determined by cumulative time spent at an extreme weight during therapy and on TRT by weight at the time of toxicity.

Patients and methods: In a cohort of 2,008 children treated for high-risk ALL in Children's Oncology Group study CCG-1961, we determined the effect on EFS of cumulative time receiving therapy at an extreme weight (either obese or underweight) between end of induction and start of maintenance therapy. We also evaluated the association between weight category and incidence and patterns of TRT during 13,946 treatment courses.

Results: Being obese or underweight at diagnosis and for ≥ 50% of the time between end of induction and start of maintenance therapy resulted in inferior EFS (hazard ratios, 1.43 and 2.30, respectively; global P < .001). Normalization of weight during that period resulted in mitigation of this risk comparable to never being obese or underweight. Obese or underweight status at start of each treatment course was significantly associated with specific patterns of TRT.

Conclusion: Influence of weight extremes on EFS and TRT is not set at diagnosis as previously reported but is moderated by subsequent weight status during intensive postinduction treatment phases. These observations suggest that weight is a potentially addressable risk factor to improve EFS and morbidity in pediatric ALL.

Fig 1.

CONSORT diagram. CCG, Children's Cancer Group; CDC, Centers for Disease Control and Prevention; ICU, intensive care unit; PAP, pokeweed antiviral protein. (*) One patient could not be unambiguously classified as either < 50% underweight or < 50% obese. Analyses that either excluded the patient or classified the patient into either category produced results that differed negligibly. Analysis excluding this patient is presented.

Fig 2.

Five-year event-free survival (EFS) by weight status at diagnosis and during therapy. Kaplan-Meier plots of EFS by (A) weight category at diagnosis (EFS as measured from diagnosis; n = 2,008) or (B) weight category over time during postinduction therapy (EFS as measured from beginning of maintenance; n = 1,581). Both plots demonstrate significantly worse EFS of patients in either weight extreme category as compared with normal/overweight patients.