【摘要】 背景与目的:超大剂量化疗联合自体造血干细胞移植(autologoushematopoieticstemcelltransplantion,AHSCT)治疗化疗敏感肿瘤已取得长足的进步,但复发率仍较高,有效的移植后免疫重建可能减少复发,因此,对AHSCT后患者采用多种免疫制剂联合治疗,并进行免疫功能监测,评估各种免疫制剂对免疫功能的影响,初步探讨AHSCT后免疫重建的规律,以及免疫治疗的可行性。方法:选择AHSCT后2个月内或移植后复发病例共24例,其中非霍奇金淋巴瘤(NHL)19例,霍奇金淋巴瘤(HD)3例,青少年横纹肌肉瘤2例;主要采用IL-2联合IFN-α治疗,6例患者予胸腺因子和CIK细胞治疗。结果:中位随访期12个月(2～60个月),持续CR75.0%。免疫指标改变如下:(1)淋巴细胞亚群:CD4+T细胞[健康对照为(33.5±6.9)%]于移植后1个多月开始显著下降,2个月时约2.5%～13.0%(中位5.6%),此后逐步回升,7个月时仅为10.0%～20.0%,1年后全部患者仍低于正常,CD4/CD8比率持续倒置。B细胞在移植后1个多月开始下降,4个月时基本恢复正常;但移植前用美罗华治疗的病例直到移植后半年和1年仍为0及1%。NK细胞比例于移植后2个月约10.0%～20.0%(比正常值稍高),此后逐渐下降至正常。(2)T细胞细胞因子分泌:TH1,48.79%患者低于或处于正常低值;处于正常值者,大多是CIK输注或IFN-α治疗者,移植后予IFN-α或CIK细胞治疗能使患者TH1增高。TH2,68.29%患者显著高于正常,这种异常可持续至移植后1年以上,TH2正常仅见于IFN-α治疗者,IFN-α能使TH2显著下降(P=0.000)。(3)胸腺因子治疗病例其CD4+CD25+、CD4+CD69+细胞有增高倾向。结论:自体干细胞移植后多种免疫制剂联合治疗有助于提高细胞免疫功能,监测TH1/TH2能基本反映移植后患者免疫状态,但其对预后的评估及长期生存的影响尚需观察积累更多的资料。更多还原

【Abstract】 BACKGROUD & 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-hodgekin Lymphoma (NHL), 3 Hodgekin 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)-α 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-α 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-α treatment. Furthermore, IFN-α 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-α 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.更多还原