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Multi-generation family molecular dog leukocyte antigen (DLA) typing to select a hematopoietic cell transplant donor for the treatment of a dog with spontaneous T-cell lymphoma – Oral presentation

Domenii publicaţii > Ştiinţe medicale + Tipuri publicaţii > Articol în volumul unei conferinţe

Autori: Lupu M., Sullivan E., Westfall T., Weigler B., Stroup P., Zellmer E., Kuhr C.S., Storb R

Editorial: Proceedings, The 30th Congress of the World Small Animal Veterinary Association, Mexico City, Mexico, May 11-14, 2005.

Rezumat:

Canine lymphoma is incurable by chemotherapy alone. However, cures are possible with allogeneic hematopoietic cell transplantation if a suitable DLA matched donor can be identified.

Here, a 7-year-old male Golden Retriever with spontaneous T-cell lymphoma was induced into clinical remission by two chemotherapy cycles. Twenty-eight members of the dog’s pedigree from 5 generations and located in 3 countries were identified. Their blood samples and that of the lymphoma dog were tested for highly polymorphic microsatellite markers within the DLA class I (FH 2200) and DLA class II (FH 2202) regions. Segregation analysis of the polymorphisms suggested that 5 family members were DLA matched with the lymphoma dog. This was confirmed by DNA sequencing of DLA-DRB1 alleles. A 13-month-old male donor was chosen, one of his littermate’s descendents, from the fourth generation pedigree level. The lymphoma dog was conditioned with two 4 Gy fractions of total body irradiation, delivered 3 hours apart at 7 cGy/min from a 4 MEV linear accelerator, followed by canine G-CSF mobilized peripheral blood mononuclear cells from the donor (3.6 x 10< sup >6< /sup > CD34+ cells/kg) and post-grafting immunosuppression with cyclosporine, 5 mg/kg b.i.d. orally, administered from day-1 to day 35 after transplant. Following the post-irradiation nadir, neutrophil counts normalized by day 10, platelet counts by day 22, and the dog didn’t require any blood transfusion support. Chimerism analyses for both granulocyte and lymphocyte fractions showed full donor engraftment as early as 2 weeks after transplant. On day 68 after the transplant, the dog developed graft-vs.-host disease skin lesions, which responded to resumption of cyclosporine therapy.

The dog is now surviving with high quality of life more than 148 days after transplant with complete donor engraftment, controlled graft-vs.-host disease, and no evidence of residual tumor.

Abstract available at: http://www.vin.com/proceedings/Proceedings.plx?CID=WSAVA2005&Author=7068&O=Generic
Accessed March 5, 2007.

Cuvinte cheie: transplant de celule stem hematopoietice, typizare moleculara a complexului major de histocompatibilitate canin, limfom malign, caine // hematopoietic cell transplantation, molecular dog leukocyte antigen typing, malignant lymphoma, dog