Parental peripheral blood haploidentical hematopoietic stem cell transplantation in treatment of children with relapsed and refractory acute leukemia

doi:10.3969/j.issn.2095-4344.2014.32.026

Abstract

Abstract:

BACKGROUND: Children with relapsed and refractory acute leukemia have a very poor clinical effect by simple chemotherapy, and allogeneic hematopoietic stem cell transplantation is the only effective approach to cure the disease. Haploidentical hematopoietic stem cell transplantation is becoming gradually mature, and the data show it has gotten better clinical efficacy than identical sibling and unrelated matched hematopoietic stem cell transplantation. In addition, parents have high compliance in order to save the treatment interval, which ensures the stem cell number and prevents leukemia recurrence, significantly improving the transplantation success rate and long-term leukemia-free survival rate.
OBJECTIVE: To retrospectively analyze the clinical efficacy of parental peripheral blood haploidentical stem cell transplantation in treating children with relapsed and refractory acute leukemia.
METHODS: Thirty-five children with relapsed and refractory acute leukemia undergoing parental peripheral blood haploidentical stem cell transplantation were enrolled. “Modified 1,4-butanediol dimethanesulfonate/ cyclophosphamide+thymocyte immunoglobulin” conditioning regimen and triple therapy of methotrexate, cyclosporine A and mycophenolate mofetil were applied to prevent graft-versus-host disease.
RESULTS AND CONCLUSION: All the 35 patients achieved full engraftment. (1) The median mononuclear cells was 5.82(3.23-8.45)×108/kg, the median CD34+ cells was 4.52 (2.37-11.51)×106/kg. (2) Within 100 days after stem cell infusion, the transplant related mortality was 14.3%. (3) Incidence of I-II degrees of acute graft-versus-host disease was 34.3%, III-IV incidence was 37.1%, and the total incidence of chronic graft-versus-host disease was 42.9%. (4) The 2-year leukemia-free survival rate was 42.9%; the 2-year overall survival rate was 51.4%; the leukemia relapse rate was 34.3%; median survival time was 24 months. Results show that if there are no human leukocyte antigen-identical sibling and unrelated human leukocyte antigen-matched donors, parental haploidentical peripheral blood stem cell transplantation is an effective and feasible treatment for children with relapsed and refractory acute leukemia.

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

全文链接：

Key words: haploidy, peripheral blood stem cell transplantation, leukemia, stem cell transplantation

CLC Number:

R394.2

Wan Ding-ming, He Hai-yan, Bian Zhi-lei, Xie Xin-sheng, Sun Ling, Sun Hui, Cao Wei-jie,Xuan Zhong-qian, Liu Fei. Parental peripheral blood haploidentical hematopoietic stem cell transplantation in treatment of children with relapsed and refractory acute leukemia[J]. Chinese Journal of Tissue Engineering Research, 2014, 18(32): 5237-5243.

Figures/Tables 2

2.1 患者数量分析及患者临床信息共纳入35例儿童复发难治急性白血病行父母供者外周血单倍体造血干细胞移植，均进入结果分析，无数据脱落。患儿基本信息见表1。 2.2 儿童复发难治急性白血病患者的回输细胞数量回输单个核细胞中位数为5.82(3.23-8.45)×108/kg，CD34+细胞中位数4.52(2.37-11.51)×106/kg；其中3例患者回输外周血干细胞小于4×108/kg，10例患者CD34+细胞小于4×106/kg，患者造血干细胞仍植入成功。 2.3 儿童复发难治急性白血病患者的植入情况以持续 3 d中性粒细胞≥0.5×109 L-1，连续3 d不输注血小板，血小板≥20×109 L-1，作为造血功能重建的指标[18]。中性粒细胞中位植入时间为13(9-20) d，血小板中位植入时间14(10-58) d。所有患者经微卫星标记、性染色体及血型检测为完全供者嵌合体[35-36]，证明造血重建成功。 2.4 儿童复发难治急性白血病患者的移植物抗宿主病发生情况干细胞回输后前100 d内35例患儿中23例出现急性移植物抗宿主病，发生中位时间为48.5(27-85) d，其中Ⅰ-Ⅱ度12例，8例以皮肤为主，4例以肠道为主，发生率为34.3%；Ⅲ-Ⅳ度13例，3例以皮肤为主，9例以肠道为主，1例以肝脏为主，发生率为37.1%；急性移植物抗宿主病累积发生率为65.7%；干细胞回输后随访2-47个月，15例出现不同脏器不同程度慢性移植物抗宿主病，发生时间中位数为121(98-360) d，其中4例广泛型皮肤慢性移植物抗宿主病，11例为局限型慢性移植物抗宿主病，多见于口、眼、皮肤，总发生率42.9%。发生移植物抗宿主病的患儿中2例死于腹泻，均为急性肠道排斥反应。 2.5 儿童复发难治急性白血病患者的原发病复发情况随访至2014年1月，移植后半年内共有6例复发，均为骨髓象复发，3例为急性B淋巴细胞白血病(BCR/ABL阳性)，2例为复发B急淋，1例为慢粒急淋变；移植半年后6例复发，其中2例为复发急性B淋巴细胞白血病中枢神经系统侵犯，接受放疗，2例M5为粒细胞肉瘤，给予化疗+放疗；2例骨髓象复发，1例为M2合并BCR/ABL阳性，1例为复发B急淋。总复发率达34.3%。 2.6 儿童复发难治急性白血病患者的不良反应儿童复发难治急性白血病行父母供者外周血单倍体造血干细胞移植35例，6例死于重度感染(其中肺部感染3例，肠道感染1例，中枢神经系统感染2例)；2例死于超急性移植物抗宿主病肠道反应；1例死于移植后淋巴细胞增殖性疾病；1例因应用蒽环类药物导致心肌损伤，进而心脏骤停；2例患儿出现癫痫样抽搐；2例发生皮肤黑曲霉菌感染，其中1例死于多脏器功能衰竭；2例发生纯红再障，分别在干细胞移植后7个月，11个月后血红蛋白恢复至正常范围。 2.7 儿童复发难治急性白血病患者的临床疗效 35例患者随访2-47个月，移植相关死亡率14.3%，2年无白血病生存率为42.9%，2年总体生存率为51.4%，中位生存时间为25个月；生存曲线见图1。"

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