Sawyers Charles L, Hochhaus Andreas, Feldman Eric, Goldman John M, Miller Carole B, Ottmann Oliver G, Schiffer Charles A, Talpaz Moshe, Guilhot Francois, Deininger Michael W N, Fischer Thomas, O'Brien Steve G, Stone Richard M, Gambacorti-Passerini Carlo B, Russell Nigel H, Reiffers Jose J, Shea Thomas C, Chapuis Bernard, Coutre Steven, Tura Sante, Morra Enrica, Larson Richard A, Saven Alan, Peschel Christian, Gratwohl Alois, Mandelli Franco, Ben-Am Monique, Gathmann Insa, Capdeville Renaud, Paquette Ronald L, Druker Brian J
Department of Medicine and Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA.
Blood. 2002 May 15;99(10):3530-9. doi: 10.1182/blood.v99.10.3530.
Blast crisis is the most advanced stage of chronic myelogenous leukemia (CML) and is highly refractory to therapy. CML is caused by expression of the chimeric BCR-ABL tyrosine kinase oncogene, the product of the t(9;22) Philadelphia translocation. Imatinib (Glivec, formerly STI571) is a rationally developed, orally administered inhibitor of the Bcr-Abl tyrosine kinase. A total of 260 patients with CML were enrolled in a phase II trial, of whom 229 had a confirmed diagnosis of CML in blast crisis. Patients were treated with imatinib in daily oral doses of 400 mg or 600 mg. Imatinib induced hematologic responses in 52% of patients and sustained hematologic responses lasting at least 4 weeks in 31% of patients, including complete hematologic responses in 8%. For patients with a sustained response, the estimated median response duration was 10 months. Imatinib induced major cytogenetic responses in 16% of patients, with 7% of the responses being complete. Median survival time was 6.9 months. Nonhematologic adverse reactions were frequent but generally mild or moderate. Episodes of severe cytopenia were also frequent and were attributable to the underlying condition and treatment with imatinib. Drug-related adverse events led to discontinuation of therapy in 5% of patients, most often because of cytopenia, skin disorders, or gastrointestinal reactions. These results demonstrate that imatinib has substantial activity and a favorable safety profile when used as a single agent in patients with CML in blast crisis. Additional clinical studies are warranted to explore the efficacy and feasibility of imatinib used in combination with other antileukemic drugs.
急变期是慢性粒细胞白血病（CML）的最晚期阶段，对治疗高度耐药。CML由嵌合型BCR-ABL酪氨酸激酶致癌基因的表达引起，该基因是t(9;22)费城染色体易位的产物。伊马替尼（格列卫，原STI571）是一种经合理研发的口服BCR-Abl酪氨酸激酶抑制剂。共有260例CML患者参加了一项II期试验，其中229例确诊为CML急变期。患者接受伊马替尼治疗，每日口服剂量为400mg或600mg。伊马替尼使52%的患者出现血液学反应，31%的患者出现持续至少4周的持续血液学反应，其中8%为完全血液学反应。对于有持续反应的患者，估计中位反应持续时间为10个月。伊马替尼使16%的患者出现主要细胞遗传学反应，其中7%为完全反应。中位生存时间为6.9个月。非血液学不良反应常见，但一般为轻度或中度。严重血细胞减少事件也很常见，可归因于基础疾病和伊马替尼治疗。与药物相关的不良事件导致5%的患者停药，最常见的原因是血细胞减少、皮肤疾病或胃肠道反应。这些结果表明，伊马替尼作为单一药物用于CML急变期患者时具有显著活性和良好的安全性。有必要进行更多的临床研究来探索伊马替尼与其他抗白血病药物联合使用的疗效和可行性。
