Visceral Fat and Body Fat as Risk Factors for Methotrexate Toxicity in Pediatric Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma.

[BACKGROUND] Methotrexate (MTX) is essential for treating lymphoblastic leukemia, but high doses (5 g/m corporal surface) can cause significant gastrointestinal, renal, hepatic, and hematological toxicity. Body composition, particularly high body fat mass, can function as a third space and may increase toxicity by prolonging the drug's circulation time.

[AIM] To analyze the associations between body composition (body fat mass, visceral fat area, and skeletal muscle mass) and the incidence of MTX toxicity in patients with acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma.

[MATERIALS AND METHODS] A cohort of patients aged 6-18 years diagnosed with ALL and lymphoblastic lymphoma who received high-dose MTX without prior toxicity was included. Patients with preexisting renal failure or liver failure before MTX administration were excluded. Body composition was assessed using a multifrequency bioimpedance device.

[RESULTS] Regarding MTX toxicity, 30.2% of events occurred early, and this figure increased to 58.7% for late toxicity. Patients with a visceral fat area (VFA) ≥47 cm had a significantly higher risk of late toxicity (RR 2.8 (1.3-5.5), p = 0.01), as did those with high body fat mass (RR 2.0 (1.1-3.4), p = 0.01). For severe late toxicity, a VFA ≥47 cm was strongly correlated (RR 5.6 (1.3-22.6), p = 0.003), and high body fat mass remained a significant risk factor (RR 2.3 (1.03-5.5), p = 0.03). No significant associations were found with low phase angle, low skeletal muscle index, or overweight body mass index.

[CONCLUSION] A VFA ≥ 47 cm and a high percentage of body fat mass were associated with an increased risk of late MTX toxicity and severe late toxicity.