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156 Apheresis in Companion Animals 1371
combination of plasmapheresis and immunoabsorption. amount of hematopoietic progenitor cells for use in the
VetBooks.ir Plasmapheresis was performed eight times over a period canine bone marrow transplant setting.
of 45 days using the same cell separator and the har-
vested product was then passed over a column loaded
with Staphylococcus purified protein A/SSPA, which Leukapheresis Followed by Bone Marrow
Transplantation
binds canine IgG classes of antibodies. This dog also
responded well clinically. Based on this case report, Early research, performed mainly at the Fred Hutchinson
Matus et al. then treated five dogs with systemic lupus Research Center, proved that canine peripheral blood
and two dogs with immune‐mediated hemolytic anemia CD34+ progenitor cells harvested using human cell sep-
using plasmapheresis alone, using the same IBM cell arators could lead to complete hematologic reconstitu-
separator. One total plasma volume was removed and tion following lethal myeloablative therapy. Further work
replaced with LRS and all dogs responded clinically showed that dogs with lymphoma could be successfully
within 24 hourrs of the procedure. treated in both an autologous and allogeneic bone mar-
Dogs have been undergoing leukapheresis in a research row transplant setting with long‐term survivals longer
setting since 1967, although the collection of large than chemotherapy alone.
amounts of cells needed for routine clinical use using More recently, our group at North Carolina State
CFC was not possible until the cloning and large‐scale University used a combination of total body irradiation
production of recombinant hematopoietic cytokines in and autologous peripheral blood CD34+ progenitor
the 1990s and the development of highly automated cells, harvested using either a CS‐3000 Plus or COBE
computer‐controlled cell separators soon thereafter. Spectra cell separator, to treat dogs with high‐grade B
Although there is a large body of research literature and T cell lymphoma. Five of 15 (33%) dogs with B cell
utilizing dogs as a preclinical model to develop leuka- lymphoma transplanted while in remission for their
pheresis techniques to collect a sufficient number of disease remained alive >2 years (median overall survival
peripheral blood CD34+ cells to allow complete hemato- 524 days), while two of 13 (15%) dogs with T cell lym-
logic reconstitution following myeloablative therapy, the phoma transplanted while in remission for their disease
use of leukapheresis in the veterinary clinical setting is remained alive >2 years (median overall survival 240
still in its infancy. days). Importantly, when we transplanted dogs with B
In 2006, Lupu et al. reported the use of a COBE Spectra cell lymphoma who were not in clinical remission, their
cell separator to harvest enough peripheral blood CD34+ median disease‐free intervals were significantly shorter
6
progenitor cells (>5 × 10 /kg) for use in an allogeneic than those who were in remission (52 days vs 456 days).
bone marrow transplant setting. Their choice of cell sep- In dogs with T cell lymphoma, although a smaller per-
arator was based on the experience of the group at the centage of dogs were alive >2 years compared with
Fred Hutchinson Cancer Research Center which showed the B cell lymphoma dogs, the median overall survival
that automated apheresis using a COBE Spectra machine from the time of diagnosis to death was 602 days (range
developed for humans could also be used in dogs. Our 246–928 days), which is significantly longer than when
group at North Carolina State University also found that dogs are treated with chemotherapy alone.
an adequate number of peripheral blood progenitor cells Our group has also performed two allogeneic bone
could be safely harvested from dogs using a Fresenius marrow transplants using DLA‐matched donor periph-
Kabi CS‐3000 Plus cell separator. We also showed that eral blood CD34+ cells to treat one dog with B cell and
the CD34+ component of the harvest product was ade- one dog with T cell lymphoma (unpublished data). Both
quate to achieve complete hematopoietic reconstitution dogs underwent complete hematologic reconstitution
following lethal total body irradiation. and achieved full donor engraftment within six weeks of
Finally, since all cell separator machines are designed transplant. The dog with B cell lymphoma died of unex-
for adult humans and their use in small children and plained causes ~6 months post transplant, while the dog
dogs can be challenging, our group showed, similar to with T cell lymphoma remains alive ~22 months post
human pediatric data, that apheresis using a COBE transplant. We also treated a dog with acute large granular
Spectra cell separator can be safely performed in dogs lymphocytic leukemia using DLA‐matched donor periph-
weighing <14 kg if appropriate machine priming tech- eral blood CD34+ cells and this dog remains disease free
niques are utilized. The smallest dog on which our group at ~30 months post transplant. Both autologous and allo-
has performed apheresis on weighed 4.6 kg (unpublished geneic bone marrow transplantation as treatments of
data). This combination of older and more recent data canine lymphoproliferative disorders are currently offered
clearly shows that canine leukapheresis is safe in a clini- at North Carolina State University and three private
cal setting and the procedure can harvest an adequate practices in the United States (CA, WA, and OH).