HL-300: Long-Term Toxicity of ABVD in Paediatric Hodgkin Lymphoma: A Prospective Longitudinal Cohort Study

Abstract

Context ABVD is a standard therapy in adult Hodgkin lymphoma (HL); in children, ABVD is not the standard of care due to concerns regarding long-term toxicities. However, no studies have evaluated long-term toxicities of ABVD in this population. Objective To study long-term toxicities of ABVD in paediatric HL survivors. Setting and Design One hundred fifty-seven paediatric HL survivors (<18 years age, free from relapse >2 years) treated with ABVD at a tertiary care centre between January 2003–December 2013 were clinically evaluated at each follow-up visit, single time assessment by MUGA scan, spirometry with DLCO, and TSH and total T4 measurement. Binary logistic regression analysis was used to identify risk factors for long-term toxicities and ordinal logistic regression analysis to study predictors for multiple late adverse effects. Patients Median age: 10 years (3–18); 88%: males, 54%: advanced HL, and 50%: B symptoms. Median of four chemotherapy cycles delivered (1–8), and the median doxorubicin and bleomycin doses were 300 mg/m2 (range 150–400) and 80 IU/m2 (range 50–160), respectively. One hundred ten patients received radiation: 93 (59.2%) neck and 12 (7.6%) mediastinal. Median follow-up at time of toxicity evaluation was 67 months with 56% and 36% patients having completed 10 and 12 year of clinical follow-up, respectively. Results No secondary malignancies or symptomatic cardiac or pulmonary toxicity were seen. Twenty-eight patients (18.1%) had asymptomatic LVEF reduction (<55%), which was associated with mediastinal radiation (OR 3.57 95% CI 0.99–12.5, p=0.05). In addition, 41.7% had abnormal DLCO, and 43.7% had abnormal spirometry, which corelated with age >10 years (OR 4.2 95% CI 1.81–9.73, p=0.001) and male sex (OR 4.16 95% CI 1.09–16.66, p=0.03). Development of subclinical (44.8%) and overt (12.7%) hypothyroidism was related to neck RT (OR 35.1, 95% CI 13.8–89.3, p <0.01). Age >10 years and neck radiation predicted for development of multiple late effects. Number of chemotherapy cycles or dose of doxorubicin/bleomycin did not correlate with development of any toxicity. Conclusions ABVD remains safe in children <10 years of age with no correlation to development of late toxicities. Thyroid dysfunction and asymptomatic cardiac dysfunction seem to be sequelae of radiation. Children >10 years of age are more susceptible to multiple late effects and should be followed up closely.