第三方骨髓来源间充质干细胞治疗异基因造血干细胞移植后难治性迟发性出血性膀胱炎20例临床研究

OBJECTIVE: To examine the efficacy and safety of third-party bone marrow-derived mesenchymal stem cells (MSCs) in the treatment of refractory delayed hemorrhagic cystitis (LOHC) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: Twenty patients with refractory LOHC received conventional therapy combined with MSCs obtained from third-party donors' bone marrow (BM). MSCs were given intravenously at a dose of 1 × 10(6) cells/kg once weekly until either the symptoms improved or no changes in LOHC were seen after continuous infusion four times. BK viruria (BKV)-DNA, JC viruria (JCV)-DNA, and CMV-DNA were detected by real-time quantitative PCR before and 8 weeks after the MSCs infusion. RESULTS: ① Of the 20 patients with refractory LOHC, 15 were males, and 5 were females, and the median age was 35 (15–56) years. There were 5 cases of acute lymphoblastic leukemia (ALL), 9 cases of acute myeloid leukemia (AML), 5 cases of myelodysplastic syndrome (MDS), and 1 case of maternal plasma cell like dendritic cell tumor (BPDCN). There were 4 cases of HLA identical transplantation and 16 cases of HLA incomplete transplantation. ②The median number of MSC infusions for each patient was 3 (range: 2–8). Seventeen patients achieved complete response, and one had a partial response after treatment. The overall response rate was 90%. Over a median follow-up period of 397.5 days (range 39–937 days) post-transplantations, 13 patients survived, and 7 died. The causes of death included aGVHD (1 case), infections (5 cases), and TMA (1 case). ③The copy numbers of BKV-DNA and CMV-DNA in urine in the 8th week after MSCs infusion were significantly lower than those observed before treatment (11342.1×10(8) copies/L vs 5.2×10(8) copies/L, P＝0.016; 3170.0×10(4) copies/L vs 0.2×10(4) copies/L, P＝0.006, respectively), while JCV-DNA did not significantly differ when compared to before treatment (P＝0.106). ④ No adverse reactions related to MSC infusion occurred in any of the 20 patients. CONCLUSION: Third-party bone marrow-derived MSC has significant efficacy and good safety in the treatment of refractory LOHC after allogeneic HSCT.