一代和二代酪氨酸激酶抑制剂治疗 对CML染色体的影响及疗效

目的 探讨一代和二代酪氨酸激酶抑制剂治疗对慢性粒细胞白血病(CML)患者染色体的影响及疗效。方法 用常规细胞遗传学法对80例Ph+的CML患者进行遗传学分析,同时对比一代和二代酪氨酸激酶抑制剂治疗后CML患者染色体的改变情况及疗效。结果 80例Ph+的CML患者中有11例合并其他的染色体数目及结构异常,其中有10例对伊马替尼耐药或不耐受。伊马替尼(TKI-Ⅰ)治疗的40例患者中有35例达到持续完全细胞遗传学缓解(complete cytogenetic remission,CCyR)(占87.5%),其中有7例3个月时获得CCyR(占17.5%),10例6个月时获得CCyR(占25%),13例12个月时获得CCyR(占32.5%),5例18个月时获得CCyR(占12.5%); 达沙替尼/尼罗替尼(TKI-Ⅱ)治疗的40例患者中有33例达到持续完全细胞遗传学缓解(CCyR)(占82.5%),其中有16例3个月时获得CCyR(占40%),9例6个月时获得CCyR(占22.5%),5例12个月时获得CCyR(占12.5%),3例18个月时获得CCyR(占7.5%)。结论 合并其他染色体异常的Ph+CML患者更容易对伊马替尼产生耐药或不耐受性,尤其是加速期和急变期,一代和二代酪氨酸激酶抑制剂对CML的治疗在长期疗效上相差不大,但近期效果二代优于一代。     

404例慢性粒细胞白血病的染色体核型研究

目的探讨慢性粒细胞白血病(CML)不同时期骨髓细胞染色体核型的变化特点及临床意义。方法采用短期培养法制备骨髓细胞染色体标本,应用R显带技术对该院404例CML患者的骨髓染色体核型进行回顾性分析。结果 404例患者中Ph染色体阳性376例(93.1%),Ph染色体阴性但bcr/abl阳性28例(6.9%)。376例Ph染色体阳性患者中,具有典型Ph易位者360例,具有变异易位者16例(复杂变异易位14例,简单变异易位2例)。16例变异易位患者慢性期10例,急变期6例。伴额外染色体异常者80例(19.8%),其中慢性期32例,占CML慢性期患者(304例)的10.5%,以-Y、+8为主;急变期48例,占急变期患者(100例)的48%,以i(17)、+8、+Ph最多见。CML急变期伴额外染色体异常的比例高于慢性期(P0.01)。结论 Ph染色体是CML的细胞遗传学标志,Ph染色体可表现为典型易位和变异易位,变异易位在慢性期和急变期都可出现。CML急变期伴额外染色体异常的比例高于慢性期,CML病程出现额外染色体异常预示病程进入加速或急变期。     

伊马替尼治疗Ph阳性慢性粒细胞白血病引起的骨髓形态学变化

目的　观察伊马替尼治疗Ph阳性慢性粒细胞白血病 (CML)引起的骨髓形态学变化 ,并探讨其与血液学、遗传学疗效之间的关系。方法　 117例Ph阳性CML患者 ,包括干扰素治疗失败的慢性期 5 4例、加速期 4 1例、急髓变期 2 2例 ,日服伊马替尼 4 0 0或 6 0 0mg,持续 18个月以上。结果　治疗18个月内 ,各期患者骨髓增生程度显著降低、原始粒细胞 早幼粒细胞显著减少、骨髓无CML特征的比例显著增加 ,慢性期和加速期患者粒、红细胞比例显著降低、巨核细胞数量显著减少 (P值均 <0 0 5 )。获得血液学疗效者骨髓形态持续正常。治疗中发生骨髓增生低下或极度低下还是增生活跃以上与血液学和遗传学疗效密切相关 :慢性期患者其遗传学有效率分别为 5 8.8%和 86 .5 % (P =0 .0 35 ) ,加速期患者血液学完全缓解率分别为 2 6 .3%和 75 .0 % (P =0 .0 0 4 ) ,急变期患者生存期短于 6个月者比例分别为 77.8%和 16 .7% (P =0 .0 0 9)。在CML进展期 ,治疗 1个月时骨髓形态学无CML特征与有CML特征者相比 ,加速期患者 18个月疾病进展率显著降低 (分别为 2 5 .0 %和 75 .0 % ,P =0 .0 2 8)、总生存率显著升高 (分别为 75 .0 %和 11.8% ,P =0 .0 0 4 ) ;急变期患者获得血液学效应的比例显著增加 (分别为 10 0 .0 %和 4 0 .0 % ,P =0     

