Treatment failure and associated factors in pediatric Hodgkin lymphoma: a decade of institutional experience from a middle-income country

Despite excellent overall outcomes in pediatric Hodgkin lymphoma (HL), a subset of patients experiences relapse or primary refractory disease, necessitating intensive salvage therapy and exposing them to additional treatment-related toxicity. Data regarding treatment failure and its predictors from low- and middle-income countries remain limited. This study aimed to evaluate treatment outcomes and identify factors associated with relapse and refractory disease in pediatric HL patients treated at a tertiary referral center over a 10-year period. This retrospective cohort study included 83 pediatric patients diagnosed with HL between 2014 and 2024 at a tertiary referral center in Iran, reflecting real-world treatment experience in a middle-income setting, who had baseline PET/CT staging and complete outcome data available; three additional patients who lacked baseline PET/CT staging were excluded to ensure uniform staging methodology. Demographic, clinical, histopathological, laboratory, treatment, and outcome data were collected from medical records. Treatment failure was defined as relapse following complete remission or primary refractory disease. Associations between baseline characteristics and treatment failure were evaluated using univariate analyses. The cohort comprised 54 males (65.1%) and 29 females (34.9%), with a mean age at diagnosis of 10.72 ± 3.86 years. Stage III disease was the predominant presentation (66.3%). Continuous complete remission was achieved in 58 patients (69.8%), while 24 patients (30.2%) experienced treatment failure, including 14 relapses (16.9%) and 11 cases of primary refractory disease (13.3%), with 1 patient classified as both relapsed and refractory. Younger age at diagnosis was significantly associated with relapse (8.29 ± 3.73 vs. 11.22 ± 3.72 years, p = 0.015). Elevated erythrocyte sedimentation rate (ESR > 50 mm/hr) was also associated with relapse (42.9% vs. 11.6%, p = 0.010). Fever (45.5% vs. 8.3%, p = 0.005) and night sweats (36.4% vs. 8.3%, p = 0.024) at diagnosis were significantly associated with primary refractory disease. Histological subtype (classical HL vs. NLPHL), disease stage, and first-line chemotherapy regimen were not significantly associated with treatment failure. Among patients with treatment failure, ESHAP was the most frequently administered salvage regimen, and 14 patients (16.9%) received brentuximab vedotin or nivolumab. Treatment failure occurred in nearly one-third of pediatric HL patients in this cohort. Younger age and elevated ESR were associated with relapse, whereas fever and night sweats predicted primary refractory disease. These findings may aid risk stratification and support the need for larger prospective studies to optimize treatment strategies and improve outcomes in pediatric HL.