Background Peripheral blood CD34+ hematopoietic cell transplantation (PBHCT) is commonly used to treat human patients with relapsed non-Hodgkin diffuse, large B-cell lymphoma with cure rates approaching 50%. Objective To determine the safety and feasibility of performing PBHCT to treat canine B-cell lymphoma (LSA) patients in a clinical academic setting. Animals Twenty-four client-owned dogs diagnosed with B-cell LSA. Methods After high-dose cyclophosphamide and rhG-colony-stimulating factor treatment, peripheral blood mononuclear cells were collected using cell separator machines. The harvested cells then were infused after a 10 Gy dose of total body irradiation (TBI). Post-irradiation adverse effects were managed symptomatically and dogs were discharged upon evidence of engraftment. Results More than 2 × 106 CD34+ cells/kg were harvested in 23/24 dogs. Preapheresis peripheral blood monocyte count was correlated with the number of CD34+ cells/kg harvested. Twenty-one of 24 (87.5%) dogs engrafted appropriately, whereas 2 dogs (8.3%) died in the hospital. One (5%) dog exhibited delayed engraftment and died 45 days after PBHCT. One dog developed presumed TBI-induced pulmonary fibrosis approximately 8 months after PBHCT. The median disease-free interval and overall survival (OS) of all dogs from the time of PBHCT was 271 and 463 days, respectively. Five of 15 (33%) dogs transplanted before they relapsed remain in clinical remission for their disease at a median OS of 524 days (range, 361–665 days). Conclusions and Clinical Importance In most cases, PBHCT led to complete hematologic reconstitution. Therefore, PBHCT may be considered as a treatment option for dogs with B-cell lymphoma.
FMS-like tyrosine kinase 3 (FLT3) is a commonly mutated protein in a variety of human acute leukemias. Mutations leading to constitutively active FLT3, including internal tandem duplications of the juxtamembrane domain (ITD), result in continuous cellular proliferation, resistance to apoptotic cell death, and a poorer prognosis. A better understanding of the molecular consequences of FLT3 activation would allow improved therapeutic strategies in these patients. Canine lymphoproliferative diseases, including lymphoma and acute leukemias, share evolutionarily conserved chromosomal aberrations and exhibit conserved mutations within key oncogenes when compared to their human counterparts. A small percentage of canine acute lymphocytic leukemias (ALL) also exhibit FLT3 ITD mutations.
23 November 2011 in Veterinary and Comparative Oncology
Background: Peripheral blood hematopoietic cell transplantation (PBHCT) is a feasible treatment option for dogs with B-cell lymphoma. Objective: To examine apheresis and PBHCT outcomes in dogs diagnosed with T-cell lymphoma (TCL). Animals: Fifteen client-owned dogs diagnosed with high-grade TCL. Methods: After high-dose cyclophosphamide and rhG-colony-stimulating (rhG-CSF) factor treatment, peripheral blood mononuclear cells were collected using cell separators. The harvested cells then were infused after varying doses of total body irradiation (TBI). Postirradiation adverse effects were managed symptomatically and dogs were discharged upon evidence of hematopoietic engraftment. Results: More than 2 × 106 CD34+ cells/kg were harvested from 15/15 dogs. Thirteen of 15 (87%) dogs engrafted appropriately, whereas 2 (13%) of the dogs died in the hospital. One dog developed cutaneous B-cell lymphoma 120 days post-PBHCT. The median disease-free interval and overall survival (OS) of the 13 dogs transplanted in first remission from the time of PBHCT were 184 and 240 days, respectively. Stage and substage of disease at diagnosis had no effect on OS. Two of 13 (15%) dogs were alive 741 and 772 days post-PBHCT. Conclusions and Clinical Importance: PBHCT may be considered as a treatment option for dogs with TCL.