A controlled trial of BCG immunotherapy in bronchogenic carcinoma treated by surgical resection

Summary Ninety-two patients with bronchogenic carcinoma who were treated by surgical resection of the tumour were subsequently given immunotherapy with BCG (Glaxo). The study was strictly randomised into three groups. Twenty-nine patients received multipuncture BCG (50–250×10⁶ viable units) and 26 patients intradermal BCG (0.4–0.9×10⁶ viable units) treatment being given at 1, 2, 5, 9, 13 and 26 weeks after operation and every 26 weeks thereafter. Thirty-seven control patients did not receive BCG. The patients have been observed for 15–33 months. There was no significant difference in survival between the control group and the two immunotherapy groups or between the two immunotherapy groups. The tumour cell type and presence of mediastinal nodes significantly influenced overall survival but not the response to BCG immunotherapy. The possible reasons for the failure of BCG to prolong survival in this study are discussed.     

Neoadjuvant PD-1 blockade plus chemotherapy versus chemotherapy alone in locally advanced stage II-III gastric cancer: A single-centre retrospective study

BackgroundPD-1 blockade has been shown to have promising efficacy and acceptable safety profiles in advanced and metastatic gastric cancer; however, the efficacy and safety of neoadjuvant PD-1 blockade-based immunotherapy plus chemotherapy in locally advanced gastric cancer (LAGC) remain uncertain.MethodsWe performed a retrospective review of patients with LAGC who received neoadjuvant treatment followed by D2 radical resection at the Affiliated Hospital of Qingdao University from 2019 to 2021. The primary aim was to investigate the difference in pathological response rates between neoadjuvant PD-1 immunotherapy plus chemotherapy and neoadjuvant chemotherapy alone. Multivariable models for pathological complete response (pCR) were constructed to investigate the factors that facilitate pCR. Trial registration: QYFYWZLL27406.ResultsA total of 77 patients were included in the analysis, among whom 34 (44.2%) received neoadjuvant PD-1 blockade immunotherapy plus chemotherapy. A higher pCR rate was observed in the neoadjuvant PD-1 blockade immunotherapy plus chemotherapy group (8 of 34, 23.5% vs. 2 of 43, 4.7%, P=0.019). Multivariate logistic regression analysis of pCR revealed neoadjuvant PD-1 blockade plus chemotherapy regimen promoted pCR (OR 12.95, P=0.016). Regarding safety, 76.5% (26 of 34) of patients in the PD-1 blockade plus chemotherapy group and 76.7% (33 of 43) of patients in the chemotherapy group experienced treatment-related adverse events (TRAEs), and grade 3 or worse adverse events were 29.4% (10 of 34) and 34.9% (15 of 43), respectively.ConclusionNeoadjuvant PD-1 blockade plus chemotherapy induced a higher pCR rate than neoadjuvant chemotherapy, and the combined therapy was tolerable in LAGC patients.     

Tumour-cell-induced production of tumour necrosis factor by monocytes of gastric cancer patients receiving BCG immunotherapy

Summary Human peripheral blood monocytes cocultured with tumour cells were used as an in vitro model of in situ interactions between tumour-infiltrating macrophages and the tumour. Tumour cells stimulated de novo expression of the human tumour necrosis factor (TNF) gene in monocytes and caused the release of TNF into the culture supernatant. A group of 14 patients with stage IVA gastric cancer receiving adjuvant chemotherapy (5-FU, Adriamycin, mitomycin C: FAM) or immunochemotherapy (BCG+FAM) was investigated for the ability of monocytes to produce TNF in vitro upon stimulation with tumour cells or purified protein derivative of tuberculin (PPD). Patients were followed at biweekly intervals, i.e. before each instillation of BCG epicutaneously over a period of 10 weeks. It was found that monocytes of some patients receiving BCG at the end of the observation period had an enhanced ability to produce TNF following stimulation with tumour cells. In contrast, such production was not substantially altered during the study period in patients on chemotherapy. PPD-induced TNF production was much weaker and was not significantly changed during this observation time. We infer that BCG immunotherapy may induce the subtle changes in some cancer patients that lead to an increased interaction between monocytes and tumour cells and result in enhanced production of cytokine(s) with antitumour properties.     

