课题一 成人Ph阴性急性淋巴细胞白血病的优化治疗 课题二 卡泊芬净对急性白血病患者未分类真菌感染的危险度分层治疗
发布时间：2018-11-03 06:34
【摘要】：研究背景:Ph阴性急性淋巴细胞白血病(ALL)是一种异质性较高的急性白血病,国际上尚无统一的治疗方案,疗效参差不齐;同时化疗方案对不同年龄段患者的疗效也存在一定的差异。传统成人ALL化疗方案对整体生存的改善已十分有限,反观儿童ALL,却取得了较好的远期疗效。因此国际上越来越多的中心尝试应用儿童ALL方案治疗成人Ph阴性ALL,并取得了一定的成效。研究目的:比较传统成人Ph阴性ALL治疗方案和借鉴儿童ALL的新方案在疗效及安全性上的差异,并进一步分析这两种化疗方案对不同年龄段患者疗效的差异。研究方法:回顾性分析2009年1月4日至2013年9月4日收治的144例初治Ph阴性ALL患者资料,根据治疗方案分为传统的成人方案(方案1)组和借鉴儿童ALL的新化疗方案(方案2)组,分析其整体及不同分组条件下的疗效(完全缓解率、总生存、无复发生存)及安全性。研究结果:144例初治成人Ph阴性ALL患者接受化疗后,总完全缓解(CR)率为95.8%,1个疗程CR率为92.4%,5年总生存(OS)率为59.0%,5年无复发生存(RFS)率为48.6%。其中方案1组和方案2组在CR率(95.6%和96.1%,P=0.783)、3年OS率(65.3%和 63.4%,P=0.885)和 3 年 RFS 率(56.0%和 50.0%,P=0.931)差异均无统计学意义。方案1组中,14～30岁患者的OS要明显优于31～60岁患者(3年OS率69.6%:54.7%,P=0.042),RF5差异则无统计学意义(3年RFS率56.5%:57.0%,P=0.472)。方案2组中,14～30岁患者与31～60岁患者在OS及RFS上差异均无统计学意义(3 年 OS 率 65.7%:60.3%,P=0.423;3 年 RFS 率 51.5%:46.6%,P=0.655)。两组化疗方案在呼吸衰竭、心功能不全、真菌感染及肠梗阻发生率上差异均无统计学意义,方案1组的肾功能不全发生率要低于方案2组(P=0.011),菌血症发生率高于方案2组(P=0.000)。结论:两套成人ALL化疗方案耐受性较好,具有较高的CR率及长期生存率;同时,高龄(31～60岁)Ph阴性ALL患者有可能从非骨髓抑制药物含量高、化疗强度低的方案2中受益。研究背景:急性白血病患者中在化疗过程中约有5-10%的患者会发生侵袭性真菌感染,一旦发生感染,这部分患者的死亡率往往高达30-90%。因此,为了降低急性白血病患者在化疗过程中侵袭性真菌感染的发生率、降低真菌感染相关死亡率,安全有效的预防措施是否必要。急性白血病患者在化疗中往往合并有较多的脏器功能异常,因此,真菌感染预防治疗的疗效及安全性同样重要。既往文献报道显示,卡泊芬净在治疗侵袭性真菌感染时具有较好的疗效及安全性[1-3],是患者化疗期间较为理想的预防药物。考虑到费用及患者依从因素,抗真菌预防过程中,卡泊芬净初始治疗后经常序贯以伏立康唑片维持治疗。预防治疗中,除了疗效及安全性问题外,初始治疗中,卡泊芬净疗程的长短对患者疗效的影响尚无相关报道。研究目的:分析急性白血病患者中未分类真菌感染在不同危险度分层下,卡泊芬净疗程的长短对患者反应率的影响,并评价不同危险度分层下,患者生存率的差异。研究方法:回顾性分析2010年4月-2013年3月收治的141例伴有未分类真菌感染的急性白血病患者病例资料,所有患者均接受卡泊芬净静脉输注为初始治疗,并以伏立康唑口服为序贯治疗。按照真菌感染的危险度分组分为2组(标危组和高危组),每一组按照卡泊芬净疗程再分为2组(1周组和2周组),对比不同危险度分层下,不同疗程的卡泊芬净治疗后总反应率的差异;对比不同危险度分组下患者生存的差异。研究结果:患者治疗后整体反应率达75.9%,标危组患者在治疗第2周和第4周评价疗效时,1周卡泊芬净组和2周卡泊芬净组总反应率无明显差异(P=0.12和P=0.19);高危组患者在治疗第2周和第4周评价疗效时,2周卡泊芬净组的总反应率均明显高于1周卡泊芬净组(P=0.01和P=0.02)。结论:治疗急性白血病未分类真菌感染时,需按照真菌感染的危险度分组选择合适的卡泊芬净疗程,高危组患者选择卡泊芬净作为初始治疗时,疗程应达2周,而低危组患者疗程1周的卡泊芬净即可达到要求。
[Abstract]:Background: Ph-negative acute lymphoblastic leukemia (ALL) is a kind of acute leukemia with high heterogeneity, there is no unified treatment plan internationally, the curative effect is uneven, and the effect of chemotherapy regimen on patients with different age groups also has certain difference. The improvement of the overall survival of traditional adult ALL chemotherapy has been very limited, but it has achieved good long-term curative effect. Therefore, more and more centers in the world have tried to treat adult Ph-negative ALL with children's ALL regimen and have achieved some results. Objective: To compare the difference between the efficacy and safety of traditional adult Ph-negative ALL treatment protocol and the new protocol for children's ALL, and to further analyze the difference between the two chemotherapy regimens on the efficacy of patients with different age groups. Methods: The data of 144 patients with Ph-negative ALL treated from Jan. 4, 2009 to Sep. 4, 2013 were retrospectively analyzed. According to the treatment plan, we divided into two groups: the traditional adult protocol (protocol 1) group and the new chemotherapy regimen for reference to childhood ALL (Scheme 2). The efficacy (complete remission rate, total survival, non-recurrence survival) and safety of the whole group were analyzed. Results: In 144 patients with Ph-negative ALL treated with chemotherapy, the overall response rate (CR) was 95.8%, the CR rate was 92.4%, the total survival (OS) rate was 59. 0% in 5 years, and the rate of non-recurrent survival (RFS) in 5 years was 48. 6%. There was no significant difference in CR rate (95. 6% and 96.1%, P = 0. 783), OS rate (65. 3% and 63. 4%, P = 0. 885) and 3-year RFS rate (56. 0% and 50. 0%, P = 0. 931) in group 1 and group 2. In group 1, the OS of patients aged 14 ~ 30 years was significantly better than those of 31 ~ 60 years old (63.6%: 54. 7%, P = 0. 7). The difference of RF5 was not statistically significant (3years RFS rate was 56. 5%: 57. 0%, P = 0. 