Blood Journal
Leading the way in experimental and clinical research in hematology

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

  1. Claire Booth1,
  2. Kimberly C. Gilmour1,
  3. Paul Veys1,
  4. Andrew R. Gennery2,
  5. Mary A. Slatter2,
  6. Helen Chapel3,
  7. Paul T. Heath4,
  8. Colin G. Steward5,
  9. Owen Smith6,
  10. Anna O'Meara6,
  11. Hilary Kerrigan6,
  12. Nizar Mahlaoui7,
  13. Marina Cavazzana-Calvo7,
  14. Alain Fischer7,
  15. Despina Moshous7,
  16. Stephane Blanche7,
  17. Jana Pachlopnik-Schmid7,
  18. Sylvain Latour8,
  19. Genevieve de Saint-Basile8,
  20. Michael Albert9,
  21. Gundula Notheis9,
  22. Nikolaus Rieber9,
  23. Brigitte Strahm10,
  24. Henrike Ritterbusch11,
  25. Arjan Lankester12,
  26. Nico G. Hartwig13,
  27. Isabelle Meyts14,
  28. Alessandro Plebani15,
  29. Annarosa Soresina15,
  30. Andrea Finocchi16,
  31. Claudio Pignata17,
  32. Emilia Cirillo17,
  33. Sonia Bonanomi18,
  34. Christina Peters19,
  35. Krzysztof Kalwak20,
  36. Srdjan Pasic21,
  37. Petr Sedlacek22,
  38. Janez Jazbec23,
  39. Hirokazu Kanegane24,
  40. Kim E. Nichols25,
  41. I. Celine Hanson26,
  42. Neena Kapoor27,
  43. Elie Haddad28,
  44. Morton Cowan29,
  45. Sharon Choo30,
  46. Joanne Smart30,
  47. Peter D. Arkwright31, and
  48. Hubert B. Gaspar1,*
  1. 1 Center of Immunodeficiency, Molecular Immunology Unit, Institute of Child Health, London, United Kingdom;
  2. 2 Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom;
  3. 3 Department of Clinical Immunology, Nuffield Department of Medicine, University of Oxford and Oxford Radcliffe Hospitals, Oxford, United Kingdom;
  4. 4 St. George's Hospital, London, United Kingdom;
  5. 5 Bone Marrow Transplant Unit, Royal Hospital for Children, Bristol, United Kingdom;
  6. 6 Department of Haematology & Oncology, Our Lady's Children's Hospital, Dublin, Ireland;
  7. 7 Unite d'Immuno-Hematologie et Rhumatologie Pediatrique, Hopital Necker-Enfants Malades, Assistance Publique-Hopitaux de Paris, Paris, France;
  8. 8 INSERM U678, Hopital Necker-Enfants Malades, Paris, France;
  9. 9 Department of Pediatric Hematology/Oncology and Infection/Immunity, Dr. von Haunersches Kinderspital, Munich, Germany;
  10. 10 Department of Pediatric Hematology and Oncology, Center for Pediatric and Adolescent Medicine, University of Freiburg, Germany;
  11. 11 Centre for Chronic Immunodeficiency (CCI), University Medical Center Freiburg, Germany;
  12. 12 Department of Pediatrics, Division of Immunology, Haematology, Oncology, Bone Marrow Transplantation and Autoimmune Diseases, Leiden University Medical Center, Leiden, Netherlands;
  13. 13 Department of Paediatric Infectious Disease and Immunology, Erasmus Medical Center, Sophia Children's Hospital, Rotterdam, Netherlands;
  14. 14 Department of Paediatrics, University Hospital Leuven, Leuven, Belgium;
  15. 15 Department of Paediatrics, University of Brescia, Brescia, Italy;
  16. 16 Dept of Pediatrics, Unit of Immunoinfectivology, Children's Hospital Bambino Gesu, Tor Vergata University, Rome, Italy;
  17. 17 Department of Pediatrics, "Federico II" University, Naples, Italy;
  18. 18 Clinica Pediatrica dell'Universita di Milano-Bicocca, Centro Trapianto di Midollo Osseo, Ospedale San Gerardo, Monza, Italy;
  19. 19 BMT Unit, St. Anna Children's Hopsital, Vienna, Austria;
  20. 20 Department of Paediatric Haematology and Oncology, Medical University of Wroclaw, Wroclaw, Poland;
  21. 21 Departments of Paediatric Immunology, Pathology and Transfusion Medicine, Mother and Child Health Institute Dr Vukan Cupic, Belgrade, Serbia;
  22. 22 Department of Paediatric Haematology and Oncology, University Hospital Motol, Charles University, Prague, Czech Republic;
  23. 23 Division of oncology and hematology, Department of Pediatrics, Medical Center, Ljubljana, Slovenia;
  24. 24 Department of Paediatrics, Graduate School of Medicine, University of Toyama, Toyama, Japan;
  25. 25 Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, United States;
  26. 26 Department of Pediatrics, Texas Children's Hospital, Baylor College of Medicine, Houston, United States;
  27. 27 Division of Research Immunology/BMT, Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, United States;
  28. 28 Department of Pediatrics, and Microbiology and Immunology, CHU Sainte-Justine, Universite de Montreal, Montreal, Quebec, Canada;
  29. 29 Pediatric Blood and Marrow Transplant Division, UCSF Children's Hospital, San Francisco, California, United States;
  30. 30 Department of Allergy and Immunology, Royal Children's Hospital, Parkville, Victoria, Australia;
  31. 31 University of Manchester, Royal Manchester Children's Hospital, Manchester, United Kingdom
  1. * Corresponding author; email: h.gaspar{at}ich.ucl.ac.uk
This article has an Erratum 118(18):5060

Abstract

X-linked lymphoproliferative disease (XLP1) is a rare immunodeficiency characterised by severe immune dysregulation and caused by mutations in the SH2D1A/SAP gene. Clinical manifestations are varied and include hemophagocytic lymphohistiocytosis (HLH), lymphoma and dysgammaglobulinaemia, often triggered by Epstein-Barr virus (EBV) infection. Historical data published prior to 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 following allogeneic HSCT is 81.4% with good immune reconstitution in the large majority of patients and little evidence of post-transplant 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 since 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.

  • Submitted June 10, 2010.
  • Accepted September 19, 2010.