Five decades of progress in haematopoietic cell transplantation based on the preclinical canine model

Abstract

The preclinical canine model has proved valuable for the development of principles and techniques of haematopoietic cell transplantation (HCT) applicable to human patients. Studies in random-bred dogs concerning the impact of histocompatibility barriers on engraftment and graft-versus-host disease, the kinetics of immunological reconstitution, the efficacy of various pretransplant conditioning regimens, post-transplantation immunosuppression protocols, treatment of malignant diseases, and graft-versus-tumour effects have advanced HCT from an investigational therapy with uncertain clinical benefit half a century ago to an important treatment choice for thousands of patients treated annually in transplantation centres worldwide. More recent preclinical canine studies have resulted in the clinical translation of non-myeloablative, minimally invasive transplantation protocols that have extended allogeneic HCT to include older human patients with malignant and non-malignant, acquired or inherited haematological disorders, and those with comorbid conditions. Here, we review the contributions of the canine model to modern HCT and describe the usefulness of HCT for the treatment of canine haematological disorders.