BCG in the immunotherapy of malignant lymphomas

Summary The effectiveness of a nonspecific immunostimulation in related human or animal diseases incited us to do a study of nonspecific immunotherapy by BCG in Hodgkin's disease, and then in other malignant lymphomas. Seventy patients, each one fulfilling at least 2 criteria of poor prognosis, were initially put in complete remission by a combination of radio-chemotherapy, followed by a reinforcing chemotherapy. These patients were then randomized into two groups. The first group received no further treatment; the second received BCG in weekly cutaneous scarifications. Eight patients were excluded from the study. The rate of relapses is significantly lower in the treated group. The results are discussed. Other therapeutic studies are necessary to fix the indications and modalities of this immunotherapy.Communication to the Medical Oncology Society, Nice, December 7, 1976     

Postoperative adjuvant immunotherapy of gastric cancer with BCG-cell wall skeleton

The clinical effectiveness of immunotherapy with the cell wall skeleton of Bacillus Calmette-Guérin was assessed in a study involving 140 consecutive patients with gastric cancer, who were gastrectomized at a single institution from January 1976 through December 1978. These patients were randomized by an envelope method after operation and divided into three treatment groups: 'control', 'chemotherapy', and 'chemotherapy plus immunotherapy with BCG-CWS.' Only two patients who died during surgery were excluded, and a survey of survival periods was made on the remaining 138 patients in January 1982. As a result, statistically significant differences in the survival rate curve were observed between the control and chemotherapy plus immunotherapy groups (P less than 0.01), and between the chemotherapy and chemotherapy plus immunotherapy groups (P less than 0.05). These results emphasize effectiveness of BCG-CWS as an adjuvant immunotherapeutic agent in gastrectomized cancer patients.     

Enhancement of defective monocyte function during immunotherapy with recombinant interferon

Summary The influence of immunotherapy with high dose (50×10⁶ units/m²) recombinant leukocyte A interferon on blood monocyte functions was studied in eight patients with bronchogenic carcinoma. Monocyte chemotactic responsiveness (MCR) was initially depressed (9.8±1.6 cells/field) compared to healthy controls (17.6±5.1 cells/field), P<0.01. Recombinant interferon was administered three times weekly, and after 7 days a significant improvement in chemotaxis was observed (16.6±3.0 cells/field), P<0.05. The MCR remained normal until cessation of interferon therapy (>1 month). Phagocytic and candidacidal activities were normal in the patients and were not influenced by treatment with interferon. In conclusion, high dose recombinant interferon given to cancer patients caused a normalization of defective blood monocyte chemotaxis, which persisted for >1 month.     

Cancer immunotherapy.

Important contributions that stimulated studies in cancer immunotherapy included: (1) the discovery of tumour-associated antigens; (2) the observation that infection with bacille Calmette-Guérin (BCG) in animals was protective against tumour challenge; and (3) the observation that immunodepression due either to malignant disease or to treatment of the disease, was, in some instances, related to prognosis. Immunotherapy trials with microbial agents have involved attempts to obtain a local effect by injecting the agent into the tumour or into the region of the tumour and to obtain a "systemic" effect distant from the site of injection. Trials with active specific immunotherapy involving tumour cells or tumour cell extracts have frequently involved the combination of these specific agents with a nonspecific adjuvant such as BCG. Recent studies with thymosin and levamisole in patients with lung cancer and other types of malignant disease have shown prolonged survival in the groups receiving immunotherapy.     

Results of randomized trials of immunotherapy for acute leukemia

Summary For more than a decade clinical trials have attempted to define the role of immunotherapy in the treatment of patients with acute leukemia. Based on animal studies which indicated that non-specific immune stimulation had an antitumor effect if the tumor burden was small, the use of immunotherapy during remission in patients with acute leukemia seemed appropriate following the initial report of the success of bacillus Calmette-Guerin (BCG) in prolonging remission duration and survival in acute lymphoblastic leukemia. Therefore a series of randomized clinical trials was initiated to confirm these original observations. In four studies comparing BCG inoculations, with or without allogeneic leukemia cells, and chemotherapy or no therapy, no advantage of immunotherapy was noted. Immunotherapy appeared to be equally as good as chemotherapy. A combination of BCG and chemotherapy showed some advantage in one study, but no advantage was noted in two other studies.In acute myeloblastic leukemia several randomized trials suggested that BCG or one of its derivatives when given alone, in combination with allogeneic cells, or with chemotherapy had a marginal effect in prolonging remission duration and survival when compared to chemotherapy or rno therapy.In conclusion, immunotherapy during remission has marginal activity in acute leukemia.     

