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.

Rare solid tumors in a patient with Wiskott–Aldrich syndrome after hematopoietic stem cell transplantation: case report and review of literature

“…Risk factors for post-transplant autoimmunity appears to be donor type, with a higher incidence detected in matched unrelated donors, and mixed chimerism, especially on myeloid cells, although this trend does not appear to be confirmed in the long-term follow-up ( 12 ). While the incidence of autoimmunity is estimated to be 20% within the first 2 years after transplantation, the incidence of hematopoietic or solid tumors in WAS patients after transplantation is not well defined ( 32 ). Patients who underwent HSCT for reasons different from WAS had a risk of solid tumors significantly higher than the general population.…”

Inborn errors of immunity with kidney and urinary tract disorders: a review

“…X-linked Wiskott–Aldrich syndrome (WAS), first recognized in 1937 by Dr. Alfred Wiskott, and then in 1957, confirmed by Robert Aldrich [ 39 ].it is estimated to involve 1–10 live births per million males. The WAS gene encodes a cytosolic protein known as WAS protein (WASp) and it expressed in myeloid, lymphoid, and hematopoietic stem cells (HSCs), which can lead to various clinical manifestations, but thrombocytopenia (X-linked thrombocytopenia [XLT]), eczema, and recurrent infections with increased risk of lymphoid malignancies, autoimmune disorders or congenital neutropenia (X-lined neutropenia [XLN]) are classic phenotype of WAS [ 40 , 41 ]. The patients with thrombocytopenia show a different range of symptoms from a mild petechiae and purpura to serious intracranial and/or intestinal bleeding, which lead to death in 4–10%.…”

“…The mean platelet volume (MPV) in WAS is often < 5 fL, so it can reach < 2 fL in the patients with severe bleeding symptoms. In addition, this disease is usually misdiagnosed with immune thrombocytopenia (ITP), and it should be noted that the WAS hallmark is micro thrombocytopenia (small platelets) [ 41 ]. Eczema can affect 75% of these patients, and usually shows itself as refractory and the patient is not able to treat it quickly [ 42 ].…”

Tailored treatments in inborn errors of immunity associated with atopy (IEIs-A) with skin involvement

“…WAS treatment strategies consist of supportive measures, hematopoietic stem cell transplantation (HSCT) and gene therapy. Immunosuppressive/immunomodulatory drugs to control autoimmune diseases linked to WAS include corticosteroids, intravenous immunoglobulin (IVIG), rituximab, cyclophosphamide, azathioprine, and calcineurin inhibitors ( 8 ). With regard to the dermatitis the treatment is based on topical emollients, corticosteroids and according to some authors antiseptic baths ( 3 ).…”