酪氨酸激酶抑制剂时代慢性粒细胞白血病的治疗

慢性粒细胞白血病(CML)的药物治疗经历了马利兰、羟基脲、干扰素及酪氨酸激酶抑制剂几个时代。马利兰和羟基脲仅能使患者获得血液学缓解,提高生存质量,并不改变其自然病程。干扰素可使部分患者获得细胞遗传学缓解,从而延长存活期,但遗憾的是仅少数患者受益。由于异基因造血干细     

中国慢性髓性白血病的治疗方案选择

自20世纪50年代"白消安"问世、1960年羟基脲成为一线治疗药物以来,羟基脲、白消安或联合化疗用于慢性髓性白血病(CML)的治疗,CML患者慢性期(CML-CP)平均为3～5年,这些药物仅仅能够减轻症状,并不能推迟加速期和急变期从而延长存活期.     

慢性髓性白血病临床诊疗指南与中国实践

伊马替尼作为第一代酪氨酸激酶抑制剂,给Ph+慢性髓性白血病(CML)患者带来了革命性的疗效,NCCN及ELN将其推荐为CML的首选治疗。但伊马替尼存在治疗费用高且不能停药、产生耐药、更长期的疗效尚待观察等限制。依据我国的国情,中国CML实践推荐针对不同患者,给予TKI、HSCT、干扰素及细胞毒药物结合的个体化治疗。     

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慢性粒细胞白血病(chronic myelogenous leukemia,CML)是恶性克隆性造血干细胞疾病,起病缓慢,其自然病程包括慢性期、加速期和急变期3个阶段。使用羟基脲等传统治疗方法,其慢性期病程在5年左右,加速期病程6~9个月,急变期病程3~6个月。CML的特征是具有BCR-ABL融合蛋白,ABL是一种酪氨酸激酶,与BCR形成融合蛋白后ABL的酪氨酸激酶组成性激活,导致CML的发生。伊马替尼(imatinib),以前称为STI571,是一种酪氨酸激酶抑制剂。其特异性的抑制BCR-ABL、PDGF受体和c-kit的活性。2001年5月,美国食品药品监督管理局(FDA)批准伊马替尼用于…     

Ph染色体阳性白血病患者经伊马替尼治疗后行异基因造血干细胞移植的疗效观察

目的探讨Ph染色体阳性白血病患者经伊马替尼治疗后行异基因造血干细胞移植的疗效。方法回顾性分析2001年6月至2005年6月北京大学人民医院血液病研究所住院的难治性Ph染色体阳性的39例白血病患者经伊马替尼治疗后再行异基因造血干细胞移植的效果,观察伊马替尼对造血重建、移植物抗宿主病(GVHD)、总存活率(OS)、无病存活率(DFS)、复发率和移植相关并发症的影响。结果伊马替尼治疗后,18例患者血液学完全缓解,9例骨髓缓解,4例部分缓解,4例无效或疾病进展,总有效率79.49%,无重度非血液学毒性反应;移植后中性粒细胞和血小板植活中位时间分别为14d和13.5d;Ⅱ~Ⅳ度和Ⅲ~Ⅳ度急性GVHD累积发生率分别为61.53%和15.38%;根据对伊马替尼治疗的效应分为完全缓解组和未完全缓解组,其3年预期OS和DFS分别为(73.51±9.61)%对(36.36±14.50)%和(61.28±12.37)%对(31.25±13.98)%,3年累积复发率为20.41%对75.00%;4例患者死于重度移植相关并发症。结论应用伊马替尼后行异基因造血干细胞移植是一种安全、有效的治疗难治性Ph染色体阳性白血病的方法,尤其达完全缓解后行移植,可望提高此类患者的临床治愈率。     

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慢性粒细胞白血病(CML)是具有特征性细胞遗传学改变(Ph染色体)和分子生物学特征(BCR-ABL表达)的干细胞克隆性疾病,临床主要表现为白细胞升高、外周血细胞核左移和脾肿大,分慢性期、加速期和急变期3个病期.1 造血干细胞移植治疗CML的机制     

