New research suggests several factors may be associated with the risk of short stature and excess weight gain in children with acute lymphoblastic leukemia (ALL).
Researchers found that patients who were younger at ALL diagnosis had an increased risk of becoming overweight or obese both during and after therapy.
Patients had an increased risk of short stature after therapy if they were older at diagnosis or had standard or high-risk disease, higher white blood cell counts at diagnosis, and central nervous system disease.
The researchers reported these findings in Cancer.
The team looked at 372 children with ALL, reviewing changes in their body mass index (BMI), weight, and height from diagnosis to 5 years after treatment ended.
The patients were treated with the Total XV protocol between 2000 and 2007 (NCT00137111). They received 6 weeks of induction therapy, 8 weeks of consolidation, and continuation for 120 weeks in females and 146 weeks in males.
Roughly a quarter of patients were overweight or obese at diagnosis, but that increased to roughly half of patients by the time they had been off therapy for 5 years.
“Over the whole population that was studied, we found statistically significant weight gain even during remission-induction therapy,” said study author Hiroto Inaba, MD, PhD, of St. Jude Children’s Research Hospital in Memphis, Tennessee.
Patients’ median BMI z scores increased significantly during induction (P<0.001) and reinduction (P=0.001) with glucocorticoid therapy as well as in the first year after therapy ended (P=0.006).
At various points during treatment, there were significant differences in BMI z scores according to sex, race, and disease risk group. However, these differences were not present after therapy.
On the other hand, there were significant differences in BMI z scores according to age both during and after therapy.
Between week 21 of treatment and 3 years after therapy ended, patients who were ages 2 to 9 at diagnosis had median BMI z scores that were significantly higher than scores of patients who were age 10 or older at diagnosis (P≤0.033 for all time points).
The researchers also found that patients who were of a healthy weight or underweight at the time of diagnosis had a significantly higher risk of becoming overweight or obese during or after therapy if they were ages 2 to 9 at diagnosis, compared to the older patients (P=0.001).
The researchers found that height z scores declined during treatment and improved after it ended, although z scores “never improved to the levels noted at the time of diagnosis.”
Median height z scores at the end of induction and in continuation weeks 1 to 21 were significantly higher in patients age 10 or older at diagnosis than in patients ages to 2 to 9 at diagnosis (P≤0.038 for all time points).
However, the median height z scores at 5 years off therapy were significantly higher for the younger patients than for the older patients (P=0.011).
The median height z scores were higher for patients with low-risk disease than for standard- or high-risk patients in weeks 17, 21, 48, and 146 of treatment and at 1 to 3 years after therapy ended (P≤0.024 for all time points).
At 3 years to 5 years after treatment ended, the median height z scores were significantly higher among patients with white blood cell counts below 50 × 109/L at diagnosis (P≤0.018 for all time points).
Patients without central nervous system disease had significantly higher median height z scores at 3 years after treatment ended (P=0.029).
Males had significantly higher median height z scores than females in weeks 96 and 120 of therapy (P≤0.009 for both time points).
And white patients had higher median height z scores than black patients at 2 to 4 years after treatment ended (P≤0.027 for all time points).
To address the issue of excess weight gain in ALL patients, the researchers suggested early interventions, such as education about proper diet and exercise.
“When you look at the literature of childhood obesity prevention for the general population, there are interventions that could also help ALL patients,” said study author Emily Browne, of St. Jude.
“But we need to adapt those recommendations to take the cancer therapy into account.”
For the issue of height, the researchers recommended evaluating certain patients for growth hormone deficiency.
The team also noted that further study is needed to determine whether emerging therapeutic approaches can reduce toxicities without compromising antileukemic effects.
“We are hoping new therapeutic options can decrease intensity of chemotherapy and keep normal tissues intact,” Dr. Inaba said. “But until then, we’re collaborating with multiple clinical departments to help ensure a good, quality cure and a good quality of life in survivorship.”
This research was supported by grants from the National Institutes of Health and ALSAC, the fundraising and awareness organization of St. Jude.