Lupu Marilena, Sullivan Edmund W, Westfall Theresa E, Little Marie-Térèse, Weigler Benjamin J, Moore Peter F, Stroup Patrice A, Zellmer Eustacia, Kuhr Christian, Storb Rainer
Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, Seattle, WA 98109, USA.
J Am Vet Med Assoc. 2006 Mar 1;228(5):728-32. doi: 10.2460/javma.228.5.728.
A 7-year-old Golden Retriever was examined because of anorexia, lethargy, vomiting, and gradual weight loss.
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.
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.
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.
一只7岁的金毛猎犬因厌食、嗜睡、呕吐和体重逐渐减轻而接受检查。
检测到脾肿大、全血细胞减少、血清钙浓度升高和碱性磷酸酶活性升高。磁共振成像显示肠系膜淋巴结肿大，髂骨和椎体骨髓信号增强。活检标本的组织学检查和免疫表型分析证实为V（b）期T细胞恶性淋巴瘤。
通过2个化疗周期实现临床缓解，随后在诊断后18周进行异基因造血细胞移植。通过分子犬白细胞抗原分型方法确定了供体。患者接受了2次全身照射，每次4 Gy，间隔3小时，以7 cGy/分钟的速度进行，随后静脉输注重组犬粒细胞集落刺激因子动员的白细胞分离产物，并使用环孢素进行移植后免疫抑制。嵌合体分析显示完全供体植入，移植后至少维持了58周。血清胸苷激酶检测结果正常且外周血克隆性T细胞受体基因重排阴性证实了缓解。
全身化疗可诱导缓解；然而，大多数犬因多药耐药而死于疾病复发。与早期尝试相比，通过使用分子犬白细胞抗原分型改善供体-受体选择、更好地预防移植物抗宿主病、更好的支持治疗以及用外周血单个核细胞替代骨髓，犬异基因造血细胞移植的结果可能非常好。
