Department of Stem Cell Transplantation and Cellular Therapy, Division of Pathology/Lab Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Department of Laboratory Medicine, Division of Pathology/Lab Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Biol Blood Marrow Transplant. 2017 Aug;23(8):1359-1366. doi: 10.1016/j.bbmt.2017.05.002. Epub 2017 May 12.
We previously showed the safety of using cord blood (CB) expanded ex vivo in cocultures with allogeneic mesenchymal precursor cells (MPC) after myeloablative conditioning with faster recovery of neutrophils and platelets compared with historical controls. Herein, we report the transplantation outcomes of 27 patients with hematologic cancers who received 1 CB unit expanded ex vivo with MPCs in addition to an unmanipulated CB (MPC group) after reduced-intensity conditioning (RIC). The results in this group were compared with 51 historical controls who received 2 unmanipulated CB units (control group). The analyses were stratified for 2 RIC treatment groups: (1) total body irradiation 200 cGy + cyclophosphamide + fludarabine) (TCF), and (2) fludarabine + melphalan (FM). Coculture of CB with MPCs led to an expansion of total nucleated cells by a median factor of 12 and of CD34 cells by a median factor of 49. In patients in whom engraftment occurred, the median time to neutrophil engraftment was 12 days in the MPC group, as compared with 16 days in controls (P = .02). The faster neutrophil engraftment was observed in both RIC groups. The cumulative incidence of neutrophil engraftment on day 26 was 75% with expansion versus 50% without expansion in patients who received FM as the RIC regimen (P = .03). Incidence of neutrophil engraftment was comparable in MPC and control groups if treated with TCF (82% versus 79%, P = .40). Transplantation of CB units expanded with MPCs is safe and effective with faster neutrophil engraftment even after RIC regimens.
我们之前已经证明了在经过清髓性预处理后，使用与异体间充质前体细胞（MPC）共培养体外扩增的脐带血（CB）的安全性，与历史对照相比，中性粒细胞和血小板的恢复更快。在此，我们报告了 27 例血液系统恶性肿瘤患者的移植结果，这些患者在接受低强度预处理（RIC）后，除了未处理的 CB 外，还接受了 1 个用 MPC 体外扩增的 CB 单位（MPC 组）。该组的结果与接受 2 个未处理的 CB 单位的 51 例历史对照（对照组）进行了比较。分析分为 2 个 RIC 治疗组：（1）全身照射 200cGy+环磷酰胺+氟达拉滨（TCF），和（2）氟达拉滨+美法仑（FM）。CB 与 MPC 共培养可使总核细胞中位数扩增 12 倍，CD34+细胞中位数扩增 49 倍。在发生植入的患者中，MPC 组中性粒细胞植入的中位时间为 12 天，而对照组为 16 天（P=0.02）。在接受 RIC 的两组患者中均观察到更快的中性粒细胞植入。在接受 FM 作为 RIC 方案的患者中，接受和未接受扩展的患者在第 26 天的中性粒细胞植入累积发生率分别为 75%和 50%（P=0.03）。如果接受 TCF 治疗，MPC 组和对照组的中性粒细胞植入发生率相似（82%对 79%，P=0.40）。即使在 RIC 方案后，用 MPC 扩增的 CB 单位移植是安全有效的，且中性粒细胞植入更快。
