Opening Marrow Niches in Patients Undergoing Autologous Hematopoietic Stem Cell Gene Therapy.

Successful gene therapy for genetic disorders requires marrow niches to be opened to varying degrees to engraft gene-corrected hematopoietic stem cells (HSC). For example, in severe combined immunodeficiency, relatively limited chimerism is necessary for both T- and B-cell immune reconstitution, whereas for inborn errors of metabolism maximal donor chimerism is the goal. Currently, alkylating chemotherapy is used for this purpose. Significant pharmacokinetic variability exists in drug clearance in children less than 12 years old. Thus, pharmacokinetic monitoring is needed to achieve the targeted exposure goal for busulfan.