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Submitted:2019年9月16日|得到正式认可的：2019年9月26日|出版:2019年9月27日
如何引用本文：Emeraude NC，Saint-Cyr Sylvestre PD，Clotaire ND，Sarah B，Ismael K等。黑人非洲慢性淋巴白血病的化学疗法的结果：科特迪瓦的经验。Arch Cancer Sci Ther。2019;3：045-048。
doi：10.29328/journal.acst.1001008
版权许可证：©2019 Emeraude NC等。这是根据Creativ金博宝app体育e Commons归因许可分发的开放访问文章，该文章允许在任何媒介中不受限制地使用，分发和复制，前提是适当地引用了原始作品。
Keywords:慢性淋巴白血病；多化化学疗法；黑色非洲
黑人非洲慢性淋巴白血病的化学疗法的结果：科特迪瓦的经验
n’dhatz comoe emeraude1, Packo Dieu-le-veut Saint-Cyr Sylvestre1*，Nanho Danho Clotaie1，Bognini Sarah2, Kamara Ismael1，Boidy Kouakou1and Koffi Kouassi Gustave1
1科特迪瓦（Côted'Ivoire
2Department of Clinical Biology, University of “Felix Houphouet Boigny”, Abidjan, Côte d’Ivoire
*Address for Correspondence:Packo Dieu-le-le-deveut博士SAINT-CYR SYLVESTRE，临床血液学系“ Felix Houphouet Boigny”，Abidjan（Côted'Ivoire），P.O。Box 1439，Abidjan 04，Cote d’Ivoire，电话：0022589542209;电子邮件：stcyrpacko@yahoo.fr
Background:目前，慢性淋巴白血病的治疗使用新闻药物在我们国家更昂贵。原因，化学疗法的结果仍然是我们部门的挑战。
一种ims:To evaluate the place of polychemotherapy in the treatment of chronic lymphoid leukemia in black Africa.
Methods:It was a prospective, descriptive, analytic and non-comparative study, concerning the records of patients with chronic lymphoid leukemia treated and followed at the department of clinical hematology in Abidjan.
结果：We included 56 patients. The average age was 62 years with extremes of 38 and 84 years. The sex ratio was 0.8 in favor of female. The clinical signs noted a tumor syndrome among which splenomegaly, classified stage III (46, 43%) and adenopathy (64, 29%). Biologically, we observed a blood lymphocytosis (50%), an anemia (39.29%) and a thrombocytopenia (62.50%). The majority of patients were classified stage A of BINET (51.79%). The COP protocol (44.64%) and the monochemotherapy with chlorambucil (39.29%) were the most used. The therapeutic response of polychemotherapy was low (12.5%) compared to 35, 71% for monochemotherapy (p = 0.0001) with overall survival significantly better in monochemotherapy. The outcome of patients used polychemotherapy were more adverse that of patients used chlorambucil alone (p = 0,003). The overall probability of survival at 12 months was 90, 9% for patients who used monochemotherapy and 63, 4% for polychemotherapy.
Conclusion:Polychemotherapy in chronic lymphoid leukemia of black African has an adverse therapeutic response hence the interest of using new therapeutic possibilities.
慢性淋巴白血病（CLL）是西方国家最常见的白血病[1]。诊断期间患者的中位数为64岁，10％的患者在50岁之前被诊断出[1,2]。这种疾病的预后是异质的，因为一些患者在诊断后两年死亡，而另一些患者则存活了20多年，并且死于与非疾病相关的原因[3]。关于治疗，根据国家癌症研究所（NCI）的建议，多化学疗法在BINET B或C阶段的B或C阶段保持扩展，并在BINET的初始形式A的B或难治形式[4] [4]。此外，在CLL期间观察到的治疗进展是通过发现新闻治疗剂（例如氟达拉滨，单克隆抗体和嘌呤衍生物）的标志性的。但是，自从科特迪瓦（Côted'Ivoire）血液学系开设以来，选择单化学疗法和多化学疗法的使用仍有多元化，有时会引起争议[5]。这项研究的目的是评估多化化学疗法在治疗黑人非洲受试者CLL中的位置，并确定其治疗和进化特征。
