中国组织工程研究

中国组织工程研究 ›› 2017, Vol. 21 ›› Issue (25): 4044-4049.doi: 10.3969/j.issn.2095-4344.2017.25.018

• 干细胞移植 stem cell transplantation • 上一篇    下一篇

同胞全相合、无关供体全相合及亲缘间单倍型异基因造血干细胞移植治疗伴有费城染色体急性淋巴细胞白血病：疗效和安全性

胡晓慧1，周 洁2，周海侠1，张 日1，吴德沛1   

  1. 1苏州大学附属第一医院，江苏省血液研究所，卫生部血栓与止血重点实验室，血液学协同创新中心，江苏省苏州市 215006；2苏州市市立医院ICU，江苏省苏州市  215008
  • 修回日期:2017-07-19 出版日期:2017-09-08 发布日期:2017-10-09
  • 通讯作者: 张日，博士生导师，主任医师，苏州大学附属第一医院，江苏省血液研究所，卫生部血栓与止血重点实验室，血液学协同创新中心，江苏省苏州市 215006
  • 作者简介:胡晓慧，女，1976年生，内蒙古自治区赤峰市人，满族，2005年苏州大学毕业，博士，副主任医师，硕士生导师，主要从事造血干细胞移植相关研究。
  • 基金资助:

    江苏省科教兴卫工程-临床医学中心(ZX201102)；国家临床重点专科建设项目；卫生公益性行业科研专项经费项目(201202017)

Different types of allogeneic hematopoietic stem cell transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia: therapeutic efficacy and safety

Hu Xiao-hui1, Zhou Jie2, Zhou Hai-xia1, Zhang Ri1, Wu De-pei1   

  1. 1Jiangsu Provincial Hematology Institute, First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China; 2ICU, Suzhou Municipal Hospital, Suzhou 215008, Jiangsu Province, China
  • Revised:2017-07-19 Online:2017-09-08 Published:2017-10-09
  • Contact: Zhang Ri, Doctoral supervisor, Chief physician, Jiangsu Provincial Hematology Institute, First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
  • About author:Hu Xiao-hui, M.D., Associate chief physician, Master’s supervisor, Jiangsu Provincial Hematology Institute, First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
  • Supported by:

    Jiangsu Province Science and Education Project for Medicine Revitalization - Clinical Medicine Center, No. ZX201102; National Clinical Specialist Construction Projects; Health and Public Welfare Special Funds, No. 201202017

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摘要：

文章快速阅读：

文题释义：
造血干细胞移植：将正常供体或自体的造血细胞经血管输注给经过一定措施处理过的患者。这些处理措施包括全身照射、化疗和必要的免疫抑制治疗，输注后受者获得具有增殖、分化为各系成熟血细胞的功能和自我更新能力的造血干细胞，将会重建正常造血功能和免疫功能，维持持续造血。
移植物抗宿主病：是异基因造血干细胞移植最主要的并发症。正常个体之间组织的转植可导致宿主针对移植物的免疫反应，造成外来组织被识别和被排斥。同时包含在移植物中的免疫活性细胞可造成移植物抗宿主方向上的免疫反应，包括急性和慢性两大类。

 

