Evaluation of long-term immune system functions in children receiving spleen and abdomen radiotherapy

Introduction and Objective: Hodgkin Lymphoma (HL) constitutes 6.9% of childhood cancers in our country and its survival rates are progressively increasing with newly developed treatment modalities. Studies on the early detection and prevention of long-term treatment-related complications are continuing. The aim of this study is to investigate the presence of long-term radiation-related hyposplenism and immune system dysfunction in HL patients. We also aim to assess infection rates and evaluate the need for preventive measures like vaccination, antibiotic prophylaxis, and infection control in pediatric patients receiving spleen radiation therapy. Materials and Methods: The study included 20 HL patients who had undergone abdominal radiation therapy and completed treatment at least 1 year prior, under follow-up at Istanbul University-Cerrahpaşa Department of Pediatric Hematology-Oncology since 2010 and 20 cases without underlying immunedeficiency but with chronic immune thrombocytopenic purpura, hereditary spherocytosis, or trauma-related splenectomy performed by the Department of Pediatric Surgery at Istanbul University-Cerrahpaşa since 2010 were included. Additionally, 20 healthy controls without underlying chronic diseases or active infections who presented to Istanbul University-Cerrahpaşa General Pediatric and Adolescent Clinic, were also enrolled. Patient demographics, treatment/surgical details, laboratory investigations at diagnosis/presentation, and imaging findings of the patients were recorded. History of prior infections, hospitalizations, positive blood cultures, and vaccination status were obtained. Peripheral blood smears were performed to investigate Howell-Jolly bodies. Venous blood samples were collected from patients to investigate immune system dysfunction, including complete blood count, immunoglobulin levels, and flow cytometry for immune phenotyping, B lymphocyte subgroups, and marginal zone B lymphocyte analysis. Results: In our study, Howell-Jolly bodies were observed in the peripheral smears of 10% of patients in HL group and 90% of patients in the splenectomy group. In the HL group, low levels of IgG were detected in 10% of patients, IgA in 5%, and IgM in 15%. In the splenectomy group, 5% of patients had low IgG levels and 25% had low IgM levels. There was no statistically significant difference in immunoglobulin levels between the two groups. Absolute lymphocyte subset counts in the HL group did not show statistically significant differences compared to healthy controls. However, in the splenectomy group, total B cell, NK cell, and Memory T cell counts were statistically significantly higher (p=0.01, p=0.01, and p=0.001, respectively) compared to healthy controls. When comparing the HL and splenectomy groups, helper T cell and memory T cell absolute counts were statistically significantly lower in the HL group (p=0.01 and p=0.001, respectively). Compared to age-based normal lymphocyte subset counts in healthy Turkish children, 20% of HL patients had lower total T cell and Helper T cell counts, and 10% had decreased Naive T cell counts. In the splenectomy group, 5% showed reduced Helper T cell counts. When evaluating B cell subsets and marginal zone B cell percentage among the groups, statistically significant differences were found in switched memory B cells, non-switched memory B cells, and marginal zone B cells (p=0.046, p=0.0001, and p=0.0001, respectively). HL patients had a statistically significant lower percentage of non-switched memory B cells compared to healthy controls (p=0.0001). In the splenectomy group, both non-switched memory B cells and marginal zone B cell percentages were statistically significantly lower compared to healthy controls (p=0.001 and p=0.0001, respectively). The percentage of marginal zone B cells was lowest in the splenectomy group, followed by the HL group, and highest in the healthy control group. There was no statistically significant dose-response relationship between the radiation dose and the percentage of marginal zone B cells (p=0.325). Regarding vaccination frequency in the splenectomy group, 100% of patients received meningococcal and Hib vaccines preoperatively, while 5% did not receive pneumococcal vaccine. Five years later, only 9% of patients who underwent splenectomy ≥5 years ago received the required booster doses of pneumococcal and meningococcal vaccines. Influenza vaccine was administered to only 10% of patients. When evaluating infection frequency among the groups, it was observed that 15% of patients in the splenectomy group and 20% in the HL group experienced serious infections requiring hospitalization at least 1 year after treatment/surgery. One patient in the splenectomy group had a positive blood culture. Conclusion: The findings of our study support the presence of hyposplenism and immune system dysfunction in HL patients treated with splenic radiation therapy. Implementing preventive measures such as vaccination and antibiotic prophylaxis, similar to those planned for asplenic patients, may be effective in reducing long-term infection-related mortality and morbidity in these cases.