Zhao K, Huang F, Chen X Y, Chang Y, Xu N, Shi P C, Liu H, Sun J, Xiang P, Liu Q F, Fan Z P
Department of Hematology, Nanfang Hospital, Southern Medical University, Gangzhou 510515, China.
Center for Stem Cell Biology and Tissue Engineering, Sun Yat-Sen University, Guangzhou 510080, China.
Zhonghua Xue Ye Xue Za Zhi. 2022 Jun 14;43(6):488-493. doi: 10.3760/cma.j.issn.0253-2727.2022.06.008.
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) . 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. 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 5.2×10(8) copies/L, =0.016; 3170.0×10(4) copies/L 0.2×10(4) copies/L, =0.006, respectively) , while JCV-DNA did not significantly differ when compared to before treatment (=0.106) . ④ No adverse reactions related to MSC infusion occurred in any of the 20 patients. Third-party bone marrow-derived MSC has significant efficacy and good safety in the treatment of refractory LOHC after allogeneic HSCT.
探讨第三方骨髓间充质干细胞（MSCs）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）的疗效及安全性。20例难治性LOHC患者接受常规治疗并联合应用来自第三方供者骨髓的MSCs。MSCs通过静脉输注，剂量为1×10(6) 个细胞/kg，每周1次，直至症状改善或连续输注4次后LOHC无变化。在MSCs输注前及输注后8周，通过实时定量PCR检测BK病毒尿（BKV）-DNA、JC病毒尿（JCV）-DNA和巨细胞病毒（CMV）-DNA。①20例难治性LOHC患者中，男性15例，女性5例，中位年龄为35（15 - 56）岁。其中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状细胞肿瘤（BPDCN）1例。HLA全相合移植4例，HLA不全相合移植16例。②每位患者MSCs输注的中位次数为3次（范围：2 - 8次）。17例患者治疗后达到完全缓解，1例部分缓解。总缓解率为90%。移植后中位随访期为397.5天（范围39 - 937天），13例患者存活，7例死亡。死亡原因包括急性移植物抗宿主病（aGVHD，1例）、感染（5例）和血栓性微血管病（TMA，1例）。③MSCs输注后第8周尿液中BKV - DNA和CMV - DNA的拷贝数显著低于治疗前（分别为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与治疗前相比差异无统计学意义（P = 0.106）。④20例患者中均未发生与MSCs输注相关的不良反应。第三方骨髓来源的MSCs治疗异基因HSCT后难治性LOHC具有显著疗效且安全性良好。
