Background: Preclinical studies of peripheral blood mononuclear cell (PBMC) transplantation conducted in a well-established canine hematopoietic cell transplantation (HCT) model have been successfully translated to human patients over the past 5 decades.Objective: We retrospectively investigated the safety and feasibility of PBMC apheresis in the canine model of HCT by analyzing apheresis parameters, cell yields, and the impacts of donor-related and apheresis-related variables on collection yields and donor stability.Animals: One hundred and twenty dogs that underwent PBMC aphereses were evaluated. Methods: Aphereses were performed with a COBE Spectra blood separator and a central dual-lumen catheter, with or without recombinant canine granulocyte colony-stimulating factor (rcG-CSF) stem cell mobilization.Results: Aphereses from dogs not given rcG-CSF yielded an average volume of 280 AE 42 mL containing an average of 15,086 AE 9,834 leukocytes/mL. Aphereses from dogs given rcG-CSF yielded an average volume of 261 AE 55 mL containing an average of 39,711 AE 24,488 leukocytes/mL. Higher pre-apheresis white blood cell (WBC) counts correlated with higher apheresis WBC yields (R 5 0.50, Po.0001). The correlations of collection time, inlet volume, and collection flow rate on WBC yields were statistically significant but only weak to moderate in magnitude (R 5 0.34, P 5 .0001; R 5 0.38, P 5 .0006; R 5 0.26, P 5 .002, respectively) as were the correlations of collection time and inlet volume on collection volumes (R 5 0.30, P 5 .002; R 5 0.42, Po.0001, respectively). All dogs recovered promptly after PBMC aphereses and catheter removal, without complications.Conclusions and Clinical Importance: These data may be useful for translating PBMC apheresis technology to the field of veterinary oncology for the treatment of dogs with hematologic malignancies.
Systemic chemotherapy induces remissions; however, most dogs succumb to disease recurrence because of multidrug resistance. Outcome of allogeneic hematopoietic cell transplantation in dogs can be excellent because of improved donor-recipient selection by use of molecular dog leukocyte antigen typing, compared with early attempts, and better prevention of graft versus host disease, better supportive care, and substitution of peripheral blood mononuclear cells for bone marrow.
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 effi cacy 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 benefi t 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.
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