这是一项回顾性，描述性，分析性和非舒张性研究，持续了两年（从2017年8月到2019年9月），在阿比贾（Abidjan）的临床血液学系进行了。这项研究涉及在此期间接受治疗和遵循的黑人非洲患者的档案。我们的研究中包括56名患者。招聘是系统的随机。使用准备和标准化的调查表收集数据。研究的参数是流行病学，临床，生物学和治疗性的。治疗方法的参数涉及使用CHOP，COP或Chlorambucil方案进行治疗的患者，该患者根据知名度和以下管理方式：
切碎协议：Cyclophosphamide: 750 mg/m2, IV day 1
H = Doxorubicine: 50 mg/m2, IV day1
Oncovin® ou Vincritine: 1,4 mg/m2, IV day 1
泼尼松：40 mg/m2每OS第1天到第5天
第1天=第21天
COP protocol:Cyclophosphamide: 300 mg/m2, IV day 1
Oncovin® ou Vincritine: 1,4 mg/m2，第1天
Prednisone: 60 mg/m2，第1天到第5天
第1天=第21天
氯辅协议：氯化木0,1 mg/kg连续。
对于COP或CHOP方案，治疗循环的总数为6或8个循环，而氯化木板方案的12个周期为12个周期。至于治疗反应，我们将完整的反应定义为临床体征的消失和大于4G/L血液淋巴细胞的数量。部分反应定义为减少肿瘤和淋巴细胞增多的50％。进展疾病涉及增加肿瘤综合征和淋巴细胞增多超过50％。这项研究是根据所有适用的动物护理，福利和使用的机构道德准则进行的。
Data entry and statistical analyses
Data analysis was performed using EPI-INFO 6.04b software at the significance level of 5%. The independence and percentage comparison tests were performed using the chi-square test (X²). The calculation of survival was done according to the Kaplan-Meir method, taking into account the different prognostic factors. The comparison of the survival curves was made using “log-rank” test.
Our sample was constituted of 56 patients. The tables 1 and 2 summarize respectively the descriptive characteristic and Therapeutical protocol, Therapeutical responses and Outcome of patients. As for the table 3, it shows the analytical characteristic of therapeutical responses of patients. The figure 1 gives the overall survival curve of patient.
| 表格1: Descriptive characteristic. | |
| Variables | Numbers（％） |
| 流行病学数据 | |
| 一种ges (years): average and extremes 62 [38 and 84] | |
| 38-59 | 32（57,14） |
| 60-84 | 24（42,85） |
| 性别 | |
| 女性 | 31（55,36） |
| 男性 | 25（44,64） |
| Clinical manifestations | |
| 性能状态 | |
| 0-2 | 48（14,28） |
| 3-4 | 8（85,72） |
| >Tumor syndrome | |
| 脾肿大（黑客阶段） | |
| 1-2 3 4-5 |
13（23,22） 26（46,43） 17（30,35） |
| 淋巴结肿大 | 36（64,29） |
| 生物表现形式 | |
| 血液淋巴细胞增多 | |
| < 75 75-80 > 80 |
10（17,86） 18 (32,14) 28（50） |
| 血红蛋白水平（G/DL） | |
| <10 > 10 |
22（39,29） 34 (60,71) |
| 血小板水平（g/l） | |
| <150 ≥150 |
35 (62,50) 21(37,50) |
| BINET柱子 | |
| 一种 B and C |
29（51,79） 27（48,21） |
| Table 2:患者的治疗方案，治疗反应和结果 | |
| Variables | Numbers (%) |
| 治疗方案 | |
| 劈 | 9（16,07） |
| COP | 25（44,64） |
| 氯buc | 22（39,29） |
| 治疗反应 | |
| 完全回应 | 27（48,21） |
| Partial response | 20 (35,71) |
| 进行性疾病 | 7 (12,5) |
| 结果 | |
| 生活和治疗 | 15（26,78） |
| 失去了跟进 | 22（39,28） |
| 死的 | 19 (39,92) |
| 表3: Analytical characteristic of therapeutical responses of patients. | |||
| 切碎/警察 | 氯buc | p | |
| Numbers (%) | Numbers (%) | ||
| RP | 20 (35,71) | 3（5,35） | 0,001 |
| cr | 7 (12,5) | 15（35，71） | |
| PD | 7 (12,5) | 4（7,14） | |
| 生活和治疗 | 17（50） | 20(90,90) | 0,003 |
| Death | 17（50） | 2(9,10) | |
图1：Overral survival curve.