伊马替尼血浆谷质量浓度与慢性粒细胞白血病慢性期疗效相关性研究

目的评价伊马替尼血浆谷质量浓度对慢性粒细胞白血病(CML)慢性期(CP)患者疗效的影响。方法收集2009年6月至2010年2月北京大学人民医院55例经标准剂量伊马替尼治疗的CML-CP患者,于治疗后3、6或12个月后检测伊马替尼血浆谷质量浓度。对疗效欠佳或治疗失败患者予增加伊马替尼剂量后3～6个月再次检测伊马替尼血浆谷质量浓度。结果服用400 mg/d伊马替尼患者中,血浆伊马替尼谷质量浓度为981～4170μg/L,平均为(1685±637)μg/L。治疗后18个月获得主要分子学反应(MMR)患者平均伊马替尼谷质量浓度(1881±669)μg/L显著高于未获得MMR患者(1262±346)μg/L(P<0.05)。17例未获MMR患者中,7例伊马替尼加量至600 mg/d后,其谷质量浓度显著升高,中位9个月时,6例(86%)获得MMR,而10例未加量者继续治疗,3例(30%)获得MMR(P=0.05)。结论伊马替尼的血浆谷质量浓度与CML-CP患者良好的分子学疗效相关。疗效不佳患者增加伊马替尼的剂量,有助于提高伊马替尼谷质量浓度和分子学疗效。     

尼洛替尼治疗伊马替尼耐药的慢性髓系白血病的临床观察

目的:探讨尼洛替尼在伊马替尼耐药的慢性髓系白血病( CML)患者中的疗效及不良反应.方法:9例伊马替尼耐药的CML患者,其中慢性期6例,进展期3例,持续口服尼洛替尼400 mg 2次/d,观察其疗效及不良反应.结果:6例CML慢性期患者,5例获得完全血液学反应,2例获得主要细胞遗传学反应；3例CML进展期患者均获得血液...     

伊马替尼治疗慢性粒细胞白血病患者的临床疗效及疗效影响因素分析

目的 探讨伊马替尼(IM)治疗慢性粒细胞白血病(CML)患者的临床疗效及疗效影响因素.方法 选择104例CML患者,临床分期为慢性期84例、加速期8例、急变期12例.慢性期IM用量为400 mg/d,加速期及急变期为600 mg/d,中位IM治疗时间为29(3 ～88)个月.治疗期间,每月复查血常规;每3～6个月复查骨髓细胞形态学、染色体核型和bcr-abl融合基因.比较各临床分期患者的临床疗效、药物安全性、临床耐药、治疗依从性等.结果 与加速期和急变期患者比较,慢性期患者治疗3个月时的完全血液学缓解率(CHR),12个月时的微小细胞遗传学缓解率(MCyR)、部分细胞遗传学缓解率(PCyR)、完全细胞遗传学缓解率(CCyR),治疗结束时的累积获得CHR、PCyR、CCyR、完全分子学反应率,以及1、3、5年总生存率、疾病无进展生存率均有统计学差异(P均＜0.05或＜0.01).应用IM治疗前时间≥90d、是否应用干扰素治疗、依从性不佳是影响IM疗效的不利因素(P均＜0.05).EUTOS评分低危患者获得MCyR、PCyR和CCyR的比例显著高于高危患者(P均＜0.05).慢性期患者的原发耐药率为9.5％,继发耐药率为14.3％;加速期、急变期患者原发耐药率分别为37.5％、66.7％,继发耐药率分别为25.0％、16.7％.结论 IM治疗CML慢性期患者的血液学、细胞遗传学、分子生物学缓解率高,不良反应小,在疾病早期应用可提高疗效;加速期及急变期患者IM耐药率较高,EUTOS评分高、依从性不佳可影响IM疗效.     

