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Multicenter Study
. 2011 Jan 6;117(1):53-62.
doi: 10.1182/blood-2010-06-284935. Epub 2010 Oct 6.

X-linked lymphoproliferative disease due to SAP/SH2D1A deficiency: a multicenter study on the manifestations, management and outcome of the disease

Claire Booth  1 , Kimberly C Gilmour, Paul Veys, Andrew R Gennery, Mary A Slatter, Helen Chapel, Paul T Heath, Colin G Steward, Owen Smith, Anna O'Meara, Hilary Kerrigan, Nizar Mahlaoui, Marina Cavazzana-Calvo, Alain Fischer, Despina Moshous, Stephane Blanche, Jana Pachlopnik Schmid, Sylvain Latour, Genevieve de Saint-Basile, Michael Albert, Gundula Notheis, Nikolaus Rieber, Brigitte Strahm, Henrike Ritterbusch, Arjan Lankester, Nico G Hartwig, Isabelle Meyts, Alessandro Plebani, Annarosa Soresina, Andrea Finocchi, Claudio Pignata, Emilia Cirillo, Sonia Bonanomi, Christina Peters, Krzysztof Kalwak, Srdjan Pasic, Petr Sedlacek, Janez Jazbec, Hirokazu Kanegane, Kim E Nichols, I Celine Hanson, Neena Kapoor, Elie Haddad, Morton Cowan, Sharon Choo, Joanne Smart, Peter D Arkwright, Hubert B Gaspar
Affiliations
Multicenter Study

X-linked lymphoproliferative disease due to SAP/SH2D1A deficiency: a multicenter study on the manifestations, management and outcome of the disease

Claire Booth et al. Blood. .

Erratum in

  • Blood. 2011 Nov 3;118(18):5060. Pachlopnick-Schmid, Jana [corrected to Pachlopnik Schmid, Jana]

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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Figures

Figure 1
Figure 1
Outcome of patients with HLH during course of disease. Survival of patients who present with HLH—patients who remain untransplanted have a poor survival outcome with only 18.8% survival. By contrast the survival of those who undergo transplant is higher at 50%.
Figure 2
Figure 2
Survival in XLP1 related to different variables. (A) Overall survival of transplanted versus untransplanted patients. In the transplanted group this represents time from presentation and not transplant. (B) Survival according to donor source. (C) Survival after HSCT with relation to presence of HLH before transplant. (D) Survival according to age at transplant.
Figure 3
Figure 3
Outcome of patients with SAP/SH2D1A mutations.
See this image and copyright information in PMC

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