甲磺酸伊马替尼治疗费城染色体阳性、加速期慢性粒细胞白血病

Treatment of philadelphia chromosome-positive, accelerated-phase chronic myelogenous leukemia with imatinib mesylate.

作者信息

Kantarjian Hagop M, O'Brien Susan, Cortes Jorge E, Smith Terry L, Rios Mary Beth, Shan Jianqin, Yang Ying, Giles Francis J, Thomas Deborah A, Faderl Stefan, Garcia-Manero Guillermo, Jeha Sima, Wierda William, Issa Jean-Pierre J, Kornblau Steven M, Keating Michael, Resta Debra, Capdeville Renaud, Talpaz Moshe

机构信息

Departments of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.

出版信息

Clin Cancer Res. 2002 Jul;8(7):2167-76.

PMID:12114417

Abstract

PURPOSE

Imatinib mesylate, a specific Bcr-Abl tyrosine kinase inhibitor, has shown encouraging activity in chronic myelogenous leukemia (CML).

EXPERIMENTAL DESIGN

We treated 237 patients (median age, 50 years; age range, 18-82 years) with Philadelphia chromosome (Ph)-positive accelerated-phase CML with oral imatinib mesylate at daily doses of 400 mg (26 patients) or 600 mg (211 patients) and evaluated response and survival characteristics in univariate and multivariate analyses.

RESULTS

Among the 200 patients with accelerated-phase CML for whom follow-up was 3 months or more, rates of complete and partial hematological response were 80% and 10%. Cytogenetic responses were evident in 90 patients [45%; complete response in 47 patients (24%) and partial response (Ph 1-34%) in 21 patients (11%)]. The estimated 18-month survival rate was 73%. The estimated complete hematological response rate at 18 months was 68%; that for cytogenetic response was 82%. In multivariate analyses, a diagnosis-to-treatment interval of 3 years or more, splenomegaly, and peripheral blasts predicted poor major cytogenetic response; age >60 years, marrow basophilia, and clonal evolution predicted poor survival. The 600-mg drug dose was associated with better cytogenetic response and survival in univariate analysis (P < 0.01) but not in multivariate analysis. Landmark analysis showed that achieving a cytogenetic response at 3 months or a major cytogenetic response (Ph < 35%) at 6 months was associated with better long-term survival. Seven of 15 patients who were in a second chronic phase achieved major cytogenetic response. The incidence of severe nonhematological toxic effects was 23%; drug discontinuation for severe toxicity was needed in 3% of patients.

CONCLUSIONS

Imatinib mesylate was active against Ph-positive, accelerated-phase CML, and the prognostic factors identified in this study could aid in tailoring treatment strategies to specific risk groups.

摘要

目的

甲磺酸伊马替尼是一种特异性Bcr - Abl酪氨酸激酶抑制剂，在慢性粒细胞白血病（CML）中已显示出令人鼓舞的活性。

实验设计

我们用甲磺酸伊马替尼口服治疗237例费城染色体（Ph）阳性的加速期CML患者（中位年龄50岁；年龄范围18 - 82岁），每日剂量为400 mg（26例患者）或600 mg（211例患者），并在单因素和多因素分析中评估反应和生存特征。

结果

在200例随访3个月或更长时间的加速期CML患者中，完全血液学反应率和部分血液学反应率分别为80%和10%。90例患者出现细胞遗传学反应[45%；47例患者（24%）完全反应，21例患者（11%）部分反应（Ph 1 - 34%）]。估计18个月生存率为73%。估计18个月时的完全血液学反应率为68%；细胞遗传学反应率为82%。在多因素分析中，诊断至治疗间隔3年或更长、脾肿大和外周血原始细胞提示主要细胞遗传学反应不良；年龄>60岁、骨髓嗜碱性粒细胞增多和克隆演变提示生存不良。在单因素分析中，600 mg药物剂量与更好的细胞遗传学反应和生存相关（P < 0.01），但在多因素分析中并非如此。标志性分析表明，3个月时达到细胞遗传学反应或6个月时达到主要细胞遗传学反应（Ph < 35%）与更好的长期生存相关。15例处于第二次慢性期的患者中有7例达到主要细胞遗传学反应。严重非血液学毒性反应的发生率为23%；3%的患者因严重毒性需要停药。