Immunotherapy of breast cancer,malignant melanoma,and acute leukemia with BCG: Prolongation of disease free interval and survival

Summary Results of immunotherapy with BCG in patients with malignant melanoma, breast cancer, and acute leukemia are described. The first study demonstrated that high doses of living BCG organisms (6×10⁸ viable units) delivered by scarification in the upper arms and legs prolonged the disease-free interval and survival of 52 malignant melanoma patients with regional lymph node metastases compared to 218 comparable surgical control patients. Patients with trunk and extremity, but not head and neck melanoma, benefited from BCG, suggesting the importance of the delivery of BCG into the tumor-involved lymphatics.The second study evaluated the therapeutic efficacy of living BCG organisms by scarification in a group of adult acute leukemia patients after the cessation of chemotherapy. Thirty-seven patients had been in remission on intermittent chemotherapy for 12–24 months. Following late intensive consolidation chemotherapy, 7 consecutive patients received no further therapy and then 30 consecutive patients received BCG. Patients maintained on BCG have had a prolonged disease-free interval compared to those given on no further therapy (P=0.07) or compared to a group of similar patients maintained on chemotherapy alone (P=0.001). Similarly, the survival has been improved for patients maintained on BCG compared to those left unmaintained (P=0.009), or those maintained on chemotherapy (P=0.001).The principles of intermittent chemotherapy combined with BCG immunotherapy, first developed in patients with disseminated melanoma and acute myelogenous leukemia, have been confirmed in a series of patients with disseminated breast cancer. Forty-five patients treated with a combination of 5-FU, adriamycin, and cyclophosphamide (FAC) plus BCG by scarification showed prolongation of remission as well as survival compared to a comparable group of 44 patients treated with FAC chemotherapy without immunotherapy. Thus, 23/44 patients treated with FAC have died (median=14 months) compared to only 5/45 patients on FAC-BCG (median=12⁺ months), P=0.005. The limitations of BCG immunotherapy as well as speculations for future developments of immunotherapy are discussed.This work was supported by Contract No1-CB 33888 from the National Institutes of Health, Public Health Service, Bethesda, Maryland 20014. Drs. Gutterman and Mavligit are the recipients of Career Development Awards (Ca 71007-02 and CA 00130-01, respectively) from the National Institutes of Health, Education, and Welfare, Bethesda, Maryland 20014.     

参芪扶正注射液对急性淋巴细胞白血病化疗患者造血和免疫功能的影响

目的:观察参芪扶正注射液对急性淋巴细胞白血病化疗患者造血及免疫功能的影响。方法:收集96例处于初治诱导缓解治疗阶段的急性淋巴细胞白血病患者,并将其随机分为治疗组和对照组。治疗组48例患者在进行常规化疗的同时给予参芪扶正注射液250 m L,1次/天,共28天;对照组48例患者仅接受常规化疗,两组患者均给予相同的支持对症治疗。治疗结束后,观察两组患者的疾病缓解率、治疗前后造血系统、T和B淋巴细胞亚群的变化情况。结果:化疗结束后,治疗组患者的疾病缓解率为89.6%,对照组为83.3%,两组比较无统计学差异(P0.05);化疗14天及化疗结束后1周,治疗组患者的白细胞、红细胞计数和血红蛋白水平明显高于对照组(P0.05);且化疗结束后1周,治疗组患者的CD3+、CD4+及CD4+/CD8+含量均明显高于对照组(P0.05)。而两组患者治疗前后的血小板计数、CD3-CD19+含量比较均不具有统计学差异(P0.05)。结论:参芪扶正注射液辅助治疗不仅能够改善化疗所致的急性淋巴细胞白血病患者的骨髓抑制,而且能够提高其细胞免疫功能,有助于患者化疗后的恢复。     

Therapeutic outcomes of combining cryotherapy,chemotherapy and DC-CIK immunotherapy in the treatment of metastatic non-small cell lung cancer

