Department of Medicine, Division of Hematology, CHU of Liège, Liège, Belgium.
Biol Blood Marrow Transplant. 2010 Jun;16(6):838-47. doi: 10.1016/j.bbmt.2010.01.011. Epub 2010 Jan 28.
Recent studies have suggested that coinfusion of mesenchymal stem cells (MSCs) the day of hematopoietic cell transplantation (HCT) might promote engraftment and prevent graft-versus-host disease (GVHD) after myeloablative allogeneic HCT. This prompted us to investigate in a pilot study whether MSC infusion before HCT could allow nonmyeloablative (NMA) HCT (a transplant strategy based nearly exclusively on graft-versus-tumor effects for tumor eradication) from HLA-mismatched donors to be performed safely. Twenty patients with hematologic malignancies were given MSCs from third party unrelated donors 30-120 minutes before peripheral blood stem cells (PBSCs) from HLA-mismatched unrelated donors, after conditioning with 2 Gy total body irradiation (TBI) and fludarabine. The primary endpoint was safety, defined as a 100-day incidence of nonrelapse mortality (NRM) <35%. One patient had primary graft rejection, whereas the remaining 19 patients had sustained engraftment. The 100-day cumulative incidence of grade II-IV acute GVHD (aGVHD) was 35%, whereas 65% of the patients experienced moderate/severe chronic GVHD (cGVHD). One-year NRM (10%), relapse (30%), overall survival (OS) (80%) and progression-free survival (PFS) (60%), and 1-year incidence of death from GVHD or infection with GVHD (10%) were encouraging. These figures compare favorably with those observed in a historic group of 16 patients given HLA-mismatched PBSCs (but no MSCs) after NMA conditioning, which had a 1-year incidence of NRM of 37% (P = .02), a 1-year incidence of relapse of 25% (NS), a 1-year OS and PFS of 44% (P = .02), and 38% (P = .1), respectively, and a 1-year rate of death from GVHD or infection with GVHD of 31% (P = .04). In conclusion, our data suggest that HLA-mismatched NMA HCT with MSC coinfusion appeared to be safe.
最近的研究表明，在造血细胞移植（HCT）当天输注间充质干细胞（MSCs）可能有助于植入，并预防异基因 HCT 后移植物抗宿主病（GVHD）。这促使我们在一项试点研究中探讨，在非清髓性（NMA）HCT 前输注 MSCs 是否可以使 HLA 错配供者的非清髓性（NMA）HCT（一种移植策略，几乎完全基于移植物抗肿瘤效应来消除肿瘤）安全进行。20 例血液系统恶性肿瘤患者在接受 HLA 错配无关供者的外周血干细胞（PBSC）前 30-120 分钟给予来自第三方无关供者的 MSCs，预处理方案为 2Gy 全身照射（TBI）和氟达拉滨。主要终点是安全性，定义为 100 天非复发死亡率（NRM）<35%。1 例患者发生原发性移植物排斥，其余 19 例患者持续植入。100 天累积 II-IV 级急性 GVHD（aGVHD）发生率为 35%，65%的患者发生中重度慢性 GVHD（cGVHD）。1 年 NRM（10%）、复发（30%）、总生存率（OS）（80%）和无进展生存率（PFS）（60%），以及 1 年因 GVHD 或 GVHD 感染导致的死亡率（10%）令人鼓舞。这些数据与 16 例接受 NMA 预处理后接受 HLA 错配 PBSC（但无 MSCs）的历史组患者的观察结果相比具有优势，后者 1 年 NRM 发生率为 37%（P=0.02），1 年复发率为 25%（NS），1 年 OS 和 PFS 率为 44%（P=0.02），以及 38%（P=0.1），分别为 1 年因 GVHD 或 GVHD 感染导致的死亡率为 31%（P=0.04）。总之，我们的数据表明，HLA 错配 NMA HCT 联合 MSC 输注似乎是安全的。
