• 1

    Burnett RC, Vernau W, Modiano JF, et al. Diagnosis of canine lymphoid neoplasia using clonal rearrangements of antigen receptor genes. Vet Pathol 2003; 40: 3241.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 2

    Vonderhaar MA, Morrison WB. Lymphosarcoma. In: Cancer in dogs and cats: medical and surgical management. Baltimore: The Williams & Wilkins Co, 1998; 667695.

    • Search Google Scholar
    • Export Citation
  • 3

    Kitchell BE, Dhaliwal RS. Section 6. Hematology, oncology and immunology. CVT update: anti cancer drugs and protocols using traditional drugs. In: Bonagura JD, ed. Kirk's current veterinary therapy XIII: small animal practice. Philadelphia: WB Saunders Co, 1995; 465473.

    • Search Google Scholar
    • Export Citation
  • 4

    Wagner JL, Burnett RC, Works JD, et al. Molecular analysis of DLA-DRBB1 polymorphism. Tissue Antigens 1996; 48: 554561.

  • 5

    Wagner JL, Burnett RC, DeRose SA, et al. Histocompatibility testing of dog families with highly polymorphic microsatellite markers. Transplantation 1996; 62: 876877.

    • Search Google Scholar
    • Export Citation
  • 6

    Burnett RC, Francisco LV, DeRose SA, et al. Identification and characterization of a highly polymorphic microsatellite marker within the canine MHC class I region. Mamm Genome 1995; 6: 684685.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 7

    Mellersh CS, Langston AA, Acland GM, et al. A linkage map of the canine genome. Genomics 1997; 46: 326336.

  • 8

    Francisco LV, Langston AA, Mellersh CS, et al. A class of highly polymorphic tetranucleotide repeats for canine genetic mapping. Mamm Genome 1996; 7: 359362.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9

    Kennedy LJ, Carter SD, Barnes A, et al. Interbreed variation of DLA-DRB1, DQA1 alleles and haplotypes in the dog. Vet Immunol Immunopathol 1999; 69: 101111.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 10

    Wagner JL, Creer SA, Storb R. Dog class I gene DLA-88 histocompatibility typing by PCR-SSCP and sequencing (brief communication). Tissue Antigens 2000; 55: 564567.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 11

    Wagner JL, Works JD, Storb R. DLA-DRB1 and DLA-DQB1 histocompatibility typing by PCR-SSCP and sequencing (brief communication). Tissue Antigens 1998; 52: 397401.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 12

    Lee R, Storb R, Little M-T, et al. Percutaneous central duallumen catheter for apheresis in the canine. J Invest Surg 2002; 15: 337341.

  • 13

    McSweeney PA, Rouleau KA, Wallace PM, et al. Characterization of monoclonal antibodies that recognize canine CD34. Blood 1998; 91: 19771986.

  • 14

    Yu C, Ostrander E, Bryant E, et al. Use of (CA)n polymorphisms to determine the origin of blood cells after allogeneic canine marrow grafting. Transplantation 1994; 58: 701706.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 15

    von Euler H, Einarsson R, Olsson U, et al. Serum thymidine kinase activity in dogs with malignant lymphoma: a potent marker for prognosis and monitoring the disease. J Vet Intern Med 2004; 18: 696702.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 16

    Kraegel SA. Appendices, appendix A: cancer-lymphoma. In: Ettinger SJ, Feldman EC, eds. Textbook of veterinary internal medicine: diseases of the dog and cat. Vol. 2. 5th ed. Philadelphia: WB Saunders Co, 2000; 1923.

    • Search Google Scholar
    • Export Citation
  • 17

    Deeg HJ, Storb R. Bone marrow transplantation in dogs. In: Makowka L, Cramer DV, Podesta LG, eds. Handbook of animal models in transplantation research. Boca Raton, Fla: CRC Press Inc, 1994; 255285.

    • Search Google Scholar
    • Export Citation
  • 18

    Wagner JL, Storb R. Preclinical large animal models for hematopoietic stem cell transplantation. Curr Opin Hematol 1996; 3: 410415.

  • 19

    Thomas ED, Storb R. The development of the scientific foundation of hematopoietic cell transplantation based on animal and human studies. In: Thomas ED, Blume KG, Forman SJ, eds. Hematopoietic cell transplantation. 2nd Ed. Boston: Blackwell Science, 1999; 111.