Currently there are no effective therapies for the treatment of metastatic non-small cell lung cancer (NSCLC). Here, we conducted a retrospective study of 161 patients to evaluate the therapeutic effects of combining cryosurgery, chemotherapy and dendritic cell-activated cytokine-induced killer cells (DC-CIK) immunotherapy. The overall survival (OS) after diagnosis of metastatic NSCLC to patient death was assessed during a 5-years follow-up period. OS of patients who received comprehensive cryotherapy was (median OS, 20 months; n = 86) significantly longer than that of patients who did not received cryotherapy (median OS, 10 months; n = 75; P < 0.0001). Five treatment combinations were selected: chemotherapy (n = 44); chemo-immunotherapy (n = 31); cryo-chemotherapy (n = 32); cryo-immunotherapy (n = 21); and cryo-chemo-immunotherapy (n = 33). A combination of cryotherapy with either chemotherapy or immunotherapy lead to significantly longer OS (18 months and 17 months, respectively) compared to chemotherapy and chemo-immunotherapy (8.5 months and 12 months, respectively; P < 0.001); however, the median OS of patients who underwent cryo-chemo-immunotherapy was significantly longer (27 months) compared to the other treatment programs (P < 0.001). In conclusion, a combination of cryotherapy, chemotherapy and DC-CIK immunotherapy proved the best treatment option for metastatic NSCLC in this group of patients.     

Adjuvant BCG immunotherapy for stage I and II malignant melanoma.

Initial adjuvant immunotherapy trials have demonstrated a greater disease-free interval in patients treated with bacille Calmette-Guérin (BCG) compared with historical controls. In this study 149 patients at high risk of recurrence after surgical treatment of local or regional malignant melanoma were given BCG for 2 years and were followed up for a median of 28 months from the start of immunotherapy. The 36 patients in the comparison group had a higher rate of recurrence than the patients treated with BCG, and the rate in the treatment group was close to that reported from a similar study at the University of California at Los Angeles. The relatively long disease-free interval for the high-risk comparison patients in this study suggests that the control groups at other centres may have included patients with unrecognized additional risk. The rates of survival in the Canadian treatment group were also comparable to those reported by other centres. However, reports of a favourable BCG-mediated pattern of recurrence could not be confirmed. Therefore, the routine use of adjuvant BCG immunotherapy is not recommended.     

Adjuvant BCG immunotherapy for malignant melanoma.

A total of 199 patients with stage I malignant melanoma at Clark''s level 3 to 5 of invasion were entered into a prospectively controlled randomized clinical trial that attempted to assess the value of local and systemic immunotherapy with BCG (bacille Calmette-Guérin) after surgery. The patients were randomly assigned, with stratification by Clark''s level, to receive either routine follow-up or immunotherapy with BCG, administered intradermally with a Heaf gun around the site of wide excision and then given orally for 2 years. Intradermal administration of BCG was repeated after 1 year''s oral therapy with BCG. Of the 99 patients in the treatment group 66 had Clark''s level 3, 28 had level 4, and 5 had level 5 invasion. Of the 100 patients in the control group, 61 had level 3, 36 had level 4, and 3 had level 5 invasion. Other prognostic factors, such as sex, depth of invasion, histologic features, site of disease and type of surgery, were evenly distributed. There were 57 recurrences of the melanoma, 24 in the treatment group and 33 in the control group. However, this trend was not statistically significant (p = 0.194). The suggestion that BCG may reduce the likelihood of local/regional recurrence has not been confirmed with longer follow-up. There were 13 such recurrences in the BCG group, compared with 21 in the control group; the proportions of patients in each group who had such a recurrence were not significantly different. Of the 199 patients 41 died, 24 in the control group and 17 in the treatment group; again, this difference was not significant. While there may be minor activity in selected patients, there appeared to be no benefit from this form of adjuvant BCG therapy in patients with malignant melanoma.     

