【摘要】：研究背景:Ph陰性急性淋巴細(xì)胞白血病(ALL)是一種異質(zhì)性較高的急性白血病,國(guó)際上尚無(wú)統(tǒng)一的治療方案,療效參差不齊;同時(shí)化療方案對(duì)不同年齡段患者的療效也存在一定的差異。傳統(tǒng)成人ALL化療方案對(duì)整體生存的改善已十分有限,反觀(guān)兒童ALL,卻取得了較好的遠(yuǎn)期療效。因此國(guó)際上越來(lái)越多的中心嘗試應(yīng)用兒童ALL方案治療成人Ph陰性ALL,并取得了一定的成效。研究目的:比較傳統(tǒng)成人Ph陰性ALL治療方案和借鑒兒童ALL的新方案在療效及安全性上的差異,并進(jìn)一步分析這兩種化療方案對(duì)不同年齡段患者療效的差異。研究方法:回顧性分析2009年1月4日至2013年9月4日收治的144例初治Ph陰性ALL患者資料,根據(jù)治療方案分為傳統(tǒng)的成人方案(方案1)組和借鑒兒童ALL的新化療方案(方案2)組,分析其整體及不同分組條件下的療效(完全緩解率、總生存、無(wú)復(fù)發(fā)生存)及安全性。研究結(jié)果:144例初治成人Ph陰性ALL患者接受化療后,總完全緩解(CR)率為95.8%,1個(gè)療程CR率為92.4%,5年總生存(OS)率為59.0%,5年無(wú)復(fù)發(fā)生存(RFS)率為48.6%。其中方案1組和方案2組在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)差異均無(wú)統(tǒng)計(jì)學(xué)意義。方案1組中,14～30歲患者的OS要明顯優(yōu)于31～60歲患者(3年OS率69.6%:54.7%,P=0.042),RF5差異則無(wú)統(tǒng)計(jì)學(xué)意義(3年RFS率56.5%:57.0%,P=0.472)。方案2組中,14～30歲患者與31～60歲患者在OS及RFS上差異均無(wú)統(tǒng)計(jì)學(xué)意義(3 年 OS 率 65.7%:60.3%,P=0.423;3 年 RFS 率 51.5%:46.6%,P=0.655)。兩組化療方案在呼吸衰竭、心功能不全、真菌感染及腸梗阻發(fā)生率上差異均無(wú)統(tǒng)計(jì)學(xué)意義,方案1組的腎功能不全發(fā)生率要低于方案2組(P=0.011),菌血癥發(fā)生率高于方案2組(P=0.000)。結(jié)論:兩套成人ALL化療方案耐受性較好,具有較高的CR率及長(zhǎng)期生存率;同時(shí),高齡(31～60歲)Ph陰性ALL患者有可能從非骨髓抑制藥物含量高、化療強(qiáng)度低的方案2中受益。研究背景:急性白血病患者中在化療過(guò)程中約有5-10%的患者會(huì)發(fā)生侵襲性真菌感染,一旦發(fā)生感染,這部分患者的死亡率往往高達(dá)30-90%。因此,為了降低急性白血病患者在化療過(guò)程中侵襲性真菌感染的發(fā)生率、降低真菌感染相關(guān)死亡率,安全有效的預(yù)防措施是否必要。急性白血病患者在化療中往往合并有較多的臟器功能異常,因此,真菌感染預(yù)防治療的療效及安全性同樣重要。既往文獻(xiàn)報(bào)道顯示,卡泊芬凈在治療侵襲性真菌感染時(shí)具有較好的療效及安全性[1-3],是患者化療期間較為理想的預(yù)防藥物。考慮到費(fèi)用及患者依從因素,抗真菌預(yù)防過(guò)程中,卡泊芬凈初始治療后經(jīng)常序貫以伏立康唑片維持治療。預(yù)防治療中,除了療效及安全性問(wèn)題外,初始治療中,卡泊芬凈療程的長(zhǎng)短對(duì)患者療效的影響尚無(wú)相關(guān)報(bào)道。研究目的:分析急性白血病患者中未分類(lèi)真菌感染在不同危險(xiǎn)度分層下,卡泊芬凈療程的長(zhǎng)短對(duì)患者反應(yīng)率的影響,并評(píng)價(jià)不同危險(xiǎn)度分層下,患者生存率的差異。研究方法:回顧性分析2010年4月-2013年3月收治的141例伴有未分類(lèi)真菌感染的急性白血病患者病例資料,所有患者均接受卡泊芬凈靜脈輸注為初始治療,并以伏立康唑口服為序貫治療。按照真菌感染的危險(xiǎn)度分組分為2組(標(biāo)危組和高危組),每一組按照卡泊芬凈療程再分為2組(1周組和2周組),對(duì)比不同危險(xiǎn)度分層下,不同療程的卡泊芬凈治療后總反應(yīng)率的差異;對(duì)比不同危險(xiǎn)度分組下患者生存的差異。研究結(jié)果:患者治療后整體反應(yīng)率達(dá)75.9%,標(biāo)危組患者在治療第2周和第4周評(píng)價(jià)療效時(shí),1周卡泊芬凈組和2周卡泊芬凈組總反應(yīng)率無(wú)明顯差異(P=0.12和P=0.19);高危組患者在治療第2周和第4周評(píng)價(jià)療效時(shí),2周卡泊芬凈組的總反應(yīng)率均明顯高于1周卡泊芬凈組(P=0.01和P=0.02)。結(jié)論:治療急性白血病未分類(lèi)真菌感染時(shí),需按照真菌感染的危險(xiǎn)度分組選擇合適的卡泊芬凈療程,高危組患者選擇卡泊芬凈作為初始治療時(shí),療程應(yīng)達(dá)2周,而低危組患者療程1周的卡泊芬凈即可達(dá)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.
【學(xué)位授予單位】：北京協(xié)和醫(yī)學(xué)院
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2016
【分類(lèi)號(hào)】：R733.71

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