472). In group 2, there was no significant difference in OS and RFS between 14 ~ 30 years old and 31 ~ 60 years of age (3-year OS rate was 65. 7%: 60. 3%, P = 0.423; 3 years RFS rate 51. 5%: 46. 6%, P = 0.0655). There was no significant difference in the incidence of respiratory failure, cardiac insufficiency, fungal infection and intestinal obstruction in the two groups. The incidence of renal failure in group 1 was lower than that in group 2 (P = 0.0011), and the incidence of bacteremia was higher than that in group 2 (P = 0.000). Conclusion: Two sets of adult ALL chemotherapy regimens have better tolerance, higher CR rate and long-term survival rate; meanwhile, advanced age (31-60 years old) Ph-negative ALL patients may benefit from the scheme 2 with high drug content and low chemotherapy intensity. Background: Approximately 5-10% of patients with acute leukemia experienced invasive fungal infections in the course of chemotherapy, and in the case of infection, mortality in these patients tended to be up to 30-90%. Therefore, in order to reduce the incidence of invasive fungal infections in patients with acute leukemia, it is necessary to reduce the incidence of fungal infection related mortality, safety and effectiveness. Acute leukemia patients often have more organ dysfunction in chemotherapy, and therefore, the efficacy and safety of fungal infection prevention and treatment are equally important. Previous literature reports showed that Kapofen had better efficacy and safety in the treatment of invasive fungal infections[1-3], which was an ideal preventive drug for patient chemotherapy. In view of the cost and patient compliance factors, in the process of antifungal prophylaxis, after the initial treatment of Carpofen, the treatment was maintained with the Vinotecan tablet. In the prevention and treatment, in addition to the curative effect and safety problem, the effect of the treatment on the efficacy of the patients was not reported in the initial treatment. Objective: To analyze the effect of non-classified fungal infection in patients with acute leukemia on the response rate of patients with different risk stratification, and to evaluate the difference of survival rate of patients with different risk stratification. Methods: A retrospective analysis of 141 cases of acute leukemia with unclassified fungal infection from April 2010 to March 2013 was retrospectively analyzed. All patients received the net intravenous infusion of Capofen as the initial therapy, and orally treated with Vinotecan. According to the risk grouping of fungal infection, two groups were divided into two groups (the risk group and the high-risk group), and each group was divided into 2 groups (1 week group and 2 week group) according to the treatment course of Carpofen, and the difference of total reaction rate after treatment with different degree of risk stratification and different treatment courses was compared. The difference between the survival of patients under different risk groups was compared. The results showed that the overall response rate of patients after treatment was 75.9%, and the total reaction rates of the two groups were not significantly different (P = 0. 12 and P = 0. 19) at the first week and the fourth week of treatment. The total response rate of patients with high risk group was significantly higher than that in the first week (P = 0. 01 and P = 0.02) at the 2nd and 4th week evaluation. Conclusion: In the treatment of non-classified fungal infection of acute leukemia, it is necessary to select the appropriate treatment course of Kapofen according to the risk group of fungal infection. When the patients with high risk group choose Capofen as the initial treatment, the course of treatment should be up to 2 weeks. In the low-risk group, the treatment course for patients with low-risk group 1 week can meet the requirement.
