A Clinically Relevant Mouse Model of Reduced-Intensity Conditioning for Allogeneic HLA-Identical Hematopoietic Stem Cell Transplantation.

Abstract

Allogeneic hematopoietic stem cell transplantation (HCT) is curative for many blood malignancies. This procedure balances the need for engraftment of donor cells while enhancing the curative graft-versus-tumor response. The need to diminish morbidity associated with HCT protocols has led to the development of reduced-intensity conditioning protocols. Modeling the clinical scenario that patients undergo in preclinical small animal models is challenging. We describe herein a mouse model using a conditioning regimen consisting of cytotoxic drugs similar to some human protocols together with reduced-intensity radiation. Furthermore, the choice of a major histocompatibility-matched, minor histocompatibility-mismatched C57BL/6 (H-2) donor to BALB.b (H-2) recipient strain combination resembles the allogeneic human leukocyte antigen-identical sibling or matched unrelated human transplant setting.