尼罗替尼治疗对伊马替尼耐药或不耐受的慢性粒细胞白血病临床分析

目的 评价对伊马替尼耐药或不耐受的慢性粒细胞白血病(CML)患者接受尼罗替尼治疗的安全性和疗效.方法 35例对伊马替尼耐药或不耐受CML患者接受尼罗替尼治疗,400 mg,口服,每日2次,评估其疗效、不良反应、总体生存和疾病进展情况.结果 35例对伊马替尼耐药或小耐受的CML患者,中位尼罗替尼治疗时间11个月,中位随访时间19个月.尼罗替尼治疗相关的非血液学小良反应多为1～2级,主要为胆红素升高(76%)和皮疹(46%).3～4级血液学不良反应包括血小板减少(37%)、中性粒细胞减少和贫血(均为26%).患者大多可耐受.进展期(包括加速期和急变期)患者的3～4级血液学不良反廊发牛率明显高于慢性期.35例接受尼罗替尼治疗的患者中,CML慢性期患者获得主要细胞遗传学缓解率为38.5%,明显高于进展期患者(22.2%).达主要细胞遗传学缓解的中位时间为3个月.进展期患者发生疾病进展的比例明显高于慢性期.18个月预期总体生存率为(93.5±1.0)%.结论尼罗替尼为对伊马替尼耐药和不耐受的CML患者提供了一个有效并安全的治疗于段.尼罗替尼治疗慢性期CML更为安全和有效.     

伊马替尼治疗慢性粒细胞白血病有效性和安全性观察

目的观察甲磺酸伊马替尼治疗慢性粒细胞白血病（CML）的有效性与安全性。方法 51例CML病人给予伊马替尼治疗,观察其血液学、细胞遗传学、分子学反应以及不良反应、总生存和疾病进展情况。结果CML慢性期病人治疗3个月时97.8%（45/46）获得完全血液学缓解;用药1年后,79.4%（27/34）获得完全细胞遗传学缓解,5.9%（2/34）获得部分细胞遗传学缓解,2.9%（1/34）获得次要细胞遗传学缓解,5.9%（2/34）获得微小细胞遗传学缓解,5.9%（2/34）未获得遗传学反应,29.4%（10/34）获得完全分子遗传学缓解;1、2、3年总生存率分别为100.0%、97.0%、91.6%,疾病无进展生存率分别为100.0%、85.3%、73.1%。3例CML加速期病人1例获得完全血液学缓解,1例获得完全细胞遗传学缓解,1例获得部分细胞遗传学缓解。2例CML急变期病人均死亡,总病程分别为9、15个月。结论伊马替尼治疗CML慢性期病人,完全血液学缓解率和细胞遗传学缓解率高,且不良反应少,但对加速期和急变期病人疗效欠佳。     