【学位授予单位】：北京协和医学院
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R733.71
本文编号：2306961
[Abstract]:Background: Ph-negative acute lymphoblastic leukemia (ALL) is a kind of acute leukemia with high heterogeneity, there is no unified treatment plan internationally, the curative effect is uneven, and the effect of chemotherapy regimen on patients with different age groups also has certain difference. The improvement of the overall survival of traditional adult ALL chemotherapy has been very limited, but it has achieved good long-term curative effect. Therefore, more and more centers in the world have tried to treat adult Ph-negative ALL with children's ALL regimen and have achieved some results. Objective: To compare the difference between the efficacy and safety of traditional adult Ph-negative ALL treatment protocol and the new protocol for children's ALL, and to further analyze the difference between the two chemotherapy regimens on the efficacy of patients with different age groups. Methods: The data of 144 patients with Ph-negative ALL treated from Jan. 4, 2009 to Sep. 4, 2013 were retrospectively analyzed. According to the treatment plan, we divided into two groups: the traditional adult protocol (protocol 1) group and the new chemotherapy regimen for reference to childhood ALL (Scheme 2). The efficacy (complete remission rate, total survival, non-recurrence survival) and safety of the whole group were analyzed. Results: In 144 patients with Ph-negative ALL treated with chemotherapy, the overall response rate (CR) was 95.8%, the CR rate was 92.4%, the total survival (OS) rate was 59. 0% in 5 years, and the rate of non-recurrent survival (RFS) in 5 years was 48. 6%. There was no significant difference in CR rate (95. 6% and 96.1%, P = 0. 783), OS rate (65. 3% and 63. 4%, P = 0. 885) and 3-year RFS rate (56. 0% and 50. 0%, P = 0. 931) in group 1 and group 2. In group 1, the OS of patients aged 14 ~ 30 years was significantly better than those of 31 ~ 60 years old (63.6%: 54. 7%, P = 0. 7). The difference of RF5 was not statistically significant (3years RFS rate was 56. 5%: 57. 0%, P = 0. 472). In group 2, there was no significant difference in OS and RFS between 14 ~ 30 years old and 31 ~ 60 years of age (3-year OS rate was 65. 7%: 60. 3%, P = 0.423; 3 years RFS rate 51. 5%: 46. 6%, P = 0.0655). There was no significant difference in the incidence of respiratory failure, cardiac insufficiency, fungal infection and intestinal obstruction in the two groups. The incidence of renal failure in group 1 was lower than that in group 2 (P = 0.0011), and the incidence of bacteremia was higher than that in group 2 (P = 0.000). Conclusion: Two sets of adult ALL chemotherapy regimens have better tolerance, higher CR rate and long-term survival rate; meanwhile, advanced age (31-60 years old) Ph-negative ALL patients may benefit from the scheme 2 with high drug content and low chemotherapy intensity. Background: Approximately 5-10% of patients with acute leukemia experienced invasive fungal infections in the course of chemotherapy, and in the case of infection, mortality in these patients tended to be up to 30-90%. Therefore, in order to reduce the incidence of invasive fungal infections in patients with acute leukemia, it is necessary to reduce the incidence of fungal infection related mortality, safety and effectiveness. Acute leukemia patients often have more organ dysfunction in chemotherapy, and therefore, the efficacy and safety of fungal infection prevention and treatment are equally important. Previous literature reports showed that Kapofen had better efficacy and safety in the treatment of invasive fungal infections[1-3], which was an ideal preventive drug for patient chemotherapy. In view of the cost and patient compliance factors, in the process of antifungal prophylaxis, after the initial treatment of Carpofen, the treatment was maintained with the Vinotecan tablet. In the prevention and treatment, in addition to the curative effect and safety problem, the effect of the treatment on the efficacy of the patients was not reported in the initial treatment. Objective: To analyze the effect of non-classified fungal infection in patients with acute leukemia on the response rate of patients with different risk stratification, and to evaluate the difference of survival rate of patients with different risk stratification. Methods: A retrospective analysis of 141 cases of acute leukemia with unclassified fungal infection from April 2010 to March 2013 was retrospectively analyzed. All patients received the net intravenous infusion of Capofen as the initial therapy, and orally treated with Vinotecan. According to the risk grouping of fungal infection, two groups were divided into two groups (the risk group and the high-risk group), and each group was divided into 2 groups (1 week group and 2 week group) according to the treatment course of Carpofen, and the difference of total reaction rate after treatment with different degree of risk stratification and different treatment courses was compared. The difference between the survival of patients under different risk groups was compared. The results showed that the overall response rate of patients after treatment was 75.9%, and the total reaction rates of the two groups were not significantly different (P = 0. 12 and P = 0. 19) at the first week and the fourth week of treatment. The total response rate of patients with high risk group was significantly higher than that in the first week (P = 0. 01 and P = 0.02) at the 2nd and 4th week evaluation. Conclusion: In the treatment of non-classified fungal infection of acute leukemia, it is necessary to select the appropriate treatment course of Kapofen according to the risk group of fungal infection. When the patients with high risk group choose Capofen as the initial treatment, the course of treatment should be up to 2 weeks. In the low-risk group, the treatment course for patients with low-risk group 1 week can meet the requirement.
【学位授予单位】：北京协和医学院
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R733.71
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