The Natural History of X-Linked Lymphoproliferative Disease (XLP1): Lessons from a Long-Term Survivor

Abstract

X-linked lymphoproliferative disease (XLP1) is a rare primary immunodeficiency characterized by EBV-triggered immune dysregulation, lymphoproliferation, dysgammaglobulinemia, and lymphoma. Early childhood mortality from overwhelming inflammation is expected in most patients. The only curative therapy is hematopoietic stem cell transplant (HSCT); however, whether to perform HSCT on an asymptomatic patient remains debatable. This uncertainty arises because the natural history of XLP1 patients without transplantation is not clear. In this case report, we present the natural history of XLP1 in a 43-year-old male patient who did not receive HSCT. We also review the literature on untransplanted XLP1 patients who lived into mid-adulthood. Despite surviving childhood presentations that are typically fatal, we found that these rare patients remain susceptible to manifestations of XLP1 decades later.

Case Report: Meningoencephalitis With Thrombotic Occlusive Vasculopathy in a Young EBV-Naïve Boy Is Associated With a Novel SH2D1A Mutation

“…Approximately one third of the patients were reported to have lymphoproliferative disorders and one third were observed to have antibody deficiency (5,6). Other rare but well-described clinical features include lymphoma, aplastic anemia, chronic gastritis, lymphomatoid granulomatosis and lymphocytic vasculitis (7)(8)(9)(10). Due to diverse clinical symptoms and EBV-seronegativity in approximately 10% of the patients, early diagnosis of SH2D1A deficiency as the causative condition is challenging (5).…”

Development of EBV Related Diffuse Large B-cell Lymphoma in Deficiency of Adenosine Deaminase 2 with Uncontrolled EBV Infection

“…EBV related haematological neoplasms including DLBCL can occur in the setting of chronic EBV infection due to impaired T cell surveillance. Lymphomas with similar a phenotype have been identified in other inborn errors of immunity including Wiskott Aldrich Syndrome and X-linked lymphoproliferative disease 1 and DOCK8 deficiency [ 5 , 11 , 12 ].…”

Lymphoproliferation in Inborn Errors of Immunity: The Eye Does Not See What the Mind Does Not Know

“…The reported cases are mostly EBV-positive HL, DLBCL, and BL ( 41 ). XLP1 associated LP ranges from non-malignant LP including lymphoid interstitial pneumonia, LYG, cerebral lymphocytic vasculitis, HLH, and severe IM, to malignant lesions like HL, DLBCL, CNS DLBCL, and BL ( 47 ). Patients with 4-1BB deficiency have been diagnosed with EBER+ HL and CD20-CD38+ DLBCL on lymph node biopsies ( 48 ).…”