    • Search Google Scholar
    • Export Citation
  • 20

    Vriesendorp HM, Westbroek DL, D'Amaro J, et al. Joint report of 1st International Workshop on Canine Immunogenetics. Tissue Antigens 1973; 3: 145163.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 21

    Sarmiento UM, Storb RF. Characterization of class II alpha genes and DLA-D region allelic associations in the dog. Tissue Antigens 1988; 32: 224234.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 22

    Burnett RC, DeRose SA, Wagner JL, et al. Molecular analysis of six dog leukocyte antigen class I sequences including three complete genes, two truncated genes, and one full-length processed gene. Tissue Antigens 1997; 49: 484495.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 23

    Graumann MB, DeRose SA, Ostrander EA, et al. Polymorphism analysis of four canine MHC class I genes. Tissue Antigens 1998; 51: 374381.

  • 24

    Weiden PL, Storb R, Lerner KG, et al. Treatment of canine malignancies by 1200 R total body irradiation and autologous marrow grafts. Exp Hematol 1975; 3: 124134.

    • Search Google Scholar
    • Export Citation
  • 25

    Weiden PL, Storb R, Shulman H, et al. Dimethyl myleran and autologous marrow grafting for the treatment of spontaneous canine lymphoma. Eur J Cancer Clin Oncol 1977; 13: 14111415.

    • Search Google Scholar
    • Export Citation
  • 26

    Weiden PL, Storb R, Deeg HJ, et al. Prolonged disease-free survival in dogs with lymphoma after total-body irradiation and autologous marrow transplantation consolidation of combinationchemotherapy-induced remissions. Blood 1979; 54: 10391049.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 27

    Weiden PL, Storb R, Deeg HJ, et al. Total body irradiation and autologous marrow transplantation as consolidation therapy for spontaneous canine lymphoma in remission. Exp Hematol 1979; 7(suppl5): 160163.

    • Search Google Scholar
    • Export Citation
  • 28

    Deeg HJ, Appelbaum FR, Weiden PL, et al. Autologous marrow transplantation as consolidation therapy for canine lymphoma: efficacy and toxicity of various regimens of total body irradiation. Am J Vet Res 1985; 46: 20162018.

    • Search Google Scholar
    • Export Citation
  • 29

    Appelbaum FR, Deeg HJ, Storb R, et al. Cure of malignant lymphoma in dogs with peripheral blood stem cell transplantation. Transplantation 1986; 42: 1922.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 30

    Appelbaum FR, Deeg HJ, Storb R, et al. Marrow transplant studies in dogs with malignant lymphoma. Transplantation 1985; 39: 499504.

  • 31

    Epstein RB, Graham TC, Storb R, et al. Studies of marrow transplantation, chemotherapy and cross-circulation in canine lymphosarcoma. Blood 1971; 37: 349359.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 32

    Weiden PL, Storb R, Sale GE, et al. Allogeneic hematopoietic grafts after total-body irradiation in dogs with spontaneous tumors. J Natl Cancer Inst 1978; 61: 353357.

    • Search Google Scholar
    • Export Citation
  • 33

    Weiden PL, Storb R, Deeg HJ. Antitumor effect of marrow transplantation in randomly bred species: studies in dogs with spontaneous lymphoma. In: Okunewick J, Meredith R, eds. Graft-versusleukemia in man and animal models. Boca Raton, Fla: CRC Press Inc, 1981; 127138.

    • Search Google Scholar
    • Export Citation
  • 34

    Storb R, Thomas ED. Graft-versus-host disease in dog and man: the Seattle experience (review). Immunol Rev 1985; 88: 215238.

  • 35

    Storb R, Yu C, Wagner JL, et al. Stable mixed hematopoietic chimerism in DLA-identical littermate dogs given sublethal total body irradiation before and pharmacological immunosuppression after marrow transplantation. Blood 1997; 89: 30483054.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 36

    Sandmaier BM, Storb R, Santos EB, et al. Allogeneic transplants of canine peripheral blood stem cells mobilized by recombinant canine hematopoietic growth factors. Blood 1996; 87: 35083513.

