Article open access publication

Wiskott-Aldrich Syndrome: A Retrospective Study on 575 Patients Analyzing the Impact of Splenectomy, Stem Cell Transplantation, or No Definitive Treatment on Frequency of Disease-Related Complications and Physician-Perceived Quality of Life

Blood, American Society of Hematology, ISSN 1528-0020

Volume 128, 22, 2016

DOI:10.1182/blood.v128.22.366.366, Dimensions: pub.1122673949,


Liu, Dawei (39)



  1. (1) Klinikum der Universität München, grid.411095.8
  2. (2) University of Washington, grid.34477.33
  3. (3) San Raffaele Hospital, grid.18887.3e
  4. (4) University of Manchester, grid.5379.8
  5. (5) Dmitry Rogachev Federal Research Centre of Pediatric Hematology, Oncology and Immunology, Moscow, Russian Federation
  6. (6) Technical University of Munich, grid.6936.a
  7. (7) Ludwig Maximilian University of Munich, grid.5252.0
  8. (8) Spedali Civili di Brescia, grid.412725.7
  9. (9) Children's Hospital of Orange County, grid.414164.2
  10. (10) University Hospitals of Leicester NHS Trust, grid.269014.8
  11. (11) Shupyk National Medical Academy of Postgraduate Education, grid.415616.1
  12. (12) University Hospital of Lausanne, grid.8515.9
  13. (13) Azienda Ospedaliera San Gerardo, grid.415025.7
  14. (14) University of Alabama at Birmingham, grid.265892.2
  15. (15) University Hospital Bratislava, grid.412685.c
  16. (16) Royal Children's Hospital, grid.416107.5
  17. (17) Federal University of Sao Paulo, grid.411249.b
  18. (18) Department of Pediatrics, University Children's Hospital of Cracow, Cracow, Poland
  19. (19) Helios Klinikum Krefeld, grid.506258.c
  20. (20) Regional Immunology Service, The Royal Hospitals, Belfast, United Kingdom
  21. (21) Pediatric BMT Unit, Bahcelievler Medicalpark Hospital, Istanbul, Turkey
  22. (22) University of Gothenburg, grid.8761.8
  23. (23) University Hospital in Motol, grid.412826.b
  24. (24) Centre of Cardiovascular and Transplantation Surgery, Brno, Czech Republic
  25. (25) Meyer Children's Hospital, grid.413181.e
  26. (26) University of Florence, grid.8404.8
  27. (27) Great North Children's Hospital, grid.459561.a
  28. (28) Hospital Universitario 12 De Octubre, grid.144756.5
  29. (29) Federal University of Minas Gerais, grid.8430.f
  30. (30) Kuopio University Hospital, grid.410705.7
  31. (31) University Hospital Ulm, grid.410712.1
  32. (32) Oulu University Hospital, grid.412326.0
  33. (33) University of Toyama, grid.267346.2
  34. (34) Turku University Hospital, grid.410552.7
  35. (35) Ege University, grid.8302.9
  36. (36) Uludağ University, grid.34538.39
  37. (37) Collegium Medicum in Bydgoszcz, grid.411797.d
  38. (38) Russian Children's Clinical Hospital, grid.459888.0
  39. (39) Chongqing Medical University, grid.203458.8
  40. (40) St Anna Children's Hospital, grid.416346.2
  41. (41) Universitair Ziekenhuis Leuven, grid.410569.f
  42. (42) John Radcliffe Hospital, grid.8348.7
  43. (43) Azerbaijan Medical University, grid.411469.f
  44. (44) Hospital Universitari Vall d'Hebron, grid.411083.f
  45. (45) Mother and Child Health Institute, Belgrad, Serbia
  46. (46) Centre Hospitalier Universitaire d'Angers, grid.411147.6
  47. (47) University of Naples Federico II, grid.4691.a
  48. (48) Rigshospitalet, grid.475435.4, Capital Region
  49. (49) Federal University of Uberlândia, grid.411284.a
  50. (50) Clinical and Research Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russian Federation
  51. (51) Center for Biologics Evaluation and Research, grid.290496.0
  52. (52) Hadassah Medical Center, grid.17788.31
  53. (53) University Medical Center Utrecht, grid.7692.a
  54. (54) Helsinki Children's Hospital, grid.424592.c
  55. (55) Children's Memorial Health Institute, grid.413923.e
  56. (56) Children's Hospital of Chongqing Medical University, grid.488412.3
  57. (57) Sydney Children's Hospital, grid.414009.8