Regional immunotherapy has a detrimental effect on the response to combined irradiation and chemotherapy in locally advanced non-small cell bronchogenic carcinoma

Summary Twenty-one patients with stage III M₀ non-oat cell bronchogenic carcinoma confined to the thorax were randomized to receive either intrapleural BCG (10⁷ cfu, Tice strain) or intrapleural saline 3 weeks prior to beginning combined irradiation and chemotherapy. Radiation to the primary tumor and regional nodes was given at a dose of 3,000 rad in ten sessions and was followed in 7–14 days by CAMP chemotherapy (cyclophosphamide, adriamycin, methotrexate, and procarbazine) for a planned duration of 6 months. Isoniazid, 300 mg/day, was given to all patients for 3 months starting 1 week after intrapleural therapy. There were no significant differences in pretreatment prognostic factors or in response to radiation therapy. The patients receiving intrapleural BCG in addition to radiation and chemotherapy had a median survival of 18 weeks, significantly shorter than that for the patients receiving intrapleural saline (54 weeks, P=0.017).Presented in part at the 16th Annual Meeting of the American Society of Clinical Oncology, San Diego, California, May 27, 1980     

Various uses of BCG and allogeneic acute leukemia cells to treat patients with acute myelogenous leukemia

Summary Ninety-six remission patients with acute myelogenous leukemia have been treated with various forms of immunotherapy and chemotherapy in three distinct studies and the clinical outcome of these patients has been reported. In the first study 22 patients were maintained on chemotherapy alone and 28 patients were given the same chemotherapy and additional immunotherapy consisting of BCG and irradiated allogeneic AML cells given at separate sites weekly. It was found that there was a significant increase in survival time of the patients who received immunotherapy (median 510 days) compared with the chemotherapy alone patients (270 days). The p value for this was 0.03. The reason for this prolongation of survival was mainly due to a markedly increased survival time of immunotherapy patients after they relapsed when compared with the chemotherapy patients (165 days compared with 75 days median, p equal to 0.0005). In the second sequential study 24 patients were given immunotherapy alone consisting of irradiated allogeneic AML cells and BCG given at separate sites, and this was compared with unirradiated allogeneic cells and BCG given to 22 patients. There was no difference in the remission length or survival between these two groups. In the third study 13 patients received irradiated cells and BCG as in Study 1 and a further 11 patients received the same immunotherapy but also received a mixture of cells and BCG given during the first three months. There was no difference in the remission and survival of these two groups. The significance of these results is discussed.     

1975 current results of the first 100 cytologically typed acute lymphoid leukemia submitted to BCG active immunotherapy

Summary The first 100 acute lymphoid (and undifferentiated) leukemias, (of which the smears at the first presentation of the disease are still available for typing), treated successively with remission induction chemotherapy, complementary cell-reducing chemoradiotherapy and then active immunotherapy with irradiated pooled allogeneic leukemic cells and fresh Pasteur Institute BCG applied on scarifications, have been reviewed, especially in connection with BCG application.Tolerance of BCG has been good. Its application had to be stopped due to a side effect (choroiditis) in only one patient. This toxic cost is negligible compared to that of so-called maintenance chemotherapy.No subject of our first control trial started in 1963 has relapsed between 3 and 13 years.In the overall group of the 100 patients studied, no relapse has been observed after 48 months, which is quite different to the observations of frequent relapses after that time in patients submitted to maintenance chemotherapy.Moreover, second remissions are obtained in 94% of the patients who relapsed early under immunotherapy, and their life expectancy after a second remission is as high as it is after the first remission.The median of survival is longer than 5 years.The action of active immunotherapy on the immune machinery has been followed by several assays, of which the increase of null cells (which include K-cells) may be the most interesting.Several prognostic factors have been demonstrated among which are sex, the volume of the neoplasia, meningeal localizations, and the cytological types. Age has no prognostic value in immunotherapy patients, contrary to maintenance chemotherapy patients. Also the cytological types behave differently under immunotherapy and under maintenance chemotherapy. The disease-free survival of more than 85% of the microlymphoblastic patients submitted to immunotherapy is not observed in J. Bernard's patients submitted to maintenance chemotherapy, which suggests that this high cure rate is due to active immunotherapy. Hence, these prognostic factors are probably factors of sensitivity to active immunotherapy. A statistical computerized study has shown that there is a link between the cytological types and other prognostic factors and that they all depend on the cytological type.Hence, our present protocol is adapted to this immunotherapy sensitivity factor. It comprises a nonrisk preimmunotherapy chemotherapy for the microlymphoblastic type, and a longer and more intensive chemotherapy for less immunotherapy sensitive types.     

