Clinical Features, Cancer Biology, Transplant Approach and Other Integrated Management Strategies for Wiskott-Aldrich Syndrome

Abstract

Wiskott-Aldrich syndrome (WAS) is a rare X-linked recessive inborn error of immunity (IEI) first described in 1937. Classic WAS is characterized by the triad of thrombocytopenia with small platelets, recurrent infections due to combined immunodeficiency, and eczema. Hematopoietic stem cell transplantation (HSCT) was the only curative option available for five decades, with excellent outcomes reported for matched sibling donors (MSD) and matched unrelated donors (MUD). More recently, alternative donor transplants such as umbilical cord blood (UCB) and haploidentical transplant have emerged as viable options due to improvements in better graft selection, cell dosing, and effective allograft manipulation measures. Gene therapy is another potential curative option with promising results, yet currently is offered only as part of a clinical trial.

Keywords: Wiskott–Aldrich syndrome; X-linked thrombocytopenia; gene therapy; hematopoietic stem cell transplantation; supportive care.

Figure 1

Treatment decision algorithm for WAS/ XLT based on the severity of clinical symptoms, type of genetic mutation, and WASp expression. For patients with classic WAS with a suitable MSD/MUD donor or CB 5-6/6 or 4/6 with a good cell dose, an early transplant should be performed. In the absence of a suitable matched donor, a Haploidentical transplant or gene therapy trial should be discussed. XLT patients with severe thrombocytopenia or mutation suggestive of a severe phenotype and absent WASp expression should also be transplanted.