Peripheral blood haploidentical hematopoietic stem cell transplantation for treatment of acute lymphoblastic leukemia in adults: monitoring minimal residual diseases to intervene recurrence

doi:10.3969/j.issn.2095-4344.0473

Abstract

Abstract:

BACKGROUND: Recurrence of acute leukemia after hematopoietic stem cell transplantation is one of the major problems affecting the long-term survival of patients. Early intervention to prevent ALL recurrence after transplantation can improve disease-free survival, overall survival and reduce post-transplant mortality. Monitoring of minimal residual disease (MRD) by flow cytometry and PCR-based molecular biology techniques is a widely reliable and practicable method.
OBJECTIVE: To dynamically monitor the MRD level of acute lymphoblastic leukemia after peripheral blood haploidentical hematopoietic stem cell transplantation and to explore its implications for predicting early relapse.
METHODS: A retrospective study was conducted in 53 patients with acute lymphoblastic leukemia who had underwgone peripheral blood haploidentical hematopoietic stem cell transplantation at the First Affiliated Hospital of Zhengzhou University from June 2011 to June 2017. The patients were followed up for postoperative 1, 3, 6, 12 months to observe the relation between MRD levels and relapse after transplantation.
RESULTS AND CONCLUSION: (1) The disease-free survival rate of MRD positive group and MRD negative group were 20.0% and 65.8%, respectively; and the overall survival rates were 50.8% and 68.9% in the two groups, respectively. There were significant differences between two groups. (2) Among 16 MRD positive patients accepting clinical intervention after transplantation, 4 patients presented with MRD negative and had no recurrence. (3) Eleven hematologic recurrence patients were given tyrosine kinase inhibitor-targeted therapy, chemotherapy, donor lymphocytes Infusion and secondary transplantation, but they eventually died. The median time from the discovery of MRD positive to hematologic recurrence was 100 (7-190) days, and during this period. Clinical intervention was confirmed to extend the recurrence time. In this study, one case refused clinical intervention, and eventually died of recurrence. Our findings indicate that dynamic monitoring of the MRD level in acute lymphoblastic leukemia patients after peripheral blood haploidentical transplantation can predict recurrence, by which the patients can be given early intervention to reduce the risk of recurrence and improve disease-free survival and overall survival.

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

Key words: Hematopoietic Stem Cell Transplantation, Leukemia, Biphenotypic, Acute, Recurrence, Tissue Engineering

CLC Number:

R394.2

Wan Ding-ming, Sun Lin-lin, Xie Xin-sheng, Guo Rong, Cao Wei-jie, Zhang Su-ping, Li Li, Chen Xiao-na, Liu Yu-ye. Peripheral blood haploidentical hematopoietic stem cell transplantation for treatment of acute lymphoblastic leukemia in adults: monitoring minimal residual diseases to intervene recurrence[J]. Chinese Journal of Tissue Engineering Research, 2018, 22(9): 1413-1418.

Figures/Tables 1

2.1 研究对象入组流程图见图1。 2.2 造血重建时间 53例外周血单倍体造血干细胞移植急性淋巴细胞白血病患者中，中性粒细胞植入平均中位时间为12(9-15) d，血小板植入平均中位时间为15(12-18) d。 2.3 移植后并发症移植后，26例出现移植物抗宿主病，10例出现出血性膀胱炎，13例出现细菌或/和真菌感染。 2.4 移植后微小残留病阴性患者的预后移植后骨髓微小残留病持续阴性者37例，血液学持续完全缓解状态，其中19例发生移植物抗宿主病(10例肠道移植物抗宿主病，8例皮肤移植物抗宿主病，1例肝脏移植物抗宿主病），8例患者发生出血性膀胱炎，该组患者的1年无病生存率为65.8%(图2)，1年总体生存率为68.9%(图3)。 2.5 移植后微小残留病阳性患者的预后移植后骨髓微小残留病阳性患者16例。①移植后流式细胞术检测微小残留病阳性并干预组：9例急性淋巴细胞白血病患者出现微小残留病阳性或血液学复发，其中2例在0.5%-1.0%水平的患者，分别给予“减停免疫抑制剂、地西他滨去甲基化治疗”后微小残留病转阴，未再复发。1例在0.5%-1.0%水平的患者拒绝治疗，最终复发死亡。6例患者血液学复发的同时合并微小残留病阳性，其中1例化疗，4例化疗联合供者淋巴细胞输注，1例二次移植，最终均复发死亡；②移植后BCR/ABL基因阳性并干预组：7例费城染色体阳性的急性淋巴细胞白血病患者单倍体造血干细胞移植后BCR/ABL基因表达水平转阳给予干预，其中2例应用酪氨酸激酶抑制剂，1例联合减停免疫抑制剂，4例联合化疗和酪氨酸激酶抑制剂治疗。2例患者BCR/ABL基因表达水平转阴，5例患者未转阴并出现血液学复发，距离复发时间100(7-190)d；③7例患者发生移植物抗宿主病(5例皮肤移植物抗宿主病，2例肠道移植物抗宿主病)，6例患者发生出血性膀胱炎，该组患者的1年无病生存率为20.0%(图2)，1年总体生存率为50.8%(图3)。"

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