Abstract Background: The Wiskott-Aldrich syndrome (WAS) including X-linked thrombocytopenia (XLT) is a complex disorder with a wide range of disease severity and unique hematological and immunological manifestations. Based on this complexity, several approaches are available to these patients, including observation, symptomatic treatment, splenectomy, gene therapy (GT), or allogeneic hematopoietic stem cell transplantation (HSCT). In many instances more than one of these therapeutic options may seem appropriate for any given patient. A prospective, randomized study comparing the pros and cons of these therapeutic options in WAS/XLT would be desirable, but is not feasible due to the rarity and variable severity of the disease, as well as the need for long-term follow-up. Methods and Definitions: We retrospectively assessed via an international, anonymized, file-based survey the consequences of different therapies based on the severity of the disease phenotype and how these therapies affected patients' quality of life as perceived by their treating physician. The frequency of disease- and therapy-related complications with respect to the specific treatment was recorded. "Severe events" were defined as: all fatal events or sepsis, meningitis, pneumonia requiring respiratory support, systemic viral/fungal infections or serious bleeding episodes (intracranial and gastrointestinal) requiring transfusion support. Allogeneic HSCT, splenectomy and GT were defined as "procedures", HSCT and GT as "definitive". Results: A total of 575 patients with a documented WAS gene mutation from 51 centers in 27 countries with a median follow-up of 7.4 years (range: 0.2-75.6), resulting in 5632 patient years, were included in the study. Of these, 240 (42%) carried missense, 67 (12%) nonsense, 90 (16%) splice-site mutations, 77 (13%) deletions, 40 (7%) insertions and 61 (11%) had incomplete or inconclusive mutation information. An allogeneic HSCT was performed in 252 (44%), splenectomy in 78 (14%), GT in 14 (2%) patients, while 264 (46%) patients never had a procedure. At the time of last follow-up or before the first procedure the WAS disease severity score was 1 in 55 (10%), 2 in 144 (25%), 3 in 161 (28%), 4 in 109 (19%) and 5 in 86 (15%) patients. Overall survival of the entire cohort (censored at the time of first definitive procedure, thereby representing the "natural" disease outcome) was 82% (95% confidence interval 78-87) at 15 years and 70% (61-80) at 30 years of age. Ten year overall survival after HSCT was 80 % (74-85). The cumulative incidence (CI) of severe bleeding, severe infection, autoimmunity or malignancy in patients without a procedure at last follow-up or censored before the first procedure was 45% (39-50), 61% (55-66), 46% (40-52) and 31% (25-37) respectively at 15 years of age and 61% (51-69), 70% (62-76), 62% (52-70) and 45% (35-53) at 30 years. The frequency of definitive procedures (HSCT or GT) increased in patients with higher WAS scores, while better natural disease outcomes were associated with lower WAS scores. Overall quality of life (QoL) as perceived by the treating physician was very good, good, limited or unacceptable in 85/457 (19%), 172/457 (38%), 176/457 (39%) and 24/457 (5%) of patients without or before a procedure respectively. QoL was also strongly correlated with the WAS score. At last follow-up after successful HSCT QoL improved to very good in 123/184 (67%), good in 47/184 (26%), limited in 12/184 (7%) and unacceptable in 2/184 (1%). Splenectomy also had a favorable effect on QoL with 16/52 (31%) very good, 24/52 (46%) good, 9/52 (17%) limited and 3/52 (6%) unacceptable. Platelet counts improved from a baseline mean of 36G/l to 91G/l after GT, 159G/l after splenectomy and 204G/l after HSCT. Conclusion: This study presents outcome data of the largest cohort of patients with a WAS gene mutation studied so far and confirms the anticipated spectrum of disease severity and the curative effect of HSCT. The data show that untreated patients with WAS suffer from increasing rates of disease-associated complications over time which correlates well with a significant reduction of QoL. Both HSCT and splenectomy have a positive effect on physician-perceived QoL. Due to the large cohort size this study's data will allow us to assess the influence of specific genotypes on outcome in WAS (analysis ongoing), possibly allowing for more individualized treatment recommendations in the future. Disclosures Albert: GSK: Research Funding.

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