Effectiveness of unrelated peripheral blood stem cell transplantation in the treatment of severe aplastic anemia

doi:10.3969/j.issn.2095-4344.2130

Abstract

Abstract:

BACKGROUND: The probability of obtaining sibling-matched hematopoietic stem cell transplantation donors for patients with severe aplastic anemia is less than 30%. With the recent improvement of unrelated peripheral blood stem cell transplantation, the efficacy of unrelated peripheral blood stem cell transplantation in the treatment of benign and malignant hematological diseases has reached a result similar to that of sibling-matched hematopoietic stem cell transplantation.

OBJECTIVE: To evaluate the efficacy and safety of unrelated peripheral blood stem cell transplantation in the treatment of severe aplastic anemia.

METHODS: A retrospective analysis was made in 25 severe aplastic anemia (type I and type II) patients who received unrelated peripheral blood stem cell transplantation from March 2014 to September 2019. All of them were sibling-matched hematopoietic stem cell transplantation-free patients who refused to accept immunosuppressive therapy. The transplantation pretreatment regimen was “fludarabine + cyclophosphamide + rabbit anti-human thymocyte globulin antibody”, and the prevention scheme of graft-versus-host disease was “cyclosporine + mycophenolate mofetil + short-term methotrexate”. The observation indicators included implantation rate, hematopoietic reconstitution time, incidence of graft-versus-host disease, incidence of transplantation-related complications, 5-year estimated overall survival rate and 5-year estimated disease-free survival rate. This study was approved by the Ethics Committee of the First Affiliated Hospital of Zhengzhou University. Patients and their family members signed the informed consent on unrelated peripheral blood stem cell transplantation.

RESULTS AND CONCLUSION: (1) Three of the 25 patients died within 28 days after hematopoietic stem cell transplantation, and the implantation could not be evaluated. Of the remaining 22 patients, 21 cases (95.4%) obtained hematopoietic reconstitution and the implantation was successful; 1 case (4.6%) failed. The median time of neutrophil ≥ 0.5×10⁹ L^-1 and platelet ≥ 20×10⁹ L^-1was 12 days (9-18 days) and 13 days (10-32 days), respectively. (2) Among the 21 patients with successful implantation, the incidence of acute graft-versus-host disease was 28.6% (6/21), including I-II degree in 3 cases and III–IV degree in 3 cases. There were only 9.5% patients with mild chronic graft-versus-host disease (2/21), and no moderate and severe chronic graft-versus-host disease occurred. (3) During the median follow-up of 396 days (15-1 886 days), 18 cases (72.0%) survived; the 5-year estimated overall survival rate was 71.1%; and the 5-year estimated disease-free survival rate was 65.6%. Totally 7 cases (28.0%) died, of which 3 cases (12.0%) died of infection, 2 cases (8.0%) died of acute intestinal graft-versus-host disease, 1 case (4.0%) died of intracranial hemorrhage, and 1 case (4.0%) died of multiple organ failure. (4) The results show that unrelated peripheral blood stem cell transplantation is a safe and effective treatment for severe aplastic anemia patients without sibling matching donor, and it is a feasible and useful alternative therapy.

Key words: stem cells, aplastic anemia, severe, hematopoietic stem cell transplantation, HLA-matched unrelated, implantation rate, graft-versus-host disease

CLC Number:

Zhang Suping, Sun Ling, Wan Dingming, Cao Weijie, Li Li, Liu Changfeng, Liu Yufeng, Wang Dao, Guo Rong, Jiang Zhongxing, Xie Xinsheng. Effectiveness of unrelated peripheral blood stem cell transplantation in the treatment of severe aplastic anemia[J]. Chinese Journal of Tissue Engineering Research, 2020, 24(31): 4994-5001.

Figures/Tables 5

2.6 移植相关并发症发生率 2.6.1 出血性膀胱炎发生情况 8例(32.0%)患者并发出血性膀胱炎，经治疗后均痊愈。 2.6.2 病毒感染发生情况 10例(40.0%)患者发生EB病毒血症，13例(52.0%)患者发生巨细胞病毒血症，经治疗后病毒滴度低于检测下限。1例(4.0%)患者发生巨细胞病毒性肺炎，2例(8.0%)患者发生巨细胞病毒性膀胱炎，应用更昔洛韦治疗后均治愈；1例(4.0%)患者发生巨细胞病毒性视网膜炎，应用静脉及眼内注射更昔洛韦治疗后好转，现除视力较前下降外，无其他并发症。 2.6.3 移植后淋巴增殖性疾病发生情况 1例(4.0%)患者发生移植后淋巴增殖性疾病，最初为病理类型早期病变(传染性单核细胞样移植后淋巴增殖性疾病)，经利妥昔单抗单药治疗无效后转为弥漫大B细胞淋巴瘤，应用RCHOP方案化疗联合放疗，目前存活。 2.6.4 可逆性后部脑病综合征发生情况 2例(8.0%)患者分别于移植后+31 d，+43 d发生可逆性后部脑病综合征，经治疗后痊愈。 2.6.5 植入不良发生情况 1例(4.0%)患者移植后继发血小板植入不良，应用艾曲波帕治疗2个月后血小板恢复正常。 2.7 患者死亡情况分析死亡患者共7例(28.0%)，其中3例(12.0%)患者死于感染，1例为43岁男性患者，诊断至接受移植的时间为62个月，于+14 d因耐碳青霉烯大肠埃希菌血流感染治疗无效死于感染性休克；1例患者植入失败，于+29 d死于解甘露醇罗尔斯顿菌血流感染；1例患者为Ⅲ度急性肝脏移植物抗宿主病，治疗后肝功能好转，但因并发肺部感染于移植后3个月死亡。2例(8.0%)患者死于Ⅳ度急性肠道移植物抗宿主病。1例(4.0%)患者死于颅内出血。1例(4.0%)患者死于多器官功能衰竭。7例患者均于移植后半年内死亡，移植半年后未再出现死亡患者。 "

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