达沙替尼对中国慢性髓性白血病伊马替尼耐药或不耐受患者疗效及安全性研究

目的 确证达沙替尼在中国慢性髓性白血病(CML)伊马替尼耐药或不耐受的患者中的疗效及安全性.方法 119例对伊马替尼耐药或不耐受的CML患者接受达沙替尼治疗,其中慢性期59例、加速期25例、急变期35例.慢性期患者剂量为100 mg每日1次,加速期及急变期患者剂量为70 mg每日2次,评估患者血液学反应、遗传学反应、无进展生存(PFS)、总生存(OS)以及不良反应情况.结果 慢性期、加速期、急变期疗程中位数分别为19.32、20.99及3.22个月.59例慢性期患者的完全血液学缓解(CHR)率为91.5％,获得主要细胞遗传学缓解(MCyR) 30例(50.8％),其中25例(42.4％)为完全细胞遗传学缓解(CCyR),达到MCyR的中位时间为12.1周;获得MCyR的慢性期患者无一例出现进展及死亡.25例加速期患者的CHR率、主要血液学缓解(MaHR)率分别为52.0％、84.0％,达到CHR、MaHR的中位时间为16.0、12.1周,获得MCyR 10例,其中9例为CCyR;加速期患者中位PFS期为25.7个月.35例急变期患者的CHR率、MaHR率分别为17.1％、31.4％,达到CHR、MaHR的中位时间均为12.1周;MaHR的中位持续时间为11.2个月;8例急变期患者获得MCyR,MCyR的中位持续时间为13.2个月;急变期患者的中位PFS、OS期分别为4.3、16.7个月.达沙替尼治疗相关的3～4级血液学不良反应常见,但通过剂量调整以及支持治疗可得到有效控制.慢性期患者发生3～4级中性粒细胞(ANC)、血小板减少比例分别为52.5％、61.0％,进展期患者发生率均在80％以上,仅1例进展期患者因为达沙替尼引起的血小板减少而终止治疗.达沙替尼相关的非血液学不良反应主要包括1～2级胸腔积液、头痛、肺炎、腹泻,总体而言进展期患者不良反应发生率高于慢性期患者.结论 达沙替尼治疗对伊马替尼耐药或不耐受的各期CML患者可获得相对持久的血液学甚至细胞遗传学缓解且耐受性良好.     

伊马替尼治疗95例慢性粒细胞白血病的远期疗效及其影响因素分析

目的 分析伊马替尼治疗慢性粒细胞白血病(CML)的疗效和患者生存情况,并初步探讨影响伊马替尼疗效的因素.方法 对2002年5月至2006年5月接受伊马替尼治疗的95例CML患者随访至2006年10月31日,分析患者的治疗转归及相关影响因素.结果 ①慢性期组伊马替尼治疗后12个月95.5%患者获得完全血液学缓解(CHR);其中遗传学资料完整的52例患者中初治19例,复治33例,初治组治疗后6、12、18、24、30个月的主要细胞遗传学缓解(MCyR)率分别为84.2%、84.2%、89.5%、89.5%和94.7%,复治组分别为36.4%、39.4%、39.4%、39.4%和39.4%,两组比较差异有统计学意义(P＜0.01);全组患者治疗后12、24、36、50个月预期生存率分别为(98.1±1.9)%、(87.8±7.1)%、(81.9±8.7)%和(81.9±8.7)%.②加速期组伊马替尼治疗后12个月70%患者获得CHR,10%获得MCyR;治疗后12、24和36个月预期生存率分别为(63.0±17.7)%、(15.8±14.3)%和(15.8±14.3)%.③急变期组伊马替尼治疗后6个月57.9%患者获得CHR;治疗后12、24个月预期生存率分别为(40.6±12.3)%和0.④对慢性期组进行COX多因素预后分析显示,伊马替尼治疗前有无其他治疗是影响无进展生存和获得MCyR的独立预后不良因素.结论 ①伊马替尼作为一线治疗药物用于CML慢性期,对患者生存质量的改善明显优于作为替换治疗药物或用于加速、急变期治疗,因此伊马替尼应明确作为首选的一线治疗药物.②伊马替尼治疗加速期和急变期CML也能获得一定血液学、遗传学疗效,延长患者生存期.     

