利妥昔单抗联合NK细胞治疗惰性B细胞淋巴瘤疗效分析

发布时间：2018-06-17 21:27

本文选题：惰性B细胞淋巴瘤 + 利妥昔单抗　；参考：《吉林大学》2015年硕士论文

【摘要】：背景：惰性B细胞淋巴瘤是一组恶性程度低、疾病进展缓慢的非霍奇金淋巴瘤，主要包括慢性淋巴细胞白血病/小淋巴细胞淋巴瘤（CLL/SLL）、1~2级滤泡性淋巴瘤（FL）、边缘区淋巴瘤（MZL）和淋巴浆细胞淋巴瘤等。利妥昔单抗是针对B细胞表面CD20抗原的人鼠嵌合型单克隆抗体，它的应用明显改善了惰性B细胞淋巴瘤的疗效，但部分惰性B细胞淋巴瘤弱表达CD20，对利妥昔单抗治疗反应差，同时部分患者发病年龄较大，不能耐受传统化疗带来的不良反应。自体NK细胞和新鲜冰冻血浆分别通过增强ADCC效应和CDC效应来提高利妥昔单抗的疗效，并且较化疗不良反应少，并发症少。目的：探讨利妥昔单抗联合自体NK细胞治疗惰性B细胞淋巴瘤的疗效，为应用非化疗手段治疗老年惰性B细胞淋巴瘤提供依据。方法：收集查阅我院自2011年开始应用利妥昔单抗联合自体NK细胞或血浆治疗惰性B细胞淋巴瘤的所有患者，记录患者的临床资料、治疗效果。同时与我院自2009年1月至2015年2月应用利妥昔单抗联合化疗治疗惰性B细胞淋巴瘤患者相关信息进行对比分析。结果：1、本研究共收集明确诊断惰性B细胞淋巴瘤45例。利妥昔单抗联合自体NK细胞治疗组(非化疗组)17例，利妥昔单抗联合化疗资料组(化疗组)28例。2组患者在病理类型及LDH水平存在显著性差异，而年龄、性别、KPS评分、疾病分期及疾病状态的水平均无显著差异。非化疗组患者初治时中位年龄为62岁，化疗组为56岁。 2、在非化疗组17例患者中，累及骨髓14例，伴外周血白细胞增高13例，CLL9例。1疗程后中位白细胞总数、淋巴细胞绝对值、淋巴细胞百分比分别下降85.0%、91.1%、20.7%，并且随着治疗疗程数的增加，白细胞总数、淋巴细胞绝对值、淋巴细胞百分比恢复至正常的比例逐渐增多，4疗程后恢复至正常比例分别为85.7%、85.7%和71.4%，均超过70%。7例伴有血小板（4例）或血红蛋白（5例）减少的患者，71.4%（5/7）经治疗后血小板或血红蛋白明显升高。4例伴有可观察靶病灶的患者，75.0%（3/4）经治疗后病灶消失或明显缩小。 3、非化疗组ORR为88.2%，CR率41.2%，中位随访12个月，中位PFS9个月。 4、非化疗组中，3疗程组在ORR和CR率上均大于≤3疗程组（100%vs80%，71.4%vs20%），但两者差异无显著性（P=0.485，0.058）。≤3疗程和3疗程患者的PFS分别为7（3~12）个月和16（5~51）个月，差异具有显著性（P=0.032）。 5、化疗组的ORR为69.2%、CR率为26.9%，中位PFS15个月，与非化疗组相比，，差异均无显著性（P=0.873）。 6、不良反应，非化疗组3~4级骨髓抑制发生率较化疗组少（0.0%vs42.6%），感染率也较低（23.5%vs53.6%），差异均有显著性（P分别为0.001和0.048）。结论： 1.非化疗组，1疗程后白细胞总数、淋巴细胞绝对值、淋巴细胞比例均获得显著迅速下降；并且随着疗程数增加，恢复至正常的比例明显增多，4疗程后均达到70%以上。 2.非化疗组，伴有血小板、血红蛋白减少的患者，利妥昔单抗联合自体NK细胞治疗后，71.5%明显升高；靶病灶明显缩小，有效率达75%。 3.对比分析，非化疗组的ORR、CR率分别为88.7%、41.2%，均高于化疗组的69.2%和26.9%。提示，利妥昔单抗联合自体NK细胞治疗至少可以获得与利妥昔单抗联合化疗相当的疗效。 4.进一步亚组分析，非化疗组，3疗程的PFS显著优于≤3疗程组。提示3疗程利妥昔单抗联合NK细胞治疗可以获得更好的远期疗效。 5.不良反应，非化疗组显著优于化疗组。提示，更适合不能耐受化疗的老年群体。 6.综上：本研究应用妥昔单抗联合自体NK细胞治疗惰性B细胞淋巴瘤，获得与利妥昔单抗联合化疗相当的疗效。而且，不良反应明显优于化疗组。提示，针对以老年人发病为主体的惰性B细胞淋巴瘤具有特殊的应用价值。
[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.
【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R733.1

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