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.
目的： 观察第三方骨髓来源间充质干细胞（MSC）治疗异基因造血干细胞移植（allo-HSCT）后难治性迟发性出血性膀胱炎（LOHC）的疗效和安全性。 方法： 回顾性分析2018年7月至2020年6月allo-HSCT后发生难治性LOHC 20例患者在常规治疗基础上联合第三方骨髓来源MSC治疗。MSC以每次1×10(6)/kg、每周1次输注，直至症状改善或连用4次无效停用。在MSC治疗前及治疗后第8周应用定量PCR法检测患者尿液标本中BK病毒（BKV）、JC病毒（JCV）、巨细胞病毒（CMV）。 结果： ①20例难治性LOHC患者中，男15例、女5例，中位年龄35（15～56）岁；急性淋巴细胞白血病（ALL）5例，急性髓系白血病（AML）9例，骨髓增生异常综合征（MDS）5例，母细胞性浆细胞样树突细胞瘤（BPDCN）1例；HLA全相合移植4例，HLA不全相合移植16例。②MSC输注中位次数为3（2～8）次。17例患者获得完全缓解，1例获得部分缓解，总缓解率为90.0%。移植后中位随访397.5（39～937）d，13例存活、7例死亡，死亡原因包括急性GVHD 1例、感染5例、血栓性微血管病（TMA）1例。③MSC输注后第8周尿BKV-DNA及CMV-DNA拷贝数较治疗前显著降低（11342.1×10(8)拷贝/L对5.2×10(8)拷贝/L，P＝0.016；3170.0×10(4)拷贝/L对0.2×10(4)拷贝/L，P＝0.006），而JCV-DNA与治疗前相比无明显改变（P＝0.106）。④未发生MSC输注相关不良反应。 结论： 第三方骨髓来源MSC对allo-HSCT后难治性LOHC具有显著疗效且安全性良好。.
Keywords: Allogeneic hematopoietic stem cell transplantation; Mesenchymal stromal cell; Refractory late-onset hemorrhagic cystitis.