Liu Xiaodan, Wu Meiqing, Peng Yanwen, Chen Xiaoyong, Sun Jing, Huang Fen, Fan Zhiping, Zhou Hongsheng, Wu Xiuli, Yu Guopan, Zhang Xian, Li Yonghua, Xiao Yang, Song Chaoyang, Xiang Andy Peng, Liu Qifa
Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Cell Transplant. 2014;23(9):1087-98. doi: 10.3727/096368912X661319.
Poor graft function (PGF) is a refractory complication that occurs after allogeneic hematopoietic stem cell transplantation (allo-HSCT). In the present study, we prospectively evaluated the efficacy and safety of mesenchymal stem cells (MSCs) expanded from the bone marrow of a third-party donor to patients with PGF after allo-HSCT. Twenty patients with PGF (7 with primary and 13 with secondary PGF) received MSCs (1 × 10(6)/kg) one to three times at 28-day intervals. Seventeen patients were responsive to MSCs, whereas three were not. Within the first 100 days after MSC treatment, 13 patients developed 20 episodes of infection. Moreover, five patients experienced cytomegalovirus-DNA viremia, and seven experienced Epstein-Barr virus (EBV)-DNA viremia within the first 100 days after MSC treatment; three of the latter developed EBV-associated posttransplant lymphoproliferative disorders (PTLD) within the follow-up period. Grade II acute graft-versus-host disease (GVHD) occurred in one patient, and local chronic GVHD occurred in two patients after receiving MSC treatment, including one acute GVHD and one chronic GVHD, respectively, after accepting donor lymphocyte infusions due to PTLD. After a follow-up period of an average of 508 days (range 166-904 days) posttransplantation, 11 patients died. No short-term toxic side effects were observed after MSC treatment. Two patients experienced leukemic relapse. With the exception of three patients with PTLD, no secondary tumors occurred. These results indicate that MSCs derived from the bone marrow of a third-party donor are beneficial in the treatment of both primary and secondary PGF that develops after allo-HSCT. However, additional studies will be needed to determine whether such treatment might increase the risk of EBV infection and reactivation or the development of EBV-associated PTLD.
移植功能不良（PGF）是异基因造血干细胞移植（allo-HSCT）后发生的一种难治性并发症。在本研究中，我们前瞻性评估了从第三方供体骨髓中扩增的间充质干细胞（MSCs）对allo-HSCT后发生PGF的患者的疗效和安全性。20例PGF患者（7例原发性PGF和13例继发性PGF）接受了MSCs（1×10(6)/kg），每隔28天输注1至3次。17例患者对MSCs有反应，3例无反应。在MSC治疗后的前100天内，13例患者发生了20次感染。此外，5例患者在MSC治疗后的前100天内出现巨细胞病毒DNA血症，7例出现 Epstein-Barr病毒（EBV）DNA血症；其中3例在随访期间发生了EBV相关的移植后淋巴细胞增殖性疾病（PTLD）。1例患者在接受MSC治疗后发生了Ⅱ级急性移植物抗宿主病（GVHD），2例患者发生了局部慢性GVHD，其中1例急性GVHD和1例慢性GVHD分别是在因PTLD接受供体淋巴细胞输注后发生的。移植后平均随访508天（范围166 - 904天），11例患者死亡。MSC治疗后未观察到短期毒性副作用。2例患者发生白血病复发。除3例PTLD患者外，未发生继发性肿瘤。这些结果表明，来自第三方供体骨髓的MSCs对allo-HSCT后发生的原发性和继发性PGF均有益。然而，需要进一步研究以确定这种治疗是否可能增加EBV感染和再激活的风险或EBV相关PTLD的发生风险。
