X-linked lymphoproliferative disease type 1 (XLP1) is a primary immunodeficiency disorder caused by pathogenic variants in the SH2D1A gene (SH2 domain containing protein 1A). Patients with XLP1 may present acutely with fulminant infectious mononucleosis, hemophagocytic lymphohistiocytosis, and/or B-cell non-Hodgkin lymphoma (B-NHL). We report a boy who developed 2 clonally distinct B-NHL 4 years apart and was found to have previously unrecognized XLP1. The report highlights the importance of clonal analysis and XLP1 testing in males with presumed late recurrences of B-NHL, and the role of allogeneic stem cell transplant (allo-SCT) in XLP1 patients and their affected male relatives.
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