Obesity or underweight status at diagnosis has influence on outcome in pediatric acute lymphoblastic leukemia (ALL) patients, but a new study shows that the risk can be mitigated if weight status changes following treatment induction. Previous work had only assessed the association between weight at diagnosis and outcome.
“Intensification of therapy for childhood ALL has achieved 5-year survival approaching 90%,” wrote researchers led by Etan Orgel, MD, of Miller Children’s Hospital in Long Beach, California. “However, subsets of patients remain at greater risk for both treatment-related toxicity (TRT) and poorer event-free survival (EFS) from combinations of factors relating to host, disease, and treatment.”
The new study examined the influence of weight in a cohort of 2,008 patients in the Children’s Oncology Group study CCG-1961; they included weight at diagnosis as well as associations between weight and incidence of toxicity during 13,946 treatment courses. The results were published in the May 1 issue of the Journal of Clinical Oncology.
Of the total cohort, 279 patients (14%) were obese at diagnosis, and 117 (6%) were underweight. The 5-year EFS rate for patients who were obese at diagnosis was 64%; the rate was 65% for underweight patients, compared with 74% for normal or overweight (but not obese) patients (P = .002).
The analysis also included 1,581 patients who were alive and disease-free when maintenance began. In this group, those who spent at least 50% of the time either obese or underweight had poorer EFS than those who spent less than 50%, or no time at all, in those weight categories.
The greatest risk was seen in patients who presented at diagnosis as obese or underweight, and then remained in that category for at least 50% of the maintenance phase as well. Interestingly, those children who were obese or underweight at diagnosis but then normalized their weight for more than half of the pre-maintenance therapy had a similar risk profile to those patients who were never obese or underweight. There was also a protective effect seen (HR = 0.52; 95% CI, 0.32-0.83) for patients who started in the normal weight category, and then spent less than half the pre-maintenance period underweight.
In the full cohort, the researchers found a significant association between weight category and the risk of grade 3 or 4 treatment toxicity (P = .008). Hepatic and pancreatic toxicities were more common among the obese patients, while pulmonary toxicity and fungal infections were more common among underweight patients.
“This study identifies a subset of patients who do not seem to be fully benefiting from therapeutic advances in pediatric ALL,” the investigators wrote. “Our results contrast sharply with those of previous studies in ALL by shifting the focus on weight beyond the period of diagnosis to accurately reflect the experience of patients as they progress through therapy.” This suggests that nutritional interventions could improve both toxicity and response to treatment in the future.