The primary purpose of this study is to assess the feasibility and therapeutic efficacy of gene transfer into the hematopoietic stem cells (HSC) of patients with chronic non-spherocytic hemolytic anemia (CNHSA) due to glucose 6-phosphate dehydrogenase (G6PD) deficiency. This gene transfer will provide preliminary evidence of the production of sufficient G6PD to cause improvement in peripheral blood counts and decrease in chronic hemolysis in CNSHA patients. The secondary aim is to evaluate the extent of engraftment and the persistence of the transduced HSC following autologous transplantation without myeloablation in CNSHA patients caused by G6PD deficiency. Furthermore, to provide evidence that the phenotypically corrected cells will have a selective growth advantage over the G6PD deficient host bone marrow. This is an unblinded pilot study using ex vivo transduction with a recombinant retroviral vector to transduce the cording sequence of the human G6PD (GDPD cDNA) into the patients' HSC. The autologous transduced bone marrow will be reinforced without myeloablation. Six patients with CNSHA due to G6PD deficiency will be enrolled. Although patients with severe with severe G6PD deficiency who have CNSHA are rare, they make up, together with pyruvate kinase deficiency, the majority of patients with CNSHA due to an enzymopathy. The current protocol provides a possible cure for patients in this disease without myelosuppressive conditioning or hospitalization. This study would also provide valuable information for other clinical conditions, as the protocol for ex vivo transduction of HSC with the retroviral vector delineated below could be applied to other monogenic disorders.
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