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慢性髓性白血病(chronic myelogenous leukemia,CML)是以粒系增生为主,伴有特征性遗传学标志Ph染色体的骨髓增殖性疾病(MPD)。Ph染色体是9号和22号染色体断裂后交互易位的结果,导致ABL与BCR基因序列融合,进而产生一段210ku具有酪氨酸激酶活性的融合蛋白(P210BCR-ABL),该蛋白使信号传导途径异常激活,下游信号持续磷酸化,MYC和BCL-2转录增加,导致造血干细胞增殖失控,凋亡受阻,粘附功能缺陷,细胞发生恶性转化。推测恶变发生在骨髓多能干细胞阶段。CML年发病率(1~1.5)/10万。各年龄均可发病,中位年龄50~60岁。病程分为相对缓和的慢…     

Marrow transplantation for the treatment of chronic myelogenous leukemia

One hundred ninety-eight patients with chronic myelogenous leukemia received marrow transplants after intensive chemotherapy and total body irradiation. Multivariate analysis showed disease status at time of transplantation to be the most powerful predictor of survival. The probability of long-term survival for allogeneic graft recipients was 49% for 67 patients in the first chronic phase, 58% for 12 in the second chronic phase, 15% for 46 in the accelerated phase, and 14% for 42 in the blastic phase. The major cause of death was interstitial pneumonia for patients in the chronic phase, and relapse for those in the blastic or accelerated phases. Factors favoring survival were early transplantation, age less than 30 years, and absence of severe graft-versus-host disease. Splenectomy or spleen size did not influence survival. For recipients of syngeneic grafts survival probability was 87% for 16 patients in the chronic phase, 27% for 7 in the accelerated phase, and 12% for 8 in the blastic phase. Of the 198 patients, 71 are alive without Philadelphia chromosomes 1 to 9 years after receiving their graft. All but 4 long-term disease-free survivors have Karnofsky performance scores of 80% or better.     

血液系统疾病靶向治疗的现状与进展伊马替尼治疗慢性粒细胞白血病的最新进展

慢性粒细胞白血病(CML)是一种以携带费城染色体(Ph)异常造血细胞克隆扩增为特征的骨髓增殖性血液疾病.t(9;22)q(34;11)染色体易位导致BCR-ABL融合基因的形成,该融合基因编码产生具有高酪氨酸激酶活性的BCR-ABL融合蛋白,成为CML发病的主要原因.     

High-dose cytarabine for the treatment of blastic phase chronic myelogenous leukemia

High-dose cytarabine chemotherapy regimens were given to 22 patients for the treatment of blastic phase chronic myelogenous leukemia. Bone marrow aplasia occurred in 21 of these patients; in one patient the marrow was not cleared of blasts. In five patients (26%), blastic phase promptly recurred. Eight patients (37%) died of infection or hemorrhage during the period of marrow aplasia before bone marrow recovery. Seven patients achieved complete remission and one achieved partial remission, but the duration of the remission was brief [median, 98 days (range, 52-345)]. One patient received consolidation therapy with an additional course of high-dose cytarabine and maintained remission for 345 days. These results suggest that alternative approaches to the treatment need to be explored.     

Emergence of chronic myelogenous leukemia during treatment for essential thrombocythemia

A 72-year-old male patient was initially diagnosed with essential thrombocythemia (ET), a Philadelphia chromosome-negative (Ph1⁻) chronic myeloproliferative disorder (CMPD), and was treated with hydroxyurea (HU). After 9 years of diagnosis of ET, his peripheral leukocytes gradually increased, while his platelet count showed a decrease. Bone marrow analysis disclosed Ph-positive chronic myelogenous leukemia (CML) in the chronic phase. Administration of imatinib mesylate (IM), a Bcr–Abl tyrosine kinase inhibitor (TKI), induced complete hematologic response in a month, but was discontinued after 4 months because of Grade 3 pleural effusion (PE). The treatment was switched to nilotinib which successfully induced a complete cytogenetic response (CCyR) after 5 months of TKI therapy and resolved the PE. Despite CCyR, however, ET recurred. Since then, the patient has been treated for 8 months with a combination of nilotinib and HU which has successfully controlled both CML and ET. This report includes a review of the characteristics of 15 reported cases with co-occurrence of CML and Bcr–Abl-negative CMPDs, including ours. Although rare, care needs to be taken since, despite the often similar clinical features of the two diseases, they require completely different treatments.