PURPOSE OF THE STUDY.
To examine the efficacy of transfusion of autologous genetically modified hematopoietic stem cells for Wiskott-Aldrich syndrome (WAS). WAS is an X-linked recessive primary immunodeficiency disorder associated with thrombocytopenia, eczema, and autoimmunity.
Two 3-year-old boys with WAS were included. Inclusion criteria included severe WAS, no evidence of malignancy, and isolation of sufficient numbers of CD34+ cells.
Autologous CD34+ cells were collected by leukopheresis. The cells were then transduced with WAS protein (WASP)-expressing retroviral vectors. The subjects were infused with busulfan. The cells were reinfused back into the subjects 4 days after they were transduced.
WASP expression was demonstrated in a variety of subgroups of leukocytes. At the level of hematopoietic stem cells in the bone marrow, stable chimerism of cells expressing WASP was demonstrated in both subjects. An increase in platelet counts was found starting 6 to 9 months after gene therapy. Improvement was also demonstrated in the function of a variety of subgroups of leukocytes, including natural killer cells, monocytes, T lymphocytes, and B lymphocytes. The frequency and severity of infection decreased in both patients. Signs and symptoms of autoimmunity and eczema disappeared. Comprehensive insertion-site analysis showed vector integration that targeted multiple genes controlling growth and immunologic responses in a persistently polyclonal hematopoiesis. These subjects had been followed for 3 years at the time of the report, and no clonal imbalance (indicating possible neoplastic growth) has been detected.
This study found that gene therapy for WAS is feasible and effective and, during the time of observation, is not associated with treatment-limiting adverse events.
Add WAS to the list of disorders, including severe combined immunodeficiency, chronic granulomatous disease, and adrenoleukodystrophy, that have been treated with gene therapy. These results are fascinating and exciting.
- Copyright © 2011 by the American Academy of Pediatrics