本文選題：惰性B細胞淋巴瘤 + 利妥昔單抗��； 參考：《吉林大學》2015年碩士論文

【摘要】：背景：惰性B細胞淋巴瘤是一組惡性程度低、疾病進展緩慢的非霍奇金淋巴瘤，主要包括慢性淋巴細胞白血病/小淋巴細胞淋巴瘤（CLL/SLL）、1~2級濾泡性淋巴瘤（FL）、邊緣區(qū)淋巴瘤（MZL）和淋巴漿細胞淋巴瘤等。利妥昔單抗是針對B細胞表面CD20抗原的人鼠嵌合型單克隆抗體，它的應用明顯改善了惰性B細胞淋巴瘤的療效，但部分惰性B細胞淋巴瘤弱表達CD20，對利妥昔單抗治療反應差，同時部分患者發(fā)病年齡較大，不能耐受傳統(tǒng)化療帶來的不良反應。自體NK細胞和新鮮冰凍血漿分別通過增強ADCC效應和CDC效應來提高利妥昔單抗的療效，并且較化療不良反應少，并發(fā)癥少。 目的：探討利妥昔單抗聯(lián)合自體NK細胞治療惰性B細胞淋巴瘤的療效，為應用非化療手段治療老年惰性B細胞淋巴瘤提供依據(jù)。 方法：收集查閱我院自2011年開始應用利妥昔單抗聯(lián)合自體NK細胞或血漿治療惰性B細胞淋巴瘤的所有患者，記錄患者的臨床資料、治療效果。同時與我院自2009年1月至2015年2月應用利妥昔單抗聯(lián)合化療治療惰性B細胞淋巴瘤患者相關(guān)信息進行對比分析。 結(jié)果：1、本研究共收集明確診斷惰性B細胞淋巴瘤45例。利妥昔單抗聯(lián)合自體NK細胞治療組(非化療組)17例，利妥昔單抗聯(lián)合化療資料組(化療組)28例。2組患者在病理類型及LDH水平存在顯著性差異，而年齡、性別、KPS評分、疾病分期及疾病狀態(tài)的水平均無顯著差異。非化療組患者初治時中位年齡為62歲，化療組為56歲。 2、在非化療組17例患者中，累及骨髓14例，伴外周血白細胞增高13例，CLL9例。1療程后中位白細胞總數(shù)、淋巴細胞絕對值、淋巴細胞百分比分別下降85.0%、91.1%、20.7%，并且隨著治療療程數(shù)的增加，白細胞總數(shù)、淋巴細胞絕對值、淋巴細胞百分比恢復至正常的比例逐漸增多，4療程后恢復至正常比例分別為85.7%、85.7%和71.4%，均超過70%。7例伴有血小板（4例）或血紅蛋白（5例）減少的患者，71.4%（5/7）經(jīng)治療后血小板或血紅蛋白明顯升高。4例伴有可觀察靶病灶的患者，75.0%（3/4）經(jīng)治療后病灶消失或明顯縮小。 3、非化療組ORR為88.2%，CR率41.2%，中位隨訪12個月，中位PFS9個月。 4、非化療組中，3療程組在ORR和CR率上均大于≤3療程組（100%vs80%，71.4%vs20%），但兩者差異無顯著性（P=0.485，0.058）。≤3療程和3療程患者的PFS分別為7（3~12）個月和16（5~51）個月，差異具有顯著性（P=0.032）。 5、化療組的ORR為69.2%、CR率為26.9%，中位PFS15個月，與非化療組相比，，差異均無顯著性（P=0.873）。 6、不良反應，非化療組3~4級骨髓抑制發(fā)生率較化療組少（0.0%vs42.6%），感染率也較低（23.5%vs53.6%），差異均有顯著性（P分別為0.001和0.048）。 結(jié)論： 1.非化療組，1療程后白細胞總數(shù)、淋巴細胞絕對值、淋巴細胞比例均獲得顯著迅速下降；并且隨著療程數(shù)增加，恢復至正常的比例明顯增多，4療程后均達到70%以上。 2.非化療組，伴有血小板、血紅蛋白減少的患者，利妥昔單抗聯(lián)合自體NK細胞治療后，71.5%明顯升高；靶病灶明顯縮小，有效率達75%。 3.對比分析，非化療組的ORR、CR率分別為88.7%、41.2%，均高于化療組的69.2%和26.9%。提示，利妥昔單抗聯(lián)合自體NK細胞治療至少可以獲得與利妥昔單抗聯(lián)合化療相當?shù)寞熜А?4.進一步亞組分析，非化療組，3療程的PFS顯著優(yōu)于≤3療程組。提示3療程利妥昔單抗聯(lián)合NK細胞治療可以獲得更好的遠期療效。 5.不良反應，非化療組顯著優(yōu)于化療組。提示，更適合不能耐受化療的老年群體。 6.綜上：本研究應用妥昔單抗聯(lián)合自體NK細胞治療惰性B細胞淋巴瘤，獲得與利妥昔單抗聯(lián)合化療相當?shù)寞熜�。而且，不良反應明顯優(yōu)于化療組。提示，針對以老年人發(fā)病為主體的惰性B細胞淋巴瘤具有特殊的應用價值。
[Abstract]:Background: inert B cell lymphoma is a group of low malignancy and slow progression of non Hodgkin's lymphoma, including chronic lymphocytic leukemia / small lymphocyte lymphoma (CLL/SLL), 1~2 class follicular lymphoma (FL), marginal zone lymphoma (MZL) and lymphocytic lymphocytic lymphoma. Rituximab is aimed at CD20 on the surface of B cells. Antigen human mouse chimeric monoclonal antibody, its application significantly improved the efficacy of inert B cell lymphoma, but partial inert B cell lymphoma weakly expressed CD20 and had poor response to rituximab. At the same time, some patients were older, and were unable to tolerate the adverse reactions brought by traditional chemotherapy. Autologous NK cells and fresh frozen plasma were divided. Through enhanced ADCC and CDC effects to improve the efficacy of rituximab, and adverse reaction of chemotherapy and less complications.
Objective: To investigate the efficacy of rituximab combined with autologous NK cells in the treatment of inert B cell lymphoma, and to provide a basis for the treatment of elderly inert B cell lymphoma with non chemotherapy.
Methods: all patients with rituximab combined with autologous NK cell or plasma treatment for inert B cell lymphoma in 2011 were collected and consulted in our hospital. The clinical data and therapeutic effects of the patients were recorded and the related letters of rituximab combined with rituximab in our hospital from January 2009 to February 2015 were used to treat patients with inert B cell lymphoma. Interest rates were analyzed.
Results: 1, 45 cases of inert B cell lymphoma were diagnosed in this study. There were 17 cases of rituximab combined with autologous NK cell therapy group (non chemotherapy group). There were significant difference in pathological type and LDH level in group.2 of rituximab combined with chemotherapy group (chemotherapy group), and age, sex, KPS score, disease staging and disease status. There were no significant differences in the level of non chemotherapy group patients at a median age of 62 years, the chemotherapy group was 56 years old.