实时定量RT-PCR监测慢性粒细胞白血病患者伊马替尼治疗过程中bcr/abl mRNA水平

目的观察甲磺酸伊马替尼(简称伊马替尼)治疗Ph+慢性粒细胞白血病(CML)患者骨髓bcr/ablmRNA水平的变化。方法采用实时定量(Realtimequantitative)RTPCR(RQPCR)技术连续监测34例α干扰素治疗无效Ph+CML患者在伊马替尼治疗前后不同时间120份骨髓标本bcr/ablmRNA水平。治疗前骨髓Ph+细胞百分率均≥95%。结果RQPCR的敏感度为10pgRNA,标准品日间差及日内差均<5%。10例伊马替尼治疗前标本中位bcr/ablmRNA水平为5.79%,各例之间差异甚大(0.24%～60.90%)。72份Ph+细胞百分率为0%～94%的治疗后标本bcr/ablmRNA水平与Ph+细胞百分率显著相关(r=0.82,P<0.001)。7例治疗12个月内达到完全遗传学缓解(CCyR)的患者bcr/ablmRNA水平随治疗时间延长而迅速降低,可供分析的6例患者治疗3个月时较治疗前下降65.9%～98.8%。达到CCyR后,bcr/ablmRNA水平随治疗时间延长继续下降,直至为0。4例治疗12个月后获得显著遗传学缓解患者(Ph+细胞百分率均<35%)bcr/ablmRNA水平缓慢下降,可供分析的3例患者治疗3个月时的bcr/ablmRNA水平分别比治疗前下降2.5%、18.5%及61.6%。5例持续遗传学无效,并且维持在慢性期的患者bcr/ablmRNA水平1例缓慢下降,2例缓慢上升,2例基本不变。4例治疗中发生急变的患者bcr/ablmRNA水平均逐步升高。结论对于伊马替尼     

伊马替尼治疗慢性粒细胞白血病26例临床观察

我们应用伊马替尼(商品名格列卫)治疗37例Ph染色体阳性慢性粒细胞白血病(CML)患者,现将疗程在30d以上并随访资料完整的2 6例临床研究结果报告如下。对象和方法1　研究对象　2 6例白血病患者均符合FAB诊断标准,全部表现Ph染色体和bcr/abl融合基因阳性,其中CML慢性期(CP) 7例(诊断后病程平均3年) ,加速期(AP) 5例,急变期(BP) 1 4例,男性1 5例,女性1 1例,中位数年龄38(1 2～6 3)岁。CML BP的类型:急性非淋巴细胞白血病(ANLL) 1 3例,急性淋巴细胞白血病(ALL) 1例。急变前的中位病程1 9.5(7～1 1 2 )个月。应用伊马替尼治疗前曾隔日…     

干扰素-α治疗Ph+慢性粒细胞白血病的细胞遗传学反应分析

为了研究慢性粒细胞白血病 (CML)慢性期患者应用干扰素 α (IFN α)治疗后细胞遗传学疗效及其影响预后的因素 ,对我院 10年来 12 8例CML慢性期患者单用IFN α或联用化疗药物后细胞遗传学变化、核型演变及与临床有关特征的关系进行了回顾性分析。核型分析全部应用G 显带 ,部分联合应用荧光染色体原位杂交技术检测。结果表明 :①所有患者均获血液学缓解。② 118例Ph染色体标准易位患者中 36例 (30 .8% )获细胞遗传学反应 ,其中 2 0例 (17.1% )Ph染色体仍 >35 % ,13例 (11.1% )Ph染色体 <35 % ,3例 (2 5 % )Ph染色体为 0 ,达完全细胞遗传学缓解 ,细胞遗传学有效应者共 16例 (13.6 % )。③ 7例复杂变异易位患者中 4例获细胞遗传学反应 ,其中2例 (14 .3% )Ph染色体 >35 % ,2例 (14 .3% )Ph染色体 <35 % ,无 1例Ph染色体为 0 ;3例简单变异易位患者无 1例获细胞遗传学疗效。④IFN α治疗后影响细胞遗传学疗效的因素有 :性别、初诊病情、IFN α是否联用其他化疗药物及是否持续治疗。⑤IFN α治疗并不能防止CML疾病进展。结论 :①每周IFN α 6 0 0 - 90 0万U单用或联合Bu/Hu可使 11.1%的标准易位和少数复杂变异易位Ph+ CML患者获主要细胞遗传学效应 ,但不能防止疾病进展 ;②Ph变异易位并不预示IFN α疗效不佳 ;     