Adjuvant immunotherapy in acute nonlymphocytic leukemia

Summary Of 112 patients (maximum age 70 years) with acute nonlymphocytic leukemia, 62 (55%) went into remission on an induction therapy of cytosine arabinoside and daunorubicin. 20 patients were randomized for maintenance treatment consisting of chemotherapy only and 22 patients for combined chemo-immunotherapy. The chemotherapy consisted in 5-day courses of daunorubicin and cytosine arabinoside and of thioguanine and cytosine arabinoside, alternating every month. The chemo-immunotherapy group also received weekly intracutaneous injections of 10⁹ allogeneic nonirradiated leukemic myeloblasts and 10⁶ BCG organisms (Glaxo) by Heaf gun.The median duration of the first remission was 164 days for the chemotherapy group and 464 days for the chemo-immunotherapy group. The corresponding median times of survival were 344 days for the first group and 734 days for the second group. The difference concerning median duration of survival is statistically significant. Thus immunotherapy seems to prolong survival.     

Immunotherapy of lung cancer with Corynebacterium parvum

Summary Thirty-one patients with inoperable carcinoma of the lung, excluding oat-cell carcinoma, were randomized to receive either chemotherapy alone, with methyl CCNU and vinblastine every 6–8 weeks (15 Pts) or such chemotherapy plus immunotherapy with IV infusions of Corynebacterium parvum (16 Pts). Prior duration of the disease was longer, and more patients had received previous therapy, in the immunotherapy group; these groups were otherwise very similar. In vitro lymphocyte response to phytohemagglutinin did not change significantly in either group, but the weaker response to Varidase declined in both groups after chemotherapy. An increased baseline level of circulating B lymphocytes was sharply reduced in the C. parvum group. There were no differences in -globulins or delayed skin test responses between immunotherapy and control patients at entry into this study or on follow-up. Median survival from entry was longer in the immunotherapy group (6 months) than in the control group (3 months), but this difference was not statistically significant and only two patients in each group lived for more than 11 months. It is conceivable that more benefit from C. parvum might have been recorded had more effective chemotherapy been available.     

A randomized trial of chemoimmunotherapy of acute nonlymphocytic leukemia in adults using a protein-bound polysaccharide preparation

Summary The effect of immunotherapy with a protein-bound polysaccharide preparation termed PSK on remission duration and survival of adults with acute nonlymphocytic leukemia (ANLL) was studied in a prospective randomized cooperative trial. After having achieved complete remission and receiving a consolidation therapy, 73 patients were randomized either to maintenance chemotherapy or to maintenance chemotherapy plus immunotherapy with PSK. Ultimately 36 patients in the chemotherapy group and 31 in the chemoimmunotherapy group were evaluable. Six months after the last entry, immunotherapy with PSK showed a borderline beneficial effect on remission duration (P=0.089) and on duration of survival (P=0.062). When the data were analyzed 12, 18, and 24 months after the last entry there were no significant differences in duration of remission and survival between the two groups. However, analysis of the data of patients who had maintained complete remission for more than 270 days revealed that immunotherapy had a suggestive beneficial effect (P=0.105), prolonging the 50% remission period by 418 days (885 vs 467 days). Thus, immunotherapy with PSK seems to be active in the treatment of adult ANLL when used for maintenance therapy in combination with chemotherapy, especially in patients with a good prognosis.     

DCs-CIK细胞免疫治疗联合化疗治疗晚期非小细胞肺癌的疗效观察

目的:探讨树突状细胞(DCs)和细胞因子诱导的杀伤(CIK)细胞免疫治疗联合化疗对晚期非小细胞肺癌患者的治疗效果。方法:将我院2012年2月到2014年2月就诊的72例晚期非小细胞肺癌患者随机分为对照组(n=36,单纯化疗组)和实验组(n=36,DCs-CIK细胞免疫联合化疗组)。比较两组患者治疗后的疗效、治疗前后免疫功能,并运用Kamofsky(KPS)评分来评估两组患者治疗后生活质量的改善情况。结果:实验组的疾病控制率(DCR)77.78%显著高于对照组的52.78%(P0.05)。治疗后实验组患者外周血CD3+、CD8+及NK细胞所占的比值较治疗前均上升显著(P0.05);治疗后对照组患者外周血CD3+、CD8+及NK细胞所占的比值较治疗前下降显著(P0.05)。治疗后实验组KPS评分提高率明显高于对照组(P0.05)。结论:DCs-CIK细胞免疫联合化疗能够提高晚期非小细胞肺癌患者的DCR,且显著改善患者的免疫功能和生活质量。