Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the philadelphia chromosome.
Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the philadelphia chromosome.
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DOI：
10.1056/nejm200104053441402
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发表时间：
2001-04-05
影响因子：
158.5
通讯作者：
Talpaz, M
中科院分区：
文献类型：
--
作者：
Druker, BJ;Sawyers, CL;Talpaz, M
背景：BCR-ABL是一种组成激活的酪氨酸激酶，是费城染色体的产物。这种酶存在于几乎所有慢性髓性白血病（CML）患者的整个病程中，在20%的急性淋巴细胞白血病（all）患者中也存在。基于该抑制剂在慢性期患者中的实质性活性，我们评估了STI571（以前称为CGP 57148B），一种BCR-ABL酪氨酸激酶特异性抑制剂，在原细胞危重期CML患者和ph染色体阳性ALL患者中的作用。方法：在这项剂量递增的初步研究中，58例患者接受STI571治疗；38例有髓细胞危象，20例有ALL或淋巴细胞危象。治疗是口服的，每日剂量从300到1000毫克不等。结果：38例成髓细胞危象表型患者中有21例（55%）出现应答；21例患者中有4例血液学完全缓解。在20例淋巴细胞危象或ALL患者中，14例（70%）有缓解，其中4例完全缓解。7例髓细胞危象患者继续接受治疗，并在开始治疗后的101至349天内保持缓解。淋巴母细胞危象（All）患者除1例外均复发。最常见的不良反应是恶心、呕吐、水肿、血小板减少和中性粒细胞减少。结论：BCR-ABL酪氨酸激酶抑制剂STI571耐受性良好，在CML和ph染色体阳性ALL的原细胞危像中具有显著活性。[J] .中华医学杂志，2001;33(4):338 - 342。版权所有(C) 2001马萨诸塞州医学协会。
Background: BCR-ABL, a constitutively activated tyrosine kinase, is the product of the Philadelphia (Ph) chromosome. This enzyme is present in virtually all cases of chronic myeloid leukemia (CML) throughout the course of the disease, and in 20 percent of cases of acute lymphoblastic leukemia (ALL). On the basis of the substantial activity of the inhibitor in patients in the chronic phase, we evaluated STI571 (formerly known as CGP 57148B), a specific inhibitor of the BCR-ABL tyrosine kinase, in patients who had CML in blast crisis and in patients with Ph-chromosome-positive ALL.Methods: In this dose-escalating pilot study, 58 patients were treated with STI571; 38 patients had myeloid blast crisis and 20 had ALL or lymphoid blast crisis. Treatment was given orally at daily doses ranging from 300 to 1000 mg.Results: Responses occurred in 21 of 38 patients (55 percent) with a myeloid-blast-crisis phenotype; 4 of these 21 patients had a complete hematologic response. Of 20 patients with lymphoid blast crisis or ALL, 14 (70 percent) had a response, including 4 who had complete responses. Seven patients with myeloid blast crisis continue to receive treatment and remain in remission from 101 to 349 days after starting the treatment. All but one patient with lymphoid blast crisis or ALL has relapsed. The most frequent adverse effects were nausea, vomiting, edema, thrombocytopenia, and neutropenia.Conclusions: The BCR-ABL tyrosine kinase inhibitor STI571 is well tolerated and has substantial activity in the blast crises of CML and in Ph-chromosome-positive ALL. (N Engl J Med 2001;344:1038-42.) Copyright (C) 2001 Massachusetts Medical Society.