伊马替尼治疗慢性粒细胞白血病疗效分析

目的分析伊马替尼治疗慢性粒细胞白血病（CML）的疗效,进一步探讨影响伊马替尼疗效的因素。方法63例慢性粒细胞白血病患者,给予口服伊马替尼治疗;其中慢性期（CP）51例,加速期（AP）5例,急变期（BP）7例。结果完全血液学缓解率（CHR）：CP94．1％（48／51）,AP40．0％（2／5）,BP28．6％（2／7）,累计82．5％（52／63）;完全遗传学缓解率（CCR）：CP60．8％（31／5]）,AP20．0％（1／5）,BP14．3％（1／7）,累计52．4％（33／63）;部分遗传学缓解率（MCR）：CP82．4％（42／51）,AP40．0％（2／5）,BP28．6％（2／7）,累计73．0％（46／63）。可评估分子效应的21例患者中,8例达完全分子效应（38．1％）,4例发生主要分子效应（19．0％）,累计57．1％（12／21）。血液学不良反应主要为不同程度的血细胞减少和骨髓抑制,可通过调整剂量或药物治疗控制。非血液学不良反应（如恶心、水肿等）发生率较高,但大多程度轻微且可耐受或自行消失。结论伊马替尼治疗慢性粒细胞白血病有较高的完全血液学缓解率和遗传学缓解率及分子效应,不良反应轻微。常见血液学不良反应为中性粒细胞减少、血小板减少,非血液学不良反应为消化道反应及轻度水肿,大多程度轻微,患者能够耐受。个体化正规治疗有望进一步提高疗效。     

Dasatinib treatment for imatinib resistant or intolerant patients with chronic myeloid leukaemia

Chronic myeloid leukaemia (CML) is a genetically associated malignancy of haematopoietic stem cells, characterized by a t(9;22) translocation that forms the Philadelphia chromosome and creates a novel fusion gene, BCR-ABL. Treatment with molecular-targeted therapy is usually initiated with imatinib, an inhibitor of BCR-ABL tyrosine kinase. Imatinib resistance is, however, observed in some CML patients, especially in those with advanced disease. Through computerized literature searches, a systematic analysis was conducted to examine the efficacy and benefits of dasatinib therapy for imatinib resistant or intolerant CML patients in the chronic phase (CP), accelerated phase (AP) and fatal blast crisis phase (BC). In terms of major haematological and cytogenetic responses, this meta-analysis showed no significant differences in dasatinib treatment between myeloid BC-CML and lymphoid BC-CML patients with imatinib resistance or intolerance. Dasatinib therapy was, however, significantly more effective in improving major haematological and cytogenetic responses for CP-CML patients than for AP-CML patients with imatinib resistance or intolerance.     

Imatinib mesylate in conjunction with allogeneic hematopoietic stem cell transplantation in patients with Philadelphia chromosome positive leukemias: report of 4 cases

We described here four patients diagnosed with Philadelphia chromosome positive (Ph+) leukemia, consisting of chronic myeloid leukemia (CML) (n=2) and Ph+ acute lymphoblastic leukemia (ALL) (n=2). All patients were treated with imatinib mesylate (300-400 mg/day) for the treatment of relapsed CML after allogeneic hematopoietic stem cell transplantation (SCT) (n=2), relapsed Ph+ ALL after SCT (n=1), and Ph+ ALL preceding SCT (n=1). Significant clinical and molecular responses were observed in all patients and three of them achieved sustained molecular remission. Imatinib was well tolerated and did not induce noticeable graft versus host disease although one patient presented severe skin rash (Grade III). Notably, serum cyclosporine A concentration increased after the initiation of imatinib treatment, probably through competitive inhibition of P450 3A4 isoenzyme. Our data suggest that imatinib in conjunction with SCT for the Ph+ leukemia may be a promising treatment strategy.     

