Ballen Karen K, Spitzer Thomas R, Yeap Beow Y, McAfee Steven, Dey Bimalangshu R, Attar Eyal, Haspel Richard, Kao Grace, Liney Deborah, Alyea Edwin, Lee Stephanie, Cutler Corey, Ho Vincent, Soiffer Robert, Antin Joseph H
Division of Hematology/Oncology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
Biol Blood Marrow Transplant. 2007 Jan;13(1):82-9. doi: 10.1016/j.bbmt.2006.08.041.
Umbilical cord blood (UBC) stem cells are a useful stem cell source for patients without matched related or unrelated donors. Adult transplantation with single UBC units is associated with high transplantation-related mortality (TRM). In most cases, mortality is due to infection related to slow engraftment and immunoincompetence. In this study, we used a reduced-intensity conditioning regimen of fludarabine, melphalan, and antithymocyte globulin followed by 2 partially matched UBC units. The UBC units were a 4/6 HLA match or better with each other and with the patient and achieved a minimum precryopreservation cell dose of 3.7 x 10(7) nucleated cells/kg. A total of 21 patients (median age, 49 years) were treated. The median time to an absolute neutrophil count > 0.5 x 10(9)/L was 20 days, and the median time to an unsupported platelet count > 20 x 10(9)/L was 41 days. Two patients experienced primary graft failure and underwent a second UBC transplantation. One patient had a late graft failure. Acute graft-versus-host disease (GVHD) grade II-IV occurred in 40% of patients. The 100-day TRM was 14%, and the 1-year disease-free survival was 67%. Mixed chimerism was associated with a higher risk of chronic GVHD. Our findings indicate that adult patients can tolerate double UBC transplantation well and achieve sustained antitumor responses using this reduced-intensity conditioning regimen.
脐带血（UBC）干细胞对于没有匹配的相关或无关供体的患者来说是一种有用的干细胞来源。单单位UBC用于成人移植时，与高移植相关死亡率（TRM）相关。在大多数情况下，死亡是由于与植入缓慢和免疫无反应相关的感染。在本研究中，我们采用了氟达拉滨、美法仑和抗胸腺细胞球蛋白的减低强度预处理方案，随后移植2个部分匹配的UBC单位。这些UBC单位彼此之间以及与患者的人类白细胞抗原（HLA）匹配度为4/6或更高，并且在冷冻保存前的有核细胞最低剂量达到3.7×10⁷个有核细胞/千克。共有21例患者（中位年龄49岁）接受了治疗。绝对中性粒细胞计数>0.5×10⁹/L的中位时间为20天，血小板计数>20×10⁹/L且无需支持的中位时间为41天。2例患者发生原发性移植物失败并接受了第二次UBC移植。1例患者发生迟发性移植物失败。40%的患者发生了II-IV级急性移植物抗宿主病（GVHD）。100天TRM为14%，1年无病生存率为67%。混合嵌合与慢性GVHD的较高风险相关。我们的研究结果表明，成年患者能够很好地耐受双UBC移植，并使用这种减低强度预处理方案实现持续的抗肿瘤反应。