    • Crossref
    • Search Google Scholar
    • Export Citation

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Use of multigeneration-family molecular dog leukocyte antigen typing to select a hematopoietic cell transplant donor for a dog with T-cell lymphoma

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  • 1 Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, Seattle, WA 98109.
  • | 2 Bellingham Veterinary & Critical Care, 720 Virginia St, Bellingham, WA 98225.
  • | 3 Bellingham Veterinary & Critical Care, 720 Virginia St, Bellingham, WA 98225.
  • | 4 Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, Seattle, WA 98109.
  • | 5 Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, Seattle, WA 98109.
  • | 6 Department of Comparative Medicine, School of Medicine, University of Washington, Seattle, WA 98195.
  • | 7 Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, Davis, CA 95616.
  • | 8 Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, Seattle, WA 98109.
  • | 9 Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, Seattle, WA 98109.
  • | 10 Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, Seattle, WA 98109.
  • | 11 Department of Surgery, School of Medicine, University of Washington, Seattle, WA 98195.
  • | 12 Department of Urology, School of Medicine, University of Washington, Seattle, WA 98195.
  • | 13 Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, Seattle, WA 98109.
  • | 14 Department of Medicine, School of Medicine, University of Washington, Seattle, WA 98195.

Abstract

Case Description—A 7-year-old Golden Retriever was examined because of anorexia, lethargy, vomiting, and gradual weight loss.

Clinical Findings—Splenomegaly, pancytopenia, high serum calcium concentration, and high alkaline phosphatase activity were detected. Magnetic resonance imaging revealed an enlarged mesenteric lymph node and increased signals from the bone marrow of the ilium and vertebral bodies. Histologic examination and immunophenotyping of biopsy specimens confirmed a stage V (b) T-cell malignant lymphoma.

Treatment and Outcome—Clinical remission was attained by use of 2 chemotherapy cycles, followed by an allogeneic hematopoietic cell transplant performed at 18 weeks after diagnosis. A donor was identified by molecular dog leukocyte antigen typing methods. The patient was conditioned with 2 fractions of 4 Gy total body irradiation delivered 3 hours apart at 7 cGy/min, followed by an IV infusion of recombinant canine granulocyte colony-stimulating factor mobilized leukapheresis product and postgrafting immunosuppression with cyclosporine. Chimerism analyses revealed full donor engraftment that has been maintained for at least 58 weeks after transplant. Remission has been confirmed by normal results of serum thymidine kinase assays and the absence of peripheral blood clonal T-cell receptor gene rearrangements.

Clinical Relevance—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.

Abstract

Case Description—A 7-year-old Golden Retriever was examined because of anorexia, lethargy, vomiting, and gradual weight loss.

Clinical Findings—Splenomegaly, pancytopenia, high serum calcium concentration, and high alkaline phosphatase activity were detected. Magnetic resonance imaging revealed an enlarged mesenteric lymph node and increased signals from the bone marrow of the ilium and vertebral bodies. Histologic examination and immunophenotyping of biopsy specimens confirmed a stage V (b) T-cell malignant lymphoma.

Treatment and Outcome—Clinical remission was attained by use of 2 chemotherapy cycles, followed by an allogeneic hematopoietic cell transplant performed at 18 weeks after diagnosis. A donor was identified by molecular dog leukocyte antigen typing methods. The patient was conditioned with 2 fractions of 4 Gy total body irradiation delivered 3 hours apart at 7 cGy/min, followed by an IV infusion of recombinant canine granulocyte colony-stimulating factor mobilized leukapheresis product and postgrafting immunosuppression with cyclosporine. Chimerism analyses revealed full donor engraftment that has been maintained for at least 58 weeks after transplant. Remission has been confirmed by normal results of serum thymidine kinase assays and the absence of peripheral blood clonal T-cell receptor gene rearrangements.

Clinical Relevance—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.

Contributor Notes

Dr. Lupu is the recipient of a fellowship in Oncology and Transplantation Biology from the National Institutes of Health, Bethesda, Md.

The authors thank Sue Hendrickson for coordination of blood sample collection from the patient's family members and Drs. George Sale and David Myerson for histologic review of the biopsy specimens.

Dr. Storb at Fred Hutchinson Cancer Research Center.