Clinical Research Division, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, Washington 98109, USA.
Biol Blood Marrow Transplant. 2010 Aug;16(8):1090-8. doi: 10.1016/j.bbmt.2010.03.010. Epub 2010 Mar 18.
Cord blood transplantation (CBT) with units containing total nucleated cell (TNC) dose >2.5 x 10(7)/kg is associated with improved engraftment and decreased transplant-related mortality. For many adults no single cord blood units are available that meet the cell dose requirements. We developed a dog model of CBT to evaluate approaches to overcome the problem of low cell dose cord blood units. This study primarily compared double- versus single-unit CBT. Unrelated dogs were bred and cord blood units were harvested. We identified unrelated recipients that were dog leukocyte antigen (DLA)-88 (class I) and DLA-DRB1 (class II) allele-matched with cryopreserved units. Each unit contained <or=1.7 x 10(7) TNC/kg. Recipients were given 9.2 Gy total-body irradiation (TBI) and DLA-matched unrelated cord blood with postgrafting cyclosporine and mycophenolate mofetil. After double-unit CBT, 5 dogs engrafted and 4 survived long term with 1 dominant engrafting unit and prompt immune reconstitution. In contrast, 0 of 5 dogs given single-unit CBT survived beyond 105 days (P = .03, log-rank test); neutrophil and platelet recovery was delayed (both P = .005) and recipients developed fatal infections. This new large animal model showed that outcomes were improved after double-unit compared to single-unit CBT. After double-unit CBT, the nonengrafted unit facilitates engraftment of the dominant unit.
脐带血移植（CBT）中，使用含有>2.5×10(7)/kg 总核细胞（TNC）剂量的单位与改善植入和降低移植相关死亡率相关。对于许多成年人来说，没有符合细胞剂量要求的单个脐带血单位。我们开发了一种 CBT 的犬模型，以评估克服低细胞剂量脐带血单位问题的方法。本研究主要比较了双单位与单单位 CBT。无关的犬被繁殖，采集脐带血单位。我们确定了与冷冻单位 HLA 88（I 类）和 HLA-DRB1（II 类）等位基因匹配的无关受者。每个单位含有<或=1.7×10(7)TNC/kg。受者接受 9.2Gy 全身照射（TBI）和与移植后环孢菌素和霉酚酸酯联合使用的 HLA 匹配的无关脐带血。在双单位 CBT 后，5 只犬植入，4 只长期存活，1 只主要植入单位，免疫重建迅速。相比之下，接受单单位 CBT 的 5 只犬中没有 1 只存活超过 105 天（P=0.03，对数秩检验）；中性粒细胞和血小板恢复延迟（均 P=0.005），受者发生致命感染。这种新的大动物模型表明，与单单位 CBT 相比，双单位 CBT 后结果得到改善。在双单位 CBT 后，未植入的单位促进了主导单位的植入。
