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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。
BACKGROUND & OBJECTIVE: Large-dose chemotherapy combined with autologous hematopoietic stem cell transplantation (AHSCT) has made great progress in the treatment of chemotherapy-sensitive tumors, but the recurrence rate is still high. Effective post-transplantation immune reconstruction may reduce recurrence. Therefore, after AHSCT patients, A variety of immunological preparations were used for combination therapy, and immune function monitoring was performed to evaluate the effects of various immune preparations on immune function. The rule of immune reconstitution after AHSCT and the feasibility of immunotherapy were preliminarily explored. METHODS: Twenty-four cases of relapse within 2 months or after transplantation were selected. Among them, 19 cases were non-Hodgkin’s lymphoma (NHL), 3 cases were Hodgkin’s lymphoma (HD), and 2 cases were adolescent rhabdomyosarcoma. IL-2 combined with IFN-α treatment, 6 patients were treated with thymic factors and CIK cells. Results: The median follow-up period was 12 months (2 to 60 months) with a sustained CR of 75.0%. The immune parameters were changed as follows: (1) Lymphocyte subsets: CD4+ T cells [healthy control (33.5 ± 6.9)%] began to decline significantly over 1 month after transplantation, and about 2.5% to 13.0% at 2 months ( The median was 5.6%), and gradually recovered thereafter. At 7 months, it was only 10.0% to 20.0%. After 1 year, all patients were still below normal, and the CD4/CD8 ratio continued to be inverted. B cells began to decline in more than one month after transplantation, and returned to normal at 4 months; however, cases treated with meropenh before transplantation were still 0 and 1% in the first half and 1 year after transplantation. The proportion of NK cells was approximately 10.0% to 20.0% at 2 months after transplantation (slightly higher than the normal value), and gradually decreased to normal thereafter. (2) T cell cytokine secretion: TH1, 48.79% of patients are below or at a normal low value; at normal values, most of them are CIK infusion or IFN-α therapy, and can be treated with IFN-α or CIK cells after transplantation. Increase the patient’s TH1. TH2, 68.29% of patients were significantly higher than normal, this abnormality continued to be more than 1 year after transplantation, TH2 normal only seen in IFN-α treatment, IFN-α can make TH2 decreased significantly (P=0.000). (3) The CD4+CD25+ and CD4+CD69+ cells tend to increase in cases of thymic factor treatment. Conclusion: Combination of multiple immunogenic agents after autologous stem cell transplantation is helpful to improve cellular immune function. Monitoring TH1/TH2 energy basically reflects the immune status of patients after transplantation, but its effect on the assessment of prognosis and long-term survival need to be observed more data of.