Hematopoietic stem cell gene therapy of Wiskott Aldrich Syndrome.

KAAN BOZTUG; RICARDO A. DEWEY; INES AVEDILLO DÍEZ; MANFRED SCHMIDT; KERSTIN SCHWARZWAELDER; LAZLO MARODI; IRINA KONDRATENKO; JANA DIESTELHORST; SONJA NAUNDORF; KLAUS KUEHLKE; CHRISTOPH VON KALLE; KARL WELTE; CHRISTOPH KLEIN

Rotterdam

Congreso; 15th Annual Meeting of the European Society of Gene and Cell Therapy (ESGCT); 2007

European Society of Gene and Cell Therapy (ESGCT)

Wiskott Aldrich Syndrome (WAS) is a fatal primary immunodeficiency disorder caused by mutations in WASP. We here report on our preliminary experience with two patients undergoing hematopoietic stem cell gene therapy upon retroviral WASP gene transfer. The patients were treated with 8x106 and 7x106 /kg body weight transduced CD34 cells, respectively. Follow-up time is 9 and 10 months. Both patients show gene evidence of gene marking and WAS protein expression in multiple hematopoietic lineages. In particular, WASP-transgenic T and NK cells show an increase over time. At the present time, both patients show a polyclonal pattern of hematopoiesis, as determined by LAM-PCR. No morphological or cytogenetic abnormalities were observed in the bone marrow. While one patient continues to suffer from autoimmune cytopenia, the other patient has had a marked clinical benefit. This interim analysis documents that hematopoietic gene therapy for WAS is feasible without undue short term toxicity. A longer follow-up period will be required to comprehensively evaluate the clinical and molecular outcome in these patients and to monitor for potential unwanted side-effects.