【摘要】：目的觀察第二代酪氨酸激酶抑制劑達(dá)沙替尼對(duì)16例慢性粒細(xì)胞白血病(CML)進(jìn)展期患者的療效,為判斷疾病預(yù)后及調(diào)整治療方案提供一定的依據(jù)。對(duì)象和方法選擇2012年2月-2013年11月在安徽醫(yī)科大學(xué)第一附屬醫(yī)院及安慶市立醫(yī)院血液內(nèi)科確診的門診或住院的CML進(jìn)展期患者共16例,加速期3例,急變期13例,其中急淋變4例,急粒變5例,急單變4例。16例患者均口服達(dá)沙替尼治療原發(fā)病,其中3例給予70mg每日2次口服,4例給予140mg每日1次,8例100mg每日1次(其中1例在服用四個(gè)月后仍未緩解,后調(diào)整為150mg每日1次),1例給予50mg每日2次,8個(gè)月后調(diào)整為140mg每日1次口服。觀察患者服藥后的臨床療效,評(píng)估患者血液學(xué)反應(yīng)、遺傳學(xué)反應(yīng)以及不良反應(yīng)情況,直到隨訪結(jié)束或疾病進(jìn)展至死亡,計(jì)算生存時(shí)間。結(jié)果16例CML進(jìn)展期患者中有9例(56.25%)獲得CHR,其中達(dá)到緩解的中位時(shí)間為3個(gè)月,其中3例加速期患者有2例獲得CHR,13例急變期患者有7例獲得CHR;4例急淋變患者均獲得CHR,1例在緩解兩年后復(fù)發(fā),1例在緩解18個(gè)月后進(jìn)展為急髓變,2月后出現(xiàn)死亡,1例死于臍血移植;5例急粒變患者有3例獲得CHR,4例急單變患者均未獲得CHR。急變期患者的CHR及完全細(xì)胞遺傳學(xué)緩解(CcyR)率較加速期無統(tǒng)計(jì)學(xué)差異(P=1.000),急變期患者疾病進(jìn)展的發(fā)生率較加速期患者明顯增加,但差異無統(tǒng)計(jì)學(xué)意義(P=0.136)。急變期患者3及3級(jí)以上血液學(xué)不良反應(yīng)的發(fā)生率較加速期患者有所升高(P=0.518)。16例患者中有10例(62.5%)出現(xiàn)III-IV級(jí)血液學(xué)不良反應(yīng),短暫停藥或者促造血治療后血象有一定的恢復(fù)。非血液學(xué)不良反應(yīng)中,16例患者有3例(18.75%)出現(xiàn)胸腔積液,其中2例并發(fā)心包積液;有6例(37.5%)患者在服藥過程中出現(xiàn)發(fā)熱,其中1例反復(fù)并發(fā)肺部感染;有4例(25.0%)患者出現(xiàn)胃腸道反應(yīng),所有患者在服藥過程中均無肝功能損害及QTc間期延長(zhǎng)。16例患者中有10例死亡,其余患者的隨訪時(shí)間為2~24個(gè)月�；颊�2年生存率是37.5%(6例/16例),中位生存時(shí)間是12個(gè)月(95%CI:0-24.9個(gè)月)。結(jié)論達(dá)沙替尼治療CML進(jìn)展期患者療效較好,有較高的血液學(xué)及細(xì)胞遺傳學(xué)緩解率,對(duì)于加速期、急淋變及急粒變的CML患者可作為優(yōu)先的一個(gè)選擇,但對(duì)于急單變的患者,單用達(dá)沙替尼療效較差。由于疾病的異質(zhì)性,疾病緩解的時(shí)間長(zhǎng)短不一,待疾病恢復(fù)至慢性期時(shí),可考慮盡早行異基因造血干細(xì)胞移植(Allo-HSCT),以期望獲得更高的無進(jìn)展生存期(PFS)。達(dá)沙替尼可以為那些有條件行Allo-HSCT的部分患者爭(zhēng)取到時(shí)間和機(jī)會(huì)。
[Abstract]:Objective to observe the efficacy of dasatinib, a second generation tyrosine kinase inhibitor, in the treatment of 16 patients with chronic myeloid leukemia with advanced (CML), and to provide some basis for judging the prognosis of the disease and adjusting the treatment plan. Participants and methods A total of 16 patients with advanced CML diagnosed in the first affiliated Hospital of Anhui Medical University and Anqing Municipal Hospital from February 2012 to November 2013 were enrolled in this study. There were 3 patients in accelerated phase and 13 patients in acute stage, including 4 patients with acute lymphoid change, 5 patients with acute granulation and 4 patients with acute single change. All 16 patients were treated with dasatinib oral administration, of which 3 patients were given 70mg twice a day and 4 patients were given 140mg once a day. 8 cases of 100mg were treated once a day (1 case was not relieved after four months of administration, and then adjusted to 150mg once a day). One case was given 50mg twice a day and 8 months later adjusted to 140mg once a day. The clinical efficacy of the patients was observed, and the hematological reactions, genetic reactions and adverse reactions were evaluated until the end of follow-up or the progress of the disease to death, and the survival time was calculated. Results CHR, was obtained in 9 of 16 patients with advanced CML (56.25%). The median time to achieve remission was 3 months. Among them, 2 of 3 patients with accelerated CHR,13 and 7 of 7 patients with acute lymphoid disease had CHR,1 recurrence after two years of remission, 1 patient developed acute myelopathy after 18 months of remission, 1 died after 2 months of cord blood transplantation, and 1 patient died of cord blood transplantation after 2 months of remission, and 2 months after remission, 2 months later, 2 months after remission, 1 patient died of cord blood transplantation, 1 patient died of cord blood transplantation. CHR,4 was obtained in 3 of 5 patients with acute granulosis. CHR. was not obtained in 3 of 5 patients with acute granulosis. There was no significant difference in CHR and complete cytogenetic remission (CcyR) rate between patients with acute change and accelerated phase (P 鈮，

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