摘要
背景：随着移植方案的优化及移植物抗宿主病治疗药物的出现，使得异基因造血干细胞移植近年来取得了巨大的进步，为越来越多的恶性血液病患者争取了长期生存的机会。
目的：比较3种移植方式即同胞全相合、无关供体全相合及亲缘间单倍型异基因造血干细胞移植治疗伴有费城染色体急性淋巴细胞白血病(Ph+ALL)的疗效和安全性。
方法：2006年6月至2013年11月间，69例伴有费城染色体急性淋巴细胞白血病患者接受异基因造血干细胞移植。同胞全相合移植23例，无关供体全相合移植24例，亲缘间单倍型移植22例；其中54例为CR1状态，12例为CR2到CR4状态，3例复发状态。获取供者骨髓干细胞或者外周血干细胞用于移植。预处理方案为阿糖胞苷、白消安、环磷酰胺及全身照射等。联合使用环孢素A+短程甲氨蝶呤+吗替麦考酚酯+抗人胸腺细胞球蛋白等预防移植物抗宿主病。
结果与结论：①68例患者获得造血重建，仅1例单倍型植入失败；②患者随访时间中位数为20.4个月，同胞全相合、无关供体全相合及亲缘间单倍型移植的急性移植物抗宿主病发生率分别为30%，33%及45%，慢性移植物抗宿主病发生率22%，29%及36%，各组间急性移植物抗宿主病、慢性移植物抗宿主病发生率比较差异无显著性意义；③同胞全相合、无关供体全相合及亲缘间单倍型移植的移植相关死亡率为9%，29%及41%，各组间比较差异有显著性意义(0.01< P < 0.05)。复发率为17%，21%及14%，各组间比较差异无显著性意义；④同胞全相合、无关供体全相合及亲缘间单倍型移植的3年总体生存率为68%，49%及43%，同胞全相合组与无关供体全相合组、同胞全相合与亲缘单倍型组分别比较，差异有显著性意义(P均< 0.05)，而无关供体全相合与亲缘间单倍型移植比较差异无显著性意义；⑤54例CR1状态移植患者3年总体生存率为58%；15例于非CR1状态移植患者3年总体生存率为41%；⑥结果表明，同胞全相合移植疗效优于无关供体全相合及单倍型移植；CR1状态下行异基因造血干细胞移植的疗效显著优于CR2以上状态。

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
ORCID: 0000-0001-8688-0595(胡晓慧)

关键词: 干细胞, 移植, 费城染色体, 急性淋巴细胞白血病, 造血干细胞移植, 同胞全相合, 无关供体全相合, 单倍型

Abstract:

BACKGROUND: With the optimization of transplantation scheme and the emergence of graft-versus-host disease (GVHD) therapy drugs, allogeneic hematopoietic stem cell transplantation (allo-HSCT) in recent years has made great progress that makes patients with hematological malignancies have more long-term survival opportunities.
OBJECTIVE: To compare the efficiency and safety of three types of allo-HSCT used in the treatment of adults with Philadelphia chromosome (Ph) in acute lymphoblastic leukemia (Ph+ALL).
METHODS: A total of 69 patients with Ph+ALL who received allo-HSCT from June 2006 to November 2013 were enrolled, including 23 cases of sib-matched donor transplantation, 24 cases of unrelated-matched donor transplantation, and 22 cases of haploidentical donor transplantation. There were 54 cases of CR1, 13 cases of CR2 to CR3 and 3 cases of relapse. The bone marrow or/and peripheral blood stem cells were used for transplantation. All patients were subjected to pretreatment consisting of cytarabine, busulfan, cyclophosphamide and total body irradiation. GVHD was prevented by combined use of immunosuppressants including cyclosporine A, short-term methotrexate, mycophenolate mofetil and anti-human thymocyte globulin, etc.
RESULTS AND CONCLUSION: The results showed that 68 patients acquired hematopoietic reconstitution, and only 1 case of haploidentical donor transplantation failed. The mean follow-up period was 20.4 months. The acute GVHD incidence of the sibling matched-HSCT, unrelated donor HSCT and related haploidentical allo-HSCT was 30%, 33% and 45%, respectively; the chronic GVHD incidence (cGVHD) incidence was 22%, 29% and 36%, respectively; the incidence of aGVHD and cGVHD between groups showed no statistically significant difference. Transplant related mortality (TRM) was 9%, 29% and 41%, respectively, and there was a significant difference among groups (0.01 < P < 0.05). Recurrence rates were 17%, 21% and 14%, respectively, and there was no significant difference among groups. The 3-year overall survival rates were 68%, 49% and 43%, respectively; there were significant differences between sib-matched-HSCT and the other two groups, but no statistically significant difference was found between unrelated donor HSCT and related haploidentical allo-HSCT groups. The 3-year overall survival rate was 58% for 54 patients in CR1 and 41% for 15 patients in non-CR1 states. To conclude, the sib-matched HSCT has better effect than unrelated donor transplantation and related haploidentical allo-HSCT; Ph+ALL patients should do transplantation as early as possible in the state of CR1.

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: Philadelphia Chromosome, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Hematopoietic Stem Cell Transplantation, Tissue Engineering

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