Abstract
Hematopoietic stem cell transplantation (HSCT) has been established as an effective therapy for selected inborn errors of metabolism. The success of HSCT in metabolic disease is best exemplified through the treatment of Hurler's syndrome, a lysosomal storage disease. Through the collaborative effort of several international centers, factors that predict successful patient and transplant outcomes have been identified. In this review, we discuss the principles that underlie the use of HSCT in metabolic diseases. We consider the clinical indications, conditioning regimens, and disease-specific follow-up for HSCT in different metabolic diseases. We highlight persisting challenges in HSCT to delay progression of certain organ systems that remain refractory to HSCT and the relatively high rates of aplastic graft failure. Finally, we evaluate the variable applicability of these principles to other inherited metabolic disorders including peroxisomal, mitochondrial, and other lysosomal storage diseases.
Highlights
Inherited metabolic disorders comprise a large, diverse, and complex group of diseases caused by defects in genes that code for proteins involved in metabolic pathways
Autologous HSCT using gene therapy may facilitate supranormal enzyme production by transducing a patient’s HSCs with a viral vector ex vivo, and infusing them back into the patient following appropriate conditioning. These gene-corrected cells can integrate into the host genome, where certain viral vectors such as lentiviruses can do so with a lower risk of insertional mutagenesis
ET and RW were the main authors with contributions by JB and SJ
Summary
Tan 1, Jaap Jan Boelens 2, Simon A. Wynn 3* on behalf of the Inborn Errors Working Party of the EBMT. Hematopoietic stem cell transplantation (HSCT) has been established as an effective therapy for selected inborn errors of metabolism. The success of HSCT in metabolic disease is best exemplified through the treatment of Hurler’s syndrome, a lysosomal storage disease. Through the collaborative effort of several international centers, factors that predict successful patient and transplant outcomes have been identified. We discuss the principles that underlie the use of HSCT in metabolic diseases. We consider the clinical indications, conditioning regimens, and disease-specific follow-up for HSCT in different metabolic diseases. We evaluate the variable applicability of these principles to other inherited metabolic disorders including peroxisomal, mitochondrial, and other lysosomal storage diseases
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