Hematopoietic Stem Cell Transplantation for X-Linked Thrombocytopenia With Mutations in the WAS gene

J Clin Immunol. 2015 Jan;35(1):15-21. doi: 10.1007/s10875-014-0105-5. Epub 2014 Nov 12.

Abstract

X-linked thrombocytopenia (XLT) is a mild form of the Wiskott-Aldrich syndrome (WAS) caused by mutations in the WAS gene. A recent retrospective study of the clinical outcome and molecular basis of a large cohort of XLT patients demonstrated that although overall survival is excellent, event free survival is severely affected with conservative treatment. To answer the question whether hematopoietic stem cell transplantation (HSCT) offers a viable alternative therapeutic option in XLT, we retrospectively investigated the outcome of HSCT in a cohort of 24 XLT patients who received HSCT between 1990 and 2011 at 14 transplant centers in the United States, Italy, Germany, Canada, and Japan. The engraftment rate was 100% and the overall survival rate was 83.3%. Of the four non-survivors, 2 underwent splenectomy prior to HSCT and died of sepsis, and two of aspergillus infections associated with severe GVHD. In all but one patient, pretransplant complications were resolved by HSCT. Our data indicate that HSCT following myeloablative conditioning is curative and associated with acceptable risks as a treatment option for XLT.

Keywords: Wiskott-Aldrich syndrome; X-linked thrombocytopenia; hematopoietic stem cell transplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Cohort Studies
  • Disease-Free Survival
  • Genetic Diseases, X-Linked / genetics*
  • Genetic Diseases, X-Linked / mortality
  • Genetic Diseases, X-Linked / therapy*
  • Graft vs Host Disease / etiology
  • Hematopoietic Stem Cell Transplantation* / adverse effects
  • Humans
  • Infant
  • Kaplan-Meier Estimate
  • Male
  • Mutation*
  • Retrospective Studies
  • Thrombocytopenia / genetics*
  • Thrombocytopenia / mortality
  • Thrombocytopenia / therapy*
  • Wiskott-Aldrich Syndrome / genetics
  • Wiskott-Aldrich Syndrome Protein / genetics*
  • Young Adult

Substances

  • WAS protein, human
  • Wiskott-Aldrich Syndrome Protein

Supplementary concepts

  • Thrombocytopenia 1