Principles of Peripheral Blood Mononuclear Cell Apheresis in a Preclinical Canine Model of Hematopoietic Cell Transplantation

Abstract

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.

Man's best friend: what can pet dogs teach us about non‐Hodgkin's lymphoma?

“…In more recent years, as veterinary care has become more sophisticated and cell separator machines have become available for clinical veterinary use, both autologous and allogeneic BMT are now options to treat CL. A variety of cell separator machines are able to harvest adequate numbers of canine peripheral blood CD34 + cells for BMT , and dogs with CL will undergo complete hematologic reconstitution after otherwise lethal myeloablative therapy if given an appropriate dose of these cells . Lupu et al .…”

“…Lupu et al . described allogeneic BMT to treat a dog with relapsed T‐cell CL that survived >19 months after diagnosis. Our group treated 24 dogs with B‐cell CL using autologous BMT and reported a median disease‐free interval (DFI) and overall survival (OS) of all dogs from the time of BMT as 271 and 463 days, respectively.…”

Collection of Peripheral Blood CD34+ Progenitor Cells from Healthy Dogs and Dogs Diagnosed with Lymphoproliferative Diseases Using a Baxter‐Fenwal CS‐3000 Plus Blood Cell Separator

“…Although PBMC apheresis and plateletpheresis have been reported in dogs using a CaridianBCT machine, the use of a Baxter‐Fenwal CS‐3000 Plus cell separator for apheresis in dogs has not, to the author's knowledge, been reported. The purpose of this study was to determine if the CS‐3000 Plus SVSCH and SVCC can be safely utilized to collect an adequate number of peripheral blood CD34+ mononuclear progenitor cells from dogs weighing <50 kg for HCT after bone marrow ablation.…”

Development of a Minor Histocompatibility Antigen Vaccine Regimen in the Canine Model of Hematopoietic Cell Transplantation

“…Female donor dogs underwent general anesthesia, central venous catheter placement in the external jugular vein, and collection of 200 mL leukapheresis product, as described (COBE 2997; Blood Component Technology, Lakewood, CO) (31,32). Cell counts with differentials were obtained using an ADVIA 2120i (Siemens, Deerfield, IL).…”