Long-term outcome following hematopoietic stem-cell transplantation in Wiskott-Aldrich syndrome: collaborative study of the European Society for Immunodeficiencies and European Group for Blood and Marrow Transplantation

Abstract

Wiskott-Aldrich syndrome (WAS) is a rare X-linked immunodeficiency with microthrombocytopenia, eczema, recurrent infections, autoimmune disorders, and malignancies that are life-threatening in the majority of patients. In this long-term, retrospective, multicenter study, we analyzed events that occurred in 96 WAS patients who received transplants between 1979 and 2001 who survived at least 2 years following hematopoietic stem-cell transplantation (HSCT). Events included chronic graft-versus-host disease (cGVHD), autoimmunity, infections, and sequelae of before or after HSCT complications. Three patients (3%) died 2.1 to 21 years following HSCT. Overall 7-year event-free survival rate was 75%. It was lower in recipients of mismatched related donors, also in relation with an older age at HSCT and disease severity. The most striking finding was the observation of cGVHD-independent autoimmunity in 20% of patients strongly associated with a mixed/split chimerism status (P < .001), suggesting that residual-host lymphocytes can mediate autoimmune disease despite the coexistence of donor lymphocytes. Infectious complications (6%) related to splenectomy were also significant and may warrant a more restrictive approach to performing splenectomy in WAS patients. Overall, this study provides the basis for a prospective, standardized, and more in-depth detailed analysis of chimerism and events in longterm follow-up of WAS patients who receive transplants to design better-adapted therapeutic strategies. (Blood. 2008;111: 439-445)

Increasing mixed chimerism and the risk of graft loss in children undergoing allogeneic hematopoietic stem cell transplantation for non-malignant disorders

“…For example, while most children with primary immunodeficiency disorders such as SCID develop normal immune function with a low level of donor chimerism, some children with Wiskott-Aldrich syndrome may require CDC to control symptoms of autoimmunity. 22,23 The incidence of increasing MC was 33% in our study which is within the range of published results. Hoelle et al 4 reported an incidence of 13% in a cohort of children with severe aplastic anemia receiving CD34 þ enriched transplants, and Willasch et al 11 reported a 34% incidence of increasing MC in children with non-malignancies conditioned with busulfan, cyclophosphamide and antithymocyte globulin, 70% of whom received T-cell depleted transplants.…”

Treosulfan-based conditioning regimens for hematopoietic stem cell transplantation in children with primary immunodeficiency: United Kingdom experience

“…Conversely, patients receiving cord blood stem cells in conjunction with serotherapy had a tendency to more mixed donor chimerism. Although donor myeloid chimerism was sufficiently high to cure most patients with CGD and WAS with all donor types/stem cell sources, where 100% donor chimerism might be preferred in all cell lineages (eg, WAS), 25 then the use of PBSCs or full myeloablation with busulfan might be required.…”

Evaluation of Classic Wiskott Aldrich Syndrome with Mild Symptoms in Two Cousins: A Case Report

“…The clinical symptoms are usually severe in those classic WAS patients with chronic eczema and frequent lymphadenopathy and hepatosplenomegaly (1). Moreover, patients with the classic WAS phenotype should be usually treated with allogeneic HSCT (7). It is vital to treat classic WAS patients with severe symptoms and infections as soon as diagnosis is established (8).…”