Association of BMI on outcomes in adolescent and young adult patients with ALL

CNS, central nervous system; PEG, pegylated.
*Adapted from Shimony, et al.^1
†Including pediatric protocols (00-001 and 05-001) and pediatric-inspired protocols (01-175 and 06-254).
^‡Asparaginase administration is marked in purple.

The standard measure of obesity was patient BMI at diagnosis, calculated based on Center for Disease Control (CDC) guidelines (Table 1).

Table 1. Measure of obesity*

BMI, body mass index *Data from Shimony, et al1 †The underweight and normal categories were unified for this analysis.
BMI categories	Patients aged 2–20 years, BMI per age-adjusted percentiles	Patients aged ≥20 years, BMI (kg/m2)
Underweight†	<5% percentile	<18.5 kg/m2
Normal†	5%–84.99% percentiles	18.5–24.99 kg/m2
Overweight	85%–94.99% percentiles	25–29.99 kg/m2
Obese	≥95% percentile	≥30 kg/m2

Results

A total of 388 patients with a median age of 24 years (range, 15–50 years) were included. More than half of patients were in the underweight (n = 10) or normal BMI range (n = 197) at diagnosis (normal BMI group, n = 207), and the remaining patients had a BMI of overweight (n = 97) or obese (n = 84; combined overweight/obese group, n = 181).

Toxicities

The toxicity analysis was based on 353 patients. The rate of any Grade 3/4 hepatotoxicity and any Grade 3/4 hyperglycemia was higher in patients with an overweight/obese vs those with a normal BMI. There was no significant difference in Grade 3/4 hypertriglyceridemia between BMI groups, as shown in Figure 2.

TG, hypertriglyceridemia.
*Adapted from Shimony, et al.¹

Response, survival, and relapse

Complete response

A total of 87% of patients achieved complete response with no difference between BMI groups (p = 0.84).

Overall survival

The 4-year overall survival (OS) was 74% and was higher in younger vs older AYA patients (79%; 95% confidence interval [CI], 73–84 vs 64%; 95% CI, 55–72; p = 0.003), and in patients with normal vs overweight/obese BMI (83%; 95% CI, 77–88 vs 64%; 95% CI, 56–71; p = 0.0001).

Separate analyses were conducted due to an association between the age group and BMI group. In the patients with normal BMI, there was a similar OS between younger vs older AYAs. In contrast, OS was higher in younger vs older AYAs who were overweight/obese (Figure 3).

BMI, body mass index; CI, confidence interval.
*Data from Shimony, et al.¹

Event-free survival

The 4-year event-free survival (EFS) was 70% and was higher in patients with a normal BMI vs those with an overweight/obese BMI (77%; 95% CI, 70–83 vs 63%; 95% CI, 55–70; p = 0.003).

The 4-year EFS rates were similar for younger and older AYAs with normal BMI. In contrast, the EFS rate was numerically higher in younger vs older AYAs who were overweight/obese; however, this was not statistically significant (Figure 4).

BMI, body mass index; CI, confidence interval.
*Data from Shimony, et al.¹

Relapse

The 4-year cumulative incidence of relapse (CIR) was 20.7% (95% CI, 15.9–25.9) and was not statistically different between BMI groups. Although 4-year CIR was similar in younger and older patients in the normal BMI group (17.9%; 95% CI, 10.6–26.9 vs 18.8%; 95% CI, 8.0–33.2; p = 0.89), the 4-year CIR was numerically lower in younger vs older patients in the overweight/obese group (17.1%; 95% CI, 9.0–27.5 vs 30.1%; 95% CI, 19.6–41.2; p = 0.13).

The 4-year cumulative incidence of non-relapse mortality was 7.3% (95% CI, 4.6–10.8) and was lower in patients with normal BMI vs those with overweight/obese BMI (2.8%; 95% CI, 0.9–6.7; vs 11.7%; 95% CI, 6.9–17.8; p = 0.006). The cumulative incidence of non-relapse mortality was similar between younger and older patients in each BMI group.

Multivariable analysis

• In the multivariable analysis, the following variables were significantly associated with worse OS:
  • BMI (overweight/obese vs normal; hazard ratio [HR], 2.38; 95% CI, 1.56–3.63; p < 0.0001)
  • White blood cell count (≥30,000 × 10⁹/L vs <30,000 × 10⁹/L; HR, 1.79; 95% CI, 1.20–2.69; p = 0.005)
  • Immunophenotype (B vs T; HR, 2.27; 95% CI, 1.26–4.09; p = 0.006)
• Hypertriglyceridemia was significantly associated with improved OS (HR, 0.33; 95% CI, 0.18–0.61; p < 0.0001).
• Allogeneic hematopoietic stem cell transplantation was significantly associated with worse OS in the univariate analysis (HR, 2.04; 95 CI, 1.26–3.30; p = 0.004) but not in the multivariable analysis (HR, 1.31; 95% CI, 0.80–2.14; p = 0.28).
• Age was significantly associated with worse OS in the univariate analysis (HR, 1.03; 95% CI, 1.01–1.05; p = 0.003) but not in the multivariable analysis.
• There was a trend toward worse OS with Grade 3/4 hyperglycemia (HR, 1.51; 95% CI, 0.99–2.28; p = 0.054).

Conclusion

In this study of AYA patients treated on a pediatric regimen, being overweight or obese was associated with higher non-relapse mortality, worse EFS, and worse OS. In particular, a higher BMI was associated with high relapse rates and poor survival among the older AYAs (aged >30 years). The study also demonstrated that hypertriglyceridemia was associated with improved survival and decreased risk of relapse. These results warrant further research on the impact of BMI on treatment toxicities and outcomes among patients of all ages with ALL.