2, among the 17 patients in the non chemotherapy group, 14 cases were involved in bone marrow and 13 cases were associated with peripheral blood leukocyte increase. The total number of white blood cells, the absolute value of lymphocyte and the percentage of lymphocyte decreased by 85%, 91.1%, 20.7% after CLL9.1 course of treatment, and the total number of white blood cells, the absolute value of lymphocyte and the percentage of lymphocyte recovery were restored with the number of treatment courses. The proportion of the normal proportion increased gradually. After 4 courses, the normal proportion was 85.7%, 85.7% and 71.4%, respectively, more than 70%.7 patients with thrombocytopenia (4 cases) or hemoglobin (5 cases) decreased, 71.4% (5/7) after treatment, platelet or hemoglobin was significantly increased in.4 cases with target focus, 75% (3/4) disappeared after treatment. Or significantly reduced.
3, non chemotherapy group ORR was 88.2%, CR was 41.2%, the median follow-up was 12 months, median PFS9 months.
4, in the non chemotherapy group, the rate of ORR and CR in the 3 course group was greater than that of the 3 course group (100%vs80%, 71.4%vs20%), but there was no significant difference between the two groups (P=0.485,0.058). The PFS was 7 (3~12) months and 16 months (5~51) months in the 3 course of treatment and 3 course of treatment, and the difference was significant (P=0.032).
5, the chemotherapy group ORR was 69.2%, CR was 26.9%, the median PFS15 months, compared with the non chemotherapy group, there was no significant difference (P=0.873).
6, the incidence of 3~4 grade myelosuppression in non chemotherapy group was less than that in chemotherapy group (0.0%vs42.6%), and the infection rate was lower (23.5%vs53.6%), and the difference was significant (P was 0.001 and 0.048 respectively).
Conclusion:
1. in the non chemotherapy group, the total number of white blood cells, the absolute value of lymphocytes and the proportion of lymphocytes in the 1 course of treatment decreased significantly, and the proportion of the recovery to normal increased with the number of courses, and all reached more than 70% after the 4 course of treatment.
2. patients with non chemotherapy group, accompanied by thrombocytopenia and hemoglobin, after rituximab combined with autologous NK cells, 71.5% significantly increased; the target focus was significantly reduced and the effective rate was up to 75%.
3. contrast analysis, the rate of ORR, CR in non chemotherapy group was 88.7%, 41.2%, respectively, which was higher than that of chemotherapy group 69.2% and 26.9%.. Rituximab combined with autologous NK cell therapy could obtain at least the curative effect of combination with rituximab combined with chemotherapy.
4. further subgroup analysis, non chemotherapy group, the 3 course of PFS was significantly better than the 3 course of treatment. It was suggested that the 3 course of rituximab combined with NK cell therapy could obtain better long-term effect.
5. adverse reactions, non chemotherapy group was significantly better than the chemotherapy group. That is more suitable for the elderly can not tolerate chemotherapy.
6. comprehensive: This study used the combination of rituximab and autologous NK cells in the treatment of inert B cell lymphoma, which was quite effective with rituximab combined with chemotherapy. Moreover, the adverse reaction was obviously better than the chemotherapy group. It suggested that it has special application value for the inert B cell lymphoma, which is the main body of the elderly.
【學位授予單位】：吉林大學
【學位級別】：碩士
【學位授予年份】：2015
【分類號】：R733.1

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相關(guān)期刊論文 前2條

1 夏忠軍;王風華;黃慧強;駱卉妍;李宇紅;林桐榆;姜文奇;管忠震;;含美羅華方案治療B細胞性惰性淋巴瘤34例報告[J];癌癥;2006年04期

2 薛雯;王黎;趙艷;趙維蒞;;209例慢性B淋巴細胞增殖性疾病臨床特征及預后分析[J];臨床血液學雜志;2014年06期

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