Lymphopenia in Pediatric Patients Following Proton Radiotherapy.

PURPOSE/OBJECTIVE(S) The role of lymphocytes in the body's immune response to cancer cells is increasingly appreciated. While lymphocytes are sensitive to even low doses of radiotherapy (RT), we hypothesized that modern techniques such as proton therapy and vertebral-body sparing craniospinal irradiation (CSI) may minimize RT-associated lymphopenia in pediatric patients. MATERIALS/METHODS Retrospective data from pediatric patients treated with RT at two institutions was reviewed. Blood counts, including lymphocytes, hemoglobin, and platelets, immediately before (pre-RT) and after RT (post-RT) were recorded when available. To assess the impact of vertebral body sparing CSI, vertebral bodies were retrospectively contoured to determine mean vertebral body dose. Patients were divided into CSI, non-CSI CNS, and extracranial groups. Patient and treatment variables were assessed for associations with change in lymphocytes during treatment. RESULTS One-hundred seventy-six pediatric patients treated with RT from 2016-2020 were reviewed. All patients were treated with protons. Of these, 91 had pre-RT and post-RT labs available for review, including 32 CSI, 8 non-CSI CNS, and 51 extracranial treatments. For all patients, 69% had clinical lymphopenia (≤1.6 × 109 lymphocytes/L) prior to RT and 92% had lymphopenia following RT. For the entire cohort, 91% had a reduction in lymphocytes RT, including 97% of CSI and 86% of extracranial treatments. and post-RT. Factors associated with lymphopenia following RT included CSI, multifocal disease, prior surgery, and prior chemotherapy. Post-RT lymphopenia occurred in 100% of patients who received concurrent chemotherapy and 87% of those who did not (P = 0.026). The magnitude of lymphocyte reduction was 50% from pre to post RT (P < 0.001) for all patients, and 58% for CSI patients (P < 0.001). Hemoglobin decreased in 71.4% of patients after RT, including 72% of CSI and 86.3% of extracranial treatments. Platelet count decreased in 89%, including 94% of CSI and 86% of extracranial treatments. Of the 32 patients treated with CSI, 15 were treated with a vertebral body sparing technique as they had reached skeletal maturity. The mean vertebral body dose was 1573cGy for vertebral sparing patients and 2820cGy for others. Higher mean vertebral body dose was associated with greater reduction in lymphocytes from baseline (P = 0.022). There was no association between pre or post RT lymphocytes or magnitude of lymphocyte reduction with survival for the entire cohort. CONCLUSION While lymphopenia is common after RT, modern techniques that spare bone marrow or blood volume, such as proton therapy and vertebral body sparing, may help minimize post-RT lymphopenia. Vertebral body sparing proton CSI demonstrated improvement in post-RT lymphopenia relative to standard proton CSI.