Cotransplantation of haploidentical hematopoietic and umbilical cord mesenchymal stem cells with a myeloablative regimen for refractory/relapsed hematologic malignancy

Yamei Wu, Zhihong Wang, Yongbin Cao, Lixin Xu, Xiaohong Li, Pei Liu, Pei Yan, Zhouyang Liu, Dandan Zhao, Jing Wang, Xiaoxiong Wu, Chunji Gao, Wanming Da, Zhongchao Han

Human leukocyte antigen haploidentical hematopoietic stem-cell transplantation (haplo-HSCT) is associated with an increased risk of graft failure and severe graft-versus-host disease (GVHD). Mesenchymal stromal cells (MSCs) have been shown to support in vivo normal hematopoiesis and to display potent immunesuppressive effects. We cotransplanted the culture-expanded third-party donor-derived umbilical cord MSCs (UC-MSCs) in 50 people with refractory/relapsed hematologic malignancy undergoing haplo-HSCT with myeloablative conditioning. We observed that all patients given MSCs showed sustained hematopoietic engraftment without any adverse UC-MSC infusion-related reaction. The median times to neutrophil >0.50 × 10(9)/L and platelet >20 × 10(9)/L engraftment were 12.0 and 15.0 days, respectively. We did not observe an increase in severe acute GVHD (aGVHD) and extensive chronic GVHD (cGVHD), too. Grade II-IV aGVHD was observed in 12 of 50 (24.0 %) patients. cGVHD was observed in 17 of 45 (37.7 %) patients and was extensive in 3 patients. Additionally, only five patients (10.0 %) experienced relapse at a median time to progression of 192 days. The probability that patients would attain progression-free survival at 2 years was 66.0 %. The results indicate that this new strategy is effective in improving donor engraftment and reducing severe GVHD, which will provide a feasible option for the therapy of high-risk hematologic malignancy.