慢性髓系白血病急变期分子遗传学研究进展

9号和22号染色体相互易位产生Ph染色体及BCR-ABL融合基因,几乎在所有慢性髓系白血病（CML）出现,BCR-ABL编码的蛋白具有持续增高的酪氨酸激酶活性,使白血病细胞异常增殖。急变期是CML的晚期,在此期间常常出现其它附加染色体和分子的改变。大量研究表明,BCR-ABL基因与其他失调的基因共同作用并异常激活下游的信号传导通路,促进了疾病的进展。酪氨酸激酶抑制剂伊马替尼对大多数慢性期CML患者治疗效果显著。IRIS5年的临床试验显示：用伊马替尼治疗的98%患者达血液学完全缓解,92%患者达主要细胞遗传学缓解,87%患者达完全细胞遗传学缓解。然而,仍有少数慢性期和大多数进展期患者用伊马替尼治疗疗效欠佳。在耐药机制的研究中发现ABL激酶区点突变与临床耐药关系密切。第二代酪氨酸激酶抑制剂可改善伊马替尼耐药,本文就急性变的分子机制、伊马替尼耐药等做一综述。     

1193例慢性粒细胞白血病细胞及分子遗传学分析

目的了解国内慢性粒细胞白血病（CML）不同病期染色体核型及其演变和ber—abl融合基因特点。方法对1193例CML患者的染色体核型及524例CML患者的ber-abl融合基因资料进行回顾性分析。染色体的检测采用R显带技术，融合基因检测采用RT-PCR技术。结果在所有病例中，Ph染色体阳性（Ph^＋）患者占98．07％，Ph^-患者占1．93％。在Ph^＋患者中，95．64％为典型Ph染色体阳性，4．36％为变异型Ph染色体阳性。11．88％的典型Ph^＋患者发生染色体核型演变。急变期、加速期和慢性期染色体核型演变的发生率分别为49．04％、27．78％及7．94％。在所有典型Ph^＋患者中，发生染色体核型演变后最常见的附加染色体异常类型为＋Ph（14．62％），＋8（10．77％）和-21（7．69％）。急变期和加速期最常见的附加染色体异常类型为＋Ph（28．57％），＋8（16．67％）和＋19（7．14％）；慢性期最常见的附加染色体异常为-21（10．26％），＋Ph（8．97％）和＋8（8．97％）。附加染色体异常联合出现类型以＋Ph与＋8的联合最多（3．60％）。在所有524例检测过融合基因的标本中，h3a2（＋）为54．01％，b2a2（＋）为27．67％。结论国内CML患者染色体的核型及演变可能有着自己的特点。     

Efficacy and safety of imatinib in treatment of 151 chronic myeloid leukemia patients]

OBJECTIVE: To evaluate the safety and efficacy of imatinib in treatment of chronic myeloid leukemia (CML) patients. METHODS: From December 2003 to March 2007, 151 patients entered Glivec International Patient Assistance Program (GIPAP) in our center and received imatinib therapy. The overall and progression free survival, hematologic, cytogenetic and molecular response, and adverse events were evaluated. The factors associated with outcome of imatinib therapy were also analysed. RESULTS: One hundred and forty-two patients were evaluable with a median follow-up duration of 21.5 (6 -78) months. (1) The rate of cumulative complete hematologic response (CHR), major cytogenetic response (MCyR), complete cytogenetic response (CCyR) and complete molecular response (CMoR) in chronic phase (CP) CML patients were 96.9%, 82.6%, 76.1% and 29.4%, respectively. These rates were significantly higher in patients with CP than in those with accelerated phase (AP) and blast crisis (BC) (P < 0.0001). (2) The overall survival (OS) rates at 1, 2 and 3 year were 100%, (97.3 +/- 1.9)% and (95.8 +/- 2.4)% for CP patients, they were (84.7 +/- 8.2)%, (77.0 +/- 10.4)% and (69.3 +/- 11.9)% for AP patients, and (62.9 +/- 8.9)%, (41.9 +/- 9.2)% and (28.5 +/- 9.1)% for BC patients, respectively (P < 0.0001). The progression-free survival (PFS) rates at 1, 2 and 3 year were (98.9 +/- 1.1)%, (93.9 +/- 2.7)%, (93.9 +/- 2.7)% for CP patients, (68.9 +/- 10.6)%, (61.3 +/- 11.9)%, (61.3 +/- 11.9)% for AP patients, (36.4 +/- 8.8)%, (25.4 +/- 8.1)%, (10.1 +/- 8.2)% (P < 0.0001) for BC patients respectively. (3) Among 92 CP patients, the rates of MCyR and CCyR in newly diagnosed patients were significantly higher than those in interferon therapy failure patients (P = 0.015, P = 0.010). Patients obtained CCyR at 12 months after the initiation of imatinib treatment were associated with longer PFS (P = 0.0099). According to the Sokal scoring system, the rates of MCyR and CCyR in low-risk patients were significantly higher than those in intermediate-risk and high-risk patients (P = 0.0013, P = 0.0024). Sokal score was also significantly associated with disease progression (P = 0.0467). (4) The adverse events of imatinib were moderate and tolerable. CONCLUSIONS: Treatment of CML patients in CP with imatinib can induce high hematologic, cytogenetic and molecular response and overall survival, but can not do satisfactorily for patients in AP and BC.     

