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[自体外周造血干细胞移植(AHSCT)后免疫重建的初步评估]

[Preliminary assessment of immune reconstitution after autologous peripheral hematopoietic stem cell transplantation (AHSCT)].

作者信息

Huang Hui-Qiang, Cai Qi-Chun, Shi Yan-Xia, Lin Xu-Bin, Wei Jing, Guo Ying, Pan Zhan-He

机构信息

State Key Laboratory of Oncology in South China, Guangzhou, Guangdong, 510060, P. R. China.

出版信息

Ai Zheng. 2006 Aug;25(8):1023-8.

Abstract

BACKGROUND & OBJECTIVES: Though high dose chemo-therapy combined with autologous hematopoietic stem cell transplantation (AHSCT) has made great progress on the treatment of chemo-sensitive malignant tumors, the relapse rate remains high. Successful immune reconstitution after AHSCT may reduce recurrence; therefore this study was to explore the characteristics of immune reconstitution after AHSCT and assess its feasibility in clinical use.

METHODS

Twenty four cases after AHSCT were enrolled in our study. There were 19 Non-hodgkin Lymphoma (NHL), 3 Hodgkin Lymphoma (HD) and 2 rhabdomyosarcoma. Nineteen cases had achieved complete remission (CR) while 5 partial remission (PR) before AHSCT. All cases were administered Interleukin (IL)-2 and Interferon (IFN)-alpha after AHSCT. Some patients were given thymus factor and/or CIK infusion. Phenotypes of peripheral blood T, B, NK subsets and immunological profile of TH1/TH2 by intracellular staining of cytokines after PMA/ionomycin stimulation were evaluated.

RESULTS

75% of the cases achieved CR while 4.17% were progression of disease (PD) and 16.67% were relapsed during the median follow-up time of 12 (2-60) months. The changes of immune parameters after AHSCT were as followed: (1) CD4+T cells (normal control 33.5+/-6.9%) started to decrease dramatically one month after AHSCT, which was 2.5-13% (median rate 5.6%)in the 2nd month; and then slowly increased to 10-20% in the 7th month, but did not return back to normal even after one year in all patients. In addition, reversed ratio of CD4/CD8 lasted for a long period of time. B cells also began to decrease 1 month after AHSCT, and recovered to normal in the 4th month. But B cells remained 0% in the 6th month and 1% in 12th month in patients treated by rituximab before receiving AHSCT. The ratio of NK cells was 10-20% (higher than normal controls) in the 2nd month, then returned to normal thereafter. (2) The cytokine secretion by T cell: there were 48.79% patients whose TH1 was lower than normal controls or at the lower limit of normal range. All the patients with normal TH1 were treated by IFN-alpha or CIK cell infusion. TH2 was much higher than normal level among 68.29% cases and this abnormality lasted at least for 1 year in some cases. TH2 at normal range was only observed in cases receiving IFN-alpha treatment. Furthermore, IFN-alpha could significantly decrease TH2 level. (3) Increasing tendency of CD4+CD25+/CD4+, CD4+CD69+/CD4+ ratio was observed in patients received additional thymus factor treatment compared to those did not.

CONCLUSIONS

Administration of CIK cells, thymus factor, IL-2 and IFN-alpha after AHSCT could improve the immunologic function of patients, and TH1/TH2 ratio may virtually reflect the immune status of patients. However more information is required to make prognostic assessments of immune reconstruction and the long-term survival rate.

摘要

背景与目的

尽管大剂量化疗联合自体造血干细胞移植(AHSCT)在化疗敏感恶性肿瘤的治疗上取得了很大进展,但复发率仍然很高。AHSCT后成功的免疫重建可能会降低复发率;因此,本研究旨在探讨AHSCT后免疫重建的特点,并评估其在临床应用中的可行性。

方法

本研究纳入了24例AHSCT后的患者。其中非霍奇金淋巴瘤(NHL)19例、霍奇金淋巴瘤(HD)3例、横纹肌肉瘤2例。19例在AHSCT前达到完全缓解(CR),5例为部分缓解(PR)。所有患者在AHSCT后均给予白细胞介素(IL)-2和α干扰素(IFN)治疗。部分患者给予胸腺因子和/或CIK细胞输注。通过PMA/离子霉素刺激后细胞内细胞因子染色评估外周血T、B、NK亚群的表型以及TH1/TH2的免疫谱。

结果

在中位随访时间12(2 - 60)个月期间,75%的病例达到CR,4.17%疾病进展(PD),16.67%复发。AHSCT后免疫参数的变化如下:(1)CD4 + T细胞(正常对照为33.5±6.9%)在AHSCT后1个月开始急剧下降,第2个月下降2.5 - 13%(中位下降率5.6%);然后在第7个月缓慢上升至10 - 20%,但所有患者即使1年后也未恢复正常。此外,CD4/CD8的倒置比率持续较长时间。B细胞在AHSCT后1个月也开始下降,并在第4个月恢复正常。但在接受AHSCT前接受利妥昔单抗治疗的患者中,B细胞在第6个月仍为0%,在第12个月为1%。NK细胞比例在第2个月为10 - 20%(高于正常对照),此后恢复正常。(2)T细胞分泌的细胞因子:48.79%的患者TH1低于正常对照或处于正常范围下限。所有TH1正常的患者均接受了IFN - α或CIK细胞输注治疗。68.29%的病例中TH2远高于正常水平,且在某些病例中这种异常至少持续1年。仅在接受IFN - α治疗的病例中观察到TH2处于正常范围。此外,IFN - α可显著降低TH2水平。(3)与未接受额外胸腺因子治疗的患者相比,接受额外胸腺因子治疗的患者中CD4 + CD25 + /CD4 +、CD4 + CD69 + /CD4 +比例有上升趋势。

结论

AHSCT后给予CIK细胞、胸腺因子、IL - 2和IFN - α可改善患者的免疫功能,TH1/TH2比率可能切实反映患者的免疫状态。然而,需要更多信息来对免疫重建和长期生存率进行预后评估。

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