Development of retroviral vectors that target hematopoietic stem cells

I. INTRODUCTION Allografting is a well-documented curative therapy for patients with leukemias and other hematological malignancies. Conventional myeloablative regimens for allografting usually involve high-dose chemotherapy alone or in combination with total body irradiation. Such regimens have been considered to be essential for allografting, because they do eliminate from the marrow the host hematopoietic progenitor cells (HPCs) (and therefore they make “space” for the donor HPCs), avoid rejection of these cells, and drastically reduce or eliminate the neoplastic cells of the host (1,2). Recently, it has been demonstrated that the mechanism of tumor cell control is due to the alloreactivity of donor immune cells, and therefore adoptive allogeneic therapy plays a fundamental role mainly in chronic myelogenous leukemia (3), but also in other hematological neoplasias (4). Considering that it is now possible to eradicate high tumor burdens by adoptive allogeneic therapy through donor lymphocyte infusion (DLI) in patients relapsing after high-dose myeloablative approaches, the crucial question is: Is the myeloablation still essential considering that the induction of host-versus-graft tolerance is usually accomplished by successful stable donor cell engraftment?.