X-linked lymphoproliferative disease due to SAP/SH2D1A deficiency: a multicenter study on the manifestations, management and outcome of the disease |
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Authors: | Booth Claire Gilmour Kimberly C Veys Paul Gennery Andrew R Slatter Mary A Chapel Helen Heath Paul T Steward Colin G Smith Owen O'Meara Anna Kerrigan Hilary Mahlaoui Nizar Cavazzana-Calvo Marina Fischer Alain Moshous Despina Blanche Stephane Pachlopnik Schmid Jana Pachlopnick-Schmid Jana Latour Sylvain de Saint-Basile Genevieve Albert Michael Notheis Gundula Rieber Nikolaus Strahm Brigitte Ritterbusch Henrike Lankester Arjan Hartwig Nico G Meyts Isabelle Plebani Alessandro Soresina Annarosa Finocchi Andrea Pignata Claudio Cirillo Emilia Bonanomi Sonia Peters Christina Kalwak Krzysztof |
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Institution: | Center of Immunodeficiency, Molecular Immunology Unit, Institute of Child Health, London, United Kingdom. |
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Abstract: | X-linked lymphoproliferative disease (XLP1) is a rare immunodeficiency characterized by severe immune dysregulation and caused by mutations in the SH2D1A/SAP gene. Clinical manifestations are varied and include hemophagocytic lymphohistiocytosis (HLH), lymphoma and dysgammaglobulinemia, often triggered by Epstein-Barr virus infection. Historical data published before improved treatment regimens shows very poor outcome. We describe a large cohort of 91 genetically defined XLP1 patients collected from centers worldwide and report characteristics and outcome data for 43 patients receiving hematopoietic stem cell transplant (HSCT) and 48 untransplanted patients. The advent of better treatment strategies for HLH and malignancy has greatly reduced mortality for these patients, but HLH still remains the most severe feature of XLP1. Survival after allogeneic HSCT is 81.4% with good immune reconstitution in the large majority of patients and little evidence of posttransplant lymphoproliferative disease. However, survival falls to 50% in patients with HLH as a feature of disease. Untransplanted patients have an overall survival of 62.5% with the majority on immunoglobulin replacement therapy, but the outcome for those untransplanted after HLH is extremely poor (18.8%). HSCT should be undertaken in all patients with HLH, because outcome without transplant is extremely poor. The outcome of HSCT for other manifestations of XLP1 is very good, and if HSCT is not undertaken immediately, patients must be monitored closely for evidence of disease progression. |
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