我们的研究具有前瞻性，描述性，分析性和非态度。它涉及2017年8月至2019年9月期间的黑人非洲人患有CCL的患者。它旨在评估多化学疗法在CCL治疗中的地位。本研究表明，CLL是与文献数据相似的老年受试者的病理[1]。我们注意到女性的比例为0,8。Halker等。和Bastin等。分别观察到性别比2和1,4，有利于男性[6,7]。我们的研究的这些差异可以用样本的大小来解释。在临床上，血液淋巴细胞增多（23，21％）和脾肿大（39％，29％）是最常见的，我们的数据与Merle等人的数据相似。[8]。 The African literature showed that, CCL of African black is very tumoral and this seems to be related to a consultation delay [9,10]. The disease has a slow and chronic course; patients can live for ten years or can have a relatively normal life. Indeed in our study, the majority of our patients had a good general condition (85, 7%). Our results were identical of Koffi, et al. [9]. Lymphadenopathy were present clinically in 35.71% of cases, and defined the features of CCL of African black which splenomegaly is more predominate than lymphadenopathy. These data were found by all the previous studies [8-10]. Biologically, blood lymphocytosis was variable from one patient to another with a lymphocyte count of up to 200 G/L according to Merle, et al. [8]. Anemia is usually related to bone marrow failure. But it can be due to autoimmune hemolytic or an erythroblastopenia The majority of our patients were stage A of BINET (51.79%), similar to the study of Koffi, et al. and Ayemou, et al. [5,9]. Stage A of BINET is attributed to the independent factor of mortality and associated with a good factor. Indeed, the prognosis of the disease is a factor impacting the clinical, biological characteristics, the treatment, the therapeutic responses and the survival of the patients in our environment in Africa. Polychemotherapy was performed in 34 patients and 22 patients were treated by mono chemotherapy including chlorambucil. The choice of our treatment related to the stage of BINET, the presence of comorbidity and the financial means of patients. Apart from these conventional therapeutic protocols, the treatment of CLL has been disrupted since the discovery of new molecules such as monoclonal antibodies and fludarabine. These news drugs are used in particular during the advanced stages B and C and the emergence of refractory forms. Indeed, these news therapeutic molecules are available in Africa in our hospitals but inaccessible for the majority of our patients because of high cost. Thus conventional chemotherapy remains the only therapeutic alternative for the management of our patients. Therapeutically, 51.79% of our patients were CR while 48.21% had PR. We noted 33.92% of deaths, 39.29% of cases alive and 26.79% of Lost to follow-up. The CCL remains primarily an incurable disease, which can be cured at the cost of an allogeneic hematopoetic sterm cell graft. But, the age restricts this indication. Nowadays, the evaluation of the therapeutic response uses classical criteria of Complete Response (CR), Partial Response and Progressive Disease, but also phenotypic and medullar remission. The quality of the CR is evaluated by PCR on the Ig heavy chain genes and seems to be an essential factor of the prognosis after therapeutic intensification. Such explorations are inaccessible in our exercise condition, so that CR remains purely clinical and long-term, anecdotal RC. The analytical characteristic showed in our study that therapeutic response rates with polychemotherapy was worse comparated to the results of monochemotherapy. Our results were similar to the study of Lepetre, et al. [10]. Another meta-analysis study involving 2,000 patients from 10 trials confirms the efficacy of chlorambucil compared to combinations with ± doxorubicin alkylating agents [11,12]. However, the study of Leblond, et al. had showed that monochemotherapy by chlorambucil give worse results with less 10% of CR [13]. These differences could be explained by the indication of use of chemotherapy during CCL. Endeed, the polychemotherapy protocol in CLL applies to advanced stage of BINET B and C where complications are already established, unlike the monochemotherapy which is used at an early stage of the disease with a patient in good general state. In the CCL-80 and CCL-85 protocols, using polychemotherapy protocols, 60% response rates in advanced stages B were higher than that in our study [14]. However, in no study, this difference in efficacy has resulted in an increase in survival. The efficacy in terms of survival of the monochemotherapy on multidrug therapy observed during our study was confirmed by Jaksi, et al. using high doses of chlorambucil (10 mg/m²/day) until the RC [15].
The authors welcome the collaboration the team of department of clinical hematology of Yopougon Teaching Hospital for their contribution during the management of these patients.
资金
这项研究没有资助，也没有个人或财务关系，可能会对写作产生不当的影响。它是作者专业活动的一部分。这些作者受Yopougon教学医院临床血液学系的监督。
作者的贡献
The idea of this study was provided from Koffi Kouassi Gustave. He designed Drs N’dhatz Comoe Emeraude and Packo Dieu-le-veut Saint-cyr Sylvestre as a main investigator and proceeded to the selection of case, the interview, the documentary research and the writing of the manuscript. Professor Nanho Danho Clotaire, Drs. Kamara Ismael, Bognini Sarah and Boidy Kouakou revised the manuscript and provided additional information to enrich it. Koffi Kouassi supervised the study and did the final correction. All authors have read and approved the final version of the manuscript.
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