脐血联合单倍体造血干细胞移植治疗恶性血液病的疗效及安全性分析

Efficacy and safety analysis of umbilical cord blood combined with haploid hematopoietic stem cell transplantation in the treatment of malignant hematological malignancies

目的探讨脐血联合单倍体造血干细胞移植(haplo-cord HSCT)治疗恶性血液病的疗效及安全性。方法回顾性分析郑州大学附属肿瘤医院2017年1月至2021年6月接受haplo-cord HSCT的82例恶性血液病患者的临床资料。男52例,女30例,年龄[M(Q_(1),Q_(3))]为29(20,41)岁。所有患者采用清髓性预处理方案,以回输供者干细胞当天记为0 d,回输前1天记为-1 d,回输后1天记为+1 d,依此类推。82例患者在接受清髓性预处理后回输非血缘脐血及单倍体供者外周血干细胞和(或)骨髓干细胞。移植物抗宿主病(GVHD)预防方案为8 mg/kg兔抗人胸腺细胞免疫球蛋白(ATG)联合环孢素、吗替麦考酚酯、甲氨蝶呤。评估患者植入情况和GVHD、感染、出血性膀胱炎等移植相关并发症发生情况,以及患者远期生存情况。结果移植后粒系、巨核系植入时间[M(Q_(1),Q_(3))]分别为13(11,15)、15(13,21)d,+30 d粒系累积植入率为98.8%(81/82),+100 d巨核系累积植入率为92.7%(76/82)。移植后Ⅱ~Ⅳ、Ⅲ~Ⅳ度急性GVHD累积发生率分别为24.4%(20/82)、6.1%(5/82),+18个月内慢性GVHD累积发生率为13.5%(11/82)。移植后随访时间[M(Q_(1),Q_(3))]为26(13,41)个月,3年总生存率为70.5%(95%CI:59.7%~81.3%),无事件生存率为66.1%(95%CI:56.1%~76.1%),累积复发率为6.3%(95%CI:5.7%~26.9%),非复发死亡率为20.8%(95%CI:12.0%~29.6%)。移植后巨细胞病毒、EB病毒重新激活的累积发生率分别为37.8%(31/82)、14.6%(12/82)。移植后出血性膀胱炎的累积发生率为32.9%(27/82)。结论haplo-cord HSCT治疗恶性血液病疗效较好,移植后造血重建迅速,GVHD以及病毒感染发生率均较低。

Objective To investigate the efficacy and safety of umbilical cord blood combined with haploid HSCT(haplo-cord HSCT)in the treatment of hematological malignancies.Methods The data of 82 patients with hematologic malignancies who received haplo-cord HSCT from January 2017 to June 2021 in the Affiliated Cancer Hospital of Zhengzhou University were retrospectively analyzed.There were 52 male and 30 female patients,aged[M(Q_(1),Q_(3))]29(20,41)years.All patients received myeloablative preconditioning regimen.The day of the donor stem cell infusion was recorded as day 0(0 d),the day before the infusion was recorded as day-1(-1 d),and the day after the infusion was recorded as day+1(+1 d),and so on.Eighty-two patients received transfusion of peripheral blood and/or bone marrow stem cells from unrelated cord blood and haplotype donors after the myeloablative preconditioning regimen.The graft-versus-host disease(GVHD)prophylaxis regimen was 8 mg/kg ATG combined with cyclosporine,morte-macrolide,and methotrexate.Patients were evaluated for implantation and the occurrence of transplant-related complications such as GVHD,infection,hemorrhagic cystitis,and long-term patient survival.Results The time of neutrophil engraftment[M(Q_(1),Q_(3))]was 13(11,15)days and 15(13,21)days for platelet.The 30-day cumulative incidence of neutrophil engraftment was 98.8%(81/82)and 100-day cumulative incidence of platelet engraftment was 92.7%(76/82).The cumulative incidence of acute graft-versus-host disease(aGVHD)in degreeⅡ-ⅣandⅢ-Ⅳwas 24.4%(20/82)and 6.1%(5/82),respectively.The cumulative incidence of chronic GVHD in+18 months was 13.5%(11/82).The follow-up time[M(Q_(1),Q_(3))]was 26(13,41)months,and the overall survival(OS)rate,event-free survival(EFS)rate,cumulative recurrence rate(CIR)and non-recurrence mortality(NRM)rate at 3 years after transplantation were 70.5%(95%CI:59.7%-81.3%),66.1%(95%CI:56.1%-76.1%),6.3%(95%CI:5.7%-26.9%)and 20.8%(95%CI:12.0%-29.6%),respectively.The cumulative incidence of cytomegalovirus and EBV reactivation was 37.8%(31/82)and 14.6%(12/82),respectively.The cumulative incidence of hemorrhagic cystitis was 32.9%(27/82).Conclusion The efficacy of haplo-cord HSCT in the treatment of hematologic malignancies is reliable,with rapid hematopoietic reconstitution,low incidence of GVHD and virus reactivation.