The impact of immunoarchitectural patterns on clinical presentation and response to therapy in children with nodular lymphocyte predominant Hodgkin lymphoma

   In recent years, there has been a trend towards de-escalation of therapy in patients with early stages of nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) which enables reduction in the frequency of late effects of chemo- and radiation therapy while still maintaining their effectiveness. Patients with stage I NLPHL only require excisional biopsy of lymph nodes. If complete remission cannot be achieved by surgery alone or if patients have stage II NLPHL, 3 cycles of low-dose CVP (cyclophosphamide, vinblastine, prednisolone) chemotherapy are administered. In some cases, patients show incomplete response to therapy with subsequent progression of the disease. Hence, the search for factors of unfavorable clinical course of NLPHL still continues, with an immunoarchitectural pattern potentially being one of them.   Here, we aimed to compare clinical features, treatment responses and relapse rates in patients with NLPHL based on the type of an immunoarchitectural pattern.   The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. In our study, we included a cohort of 49 patients (39 boys, 10 girls) aged 2 to 18 years (median age: 10 years) with diagnosed NLPHL who were divided into 2 groups based on histological features of the disease: typical patterns (n = 21, 42.9 %) and atypical patterns (n = 28, 57.1 %). The two groups were compared using the exact Fisher test. Thirty-three patients had early stage I–II disease at baseline, 14 patients had stage III disease, and 2 patients were diagnosed with stage IV lymphoma affecting the liver and lungs in one case and bones in the other. Clinical characteristics (such as disease stage, B symptoms, the involvement of mediastinal and intra-abdominal lymph nodes) didn’t vary much between the groups, the only exception being the presence/absence of bulky disease (≥ 6 cm) (p = 0.0064). A higher rate of partial response to therapy and disease progression frequency were revealed in the group of atypical patterns (typical: n = 1/21, 4.8 % vs atypical: n = 14/28, 50 %; p = 0.00061). This group was also characterized by a higher relapse rate (typical patterns: n = 1/21, 4.8 % vs atypical: n = 5/28, 17.9 %; p = 0.219). The overall survival rate was 100%, with a median follow-up of 28 (3–108) months. In our study, we revealed a higher incidence of adverse outcomes in the patients with atypical NLPHL patterns compared to the group with typical patterns. The prognostic value of immunoarchitectural patterns needs to be explored more thoroughly, as they have the potential to become one of the criteria for risk stratification of patients with NLPHL.