Cytogenetic response as a marker of efficacy of chronic myeloid leukemia therapy with a BCR-ABL thyrosine kinase inhibitor glivek

AIM. Clinical practice with the drug glivek (imatinibe mesilate, ST1571) blocking activity of oncoprotein p210 shows that a cytogenetic response can be reached in 50-60% of patients with chronic myeloid leukemia (CML), in a late chronic phase (CP) in resistance to or intolerance of interferon alpha (IF-alpha) and in 24-43% of patients in the acceleration phase (AP). This study aimed at assessment of the rate and stability of a cytogenetic response (CR) and long-term results of survival in CML patients on glivek. MATERIAL AND METHODS. Glivek was given to 195 CML patients (median of the treatment duration was 42 months, 1-156 months, of the patients' age--46 years). 79 patients were in CP, 116--in AP. The doses were 400 mg/day and 116 mg/day, respectively. Karyotype was studied before the treatment and later after each 6 months. RESULTS: A considerable CR was achieved in 57% patients in CP and 44%--in AP. Of them complete CR was obtained in 48 and 35%, respectively. Marked CR is a favourable prognostic factor. Survival of patients with marked CR in CP (97% 0 and AP (89%) was significantly higher than without CR (58 and 47%, respectively, p < 0.05). Marked CR persisted in 95% cases in both phases of CML. In complete CR, a repeated study of karyotype revealed residual number of Ph+ cells both in CP and AP in 86% patients. This demonstrates necessity to take glivek continuously in achievement of a complete CR by karyotypic test. Glivek inhibits the disease progression, lowers annual lethality. 42-month (median of glivek treatment duration) overall survival reached 91 and 59% in CP and AP, respectively. CONCLUSION: CR is an integral index prognosticating CML course. Survival rose significantly in patients with marked CR both in CP and AP of CML. Marked CR is persistent in continuous glivek therapy. The rate of a CR depends much on the disease stage.     

Bestatin treatment of myelodysplastic syndromes and chronic myelogenous leukemia

A high remission rate (56%) was achieved in a preliminary study using Bestatin in patients with myelodysplastic syndromes. In particular, 9 out of 13 patients (69%) in the high blast group achieved hematologic remission. After Bestatin treatment, intrinsic hematopoietic stem cell abnormalities as well as hematologic findings were markedly improved. The success of Bestatin therapy in MDS led us to investigate the clinical activity of Bestatin in CML. In the current study the busulfan and Bestatin combination therapy resulted in complete hematologic remission in all of the patients. The most exciting result was the suppression of the Philadelphia chromosomes among the responding patients. Complete cytogenetic response was obtained in 3 patients (21%), partial cytogenetic response in 1 (7%), and minor cytogenetic response in 5 (36%). In particular, the majority of early chronic phase CML patients achieved significant cytogenetic response with sustained Ph1 negativity. The results are very encouraging and warrant further studies.