Abstract: Background: Childhood lymphoma with SH2D1A gene mutation is rare in clinical practice and has special clinical features and prognosis. Objective:To summarize the clinical manifestations, pathological features, treatment and prognosis of childhood lymphoma with SH2D1A gene mutation. Design:Case series report. Methods:Consecutive hospitalized patients who were newly diagnosed with lymphoma under the age of 18 and had SH2D1A gene mutation indicated by highthroughput whole exon gene sequence were enrolled from Beijing Children's Hospital affiliated to Capital Medical University between June 2017 and July 2022. The treatment plan was determined according to the pathological diagnosis. Invasive mature Bcell lymphoma was treated based on the modified LMB89 regimen. Mature Tcell lymphoma complicated with hemophagocytic syndrome(HLH) was first controlled by the HLH regimen, and chemotherapy was given after the diagnosis by the SMILE regimen. The efficacy was evaluated in the middle period after 2 to 3 months of chemotherapy. Ultrasound and PET/CT were performed at 3 months after chemotherapy. Tumor ultrasound, liver function, LDH and immune function were tested every 3 months within 1 and 2 years after chemotherapy. Main outcome measures:Clinical characteristics and prognosis of children lymphoma with SH2D1A gene mutation. Results:A total of six male patients of childhood lymphoma with SH2D1A gene mutation were summarized. The median age of onset was 5(412) years. The tumor lesions involved the gastrointestinal tract in 3 cases, central nervous system, head and neck, and multiple organs in 1 case each. In terms of clinical stages, there was 1 case of stage Ⅱ, 3 cases of stage Ⅲ, and 2 cases of stage Ⅳ. For pathological types, 3 cases were for diffuse large Bcell lymphoma, 1 case for highgrade mature Bcell lymphoma, 1 case for Burkittlike lymphoma with 11q abnormality, and 1 case for systemic EpsteinBarr virus positive Tcell lymphoma in children. Humoral immunity and/or cellular immunity decreased in 5 cases. Whole blood and plasma EBVDNA were negative in 5 cases at the beginning of the disease, and whole blood EBVDNA increased to ≥105 copy number /mL during the course of the disease in 2 of them. One patient had familial HLH at the beginning of the disease, with multiple whole blood EBVDNA of 106 copies/mL. Six cases showed SH2D1A gene mutation, among which 2 cases showed no abnormal SAP protein detection; 1 case had chromosomal abnormality; 3 cases completed chemotherapy; 2 cases died due to hemophagocytic syndrome, and 1 case received rituximab immunotherapy. Conclusion:Lymphoma in children with SH2D1A gene mutation is rare in clinical practice. The main pathological manifestation is nonHodgkin lymphoma (mature Bcell lymphoma), and the prognosis is poor. Allogeneic hematopoietic stem cell transplantation may improve the prognosis of the disease when there is a need.

Key words: SH2D1A gene mutation, Childhood lymphoma, X-linked lymphoproliferative syndrome type 1