Radiation-induced Lymphopenia in Pediatric Medulloblastoma

Introduction: The impact of radiotherapy-induced lymphopenia on pediatric medulloblastoma outcomes remains debated, with some evidence suggesting a potential risk of tumor recurrence. This theory has not been explored in low-middle-income countries where other factors may have a greater influence on prognosis. Methods: We retrospectively reviewed the medical charts of all children 3 to 18 years of age, diagnosed with medulloblastoma at KHCC/Jordan between 2017 and 2023 and treated with upfront craniospinal irradiation (CSI). We reviewed their clinical and tumor characteristics, lymphocytes’ count during and after radiotherapy, and outcome. We considered grade-3 lymphopenia (<0.2 to 0.5×10 9 /L) as the cutoff number for survival analysis. Results: Sixty-six patients were identified (59% male). The median age at diagnosis was 9 years (range: 4.8 to 17.9 y). Thirty-eight tumors (58%) were subgrouped; most (n=15, 39%) were subgroup-4. Thirty-five patients (53%) with completely resected nonmetastatic tumors received 23.4 Gy CSI with tumor bed boost. Twenty-nine patients (44%) received radiotherapy within 49 days from their tumor resection, and 91% finished radiotherapy within 51 days. Forty-one patients (62%) received dexamethasone during radiotherapy. Most patients (n=63, 96%) received vincristine during radiotherapy, and 3 received, in addition, carboplatin or etoposide. More than 50% of patients had grade ≥3 lymphopenia starting from week 2 of radiotherapy and continued until week 6; however, this dropped to 6.1% at weeks 4 to 6 postradiation. With a median follow-up of 3.5 years (range: 0.9 to 7.6 y), the 3-year RFS and OS were 75% and 86%, respectively. Gender, molecular subgroup, and lymphopenia grade ≥3 at weeks 4, 5, or 4 to 6 weeks after radiotherapy, were not prognostic for PFS. Metastatic disease was associated with a nearly 4-fold increase in hazard of progression (HR 3.69, 95% CI: 0.978-13.915), with a trend of significance ( P -value 0.0539). Conclusions: In our cohort, grade ≥3 lymphopenia during/after radiotherapy did not emerge as a significant prognostic factor for tumor recurrence. However, several confounding variables may have influenced this outcome. To precisely assess the impact of lymphopenia on pediatric medulloblastoma prognosis, larger-scale prospective studies with extended follow-up are required.