Braziel Rita M, Launder Teresa M, Druker Brian J, Olson Susan B, Magenis R Ellen, Mauro Michael J, Sawyers Charles L, Paquette Ronald L, O'Dwyer Michael E
Dept of Pathology, Oregon Health Sciences University, Portland, OR 97201, USA.
Blood. 2002 Jul 15;100(2):435-41. doi: 10.1182/blood.v100.2.435.
Imatinib mesylate, an Abl kinase inhibitor, produces sustained complete hematologic responses (CHRs) in chronic myelogenous leukemia (CML) patients, but the sequence and timing of morphologic and cytogenetic changes in CML patients during prolonged imatinib mesylate treatment has not been described. In this report, we document sequential hematologic and bone marrow findings in 19 interferon-refractory/interferon-intolerant chronic phase CML patients on imatinib mesylate for at least 14 months. Patients treated at an effective oral dose (300 to 600 mg per day) were followed with peripheral blood (PB) counts, marrow examination, and cytogenetic studies at 0, 2, 5, 8, 11, and 14 months. By 2 months, 17 of 19 patients achieved CHR; 1 reached CHR by 5 months, and 1 at 11 months. Five of 19 patients developed cytopenias requiring treatment interruption and/or dose reduction, but all were able to continue in CHR on study. In contrast to interferon-alfa treatment, imatinib mesylate-treated CML patients achieved not only CHR but complete morphologic marrow response. Normalization of marrow lagged behind PB response; however, by 8 months, all marrows showed normal or reduced cellularity without morphologic evidence of CML. Eighteen of 19 patients continued in CHR and morphologic marrow remission at 14 months; 1 patient relapsed with chronic phase CML. Although hematologic and marrow responses were uniform, cytogenetic responses were variable. Complete cytogenetic responses occurred in 6 patients, with 4 also in remission by fluorescent in situ hybridization and/or reverse-transcription-polymerase chain reaction. Six of 19 had partial and 7 of 19 no cytogenetic response. Several patients acquired additional clonal cytogenetic abnormalities during therapy, a finding with significant implications for prognosis and laboratory monitoring in imatinib mesylate-treated CML patients.
甲磺酸伊马替尼是一种Abl激酶抑制剂，可使慢性髓性白血病（CML）患者产生持续的完全血液学缓解（CHR），但长期接受甲磺酸伊马替尼治疗的CML患者形态学和细胞遗传学变化的顺序和时间尚未见报道。在本报告中，我们记录了19例对干扰素耐药/不耐受的慢性期CML患者接受甲磺酸伊马替尼治疗至少14个月后的血液学和骨髓检查结果。接受有效口服剂量（每日300至600 mg）治疗的患者在第0、2、5、8、11和14个月时进行外周血（PB）计数、骨髓检查和细胞遗传学研究。到2个月时，19例患者中有17例实现了CHR；1例在5个月时达到CHR，1例在11个月时达到CHR。19例患者中有5例出现血细胞减少，需要中断治疗和/或降低剂量，但所有患者在研究中均能继续保持CHR。与干扰素-α治疗不同，接受甲磺酸伊马替尼治疗的CML患者不仅实现了CHR，还实现了完全的形态学骨髓缓解。骨髓正常化滞后于PB反应；然而，到8个月时，所有骨髓均显示细胞数量正常或减少，无CML的形态学证据。19例患者中有18例在14个月时继续保持CHR和形态学骨髓缓解；1例患者慢性期CML复发。尽管血液学和骨髓反应是一致的，但细胞遗传学反应是可变的。6例患者出现完全细胞遗传学反应，其中4例通过荧光原位杂交和/或逆转录-聚合酶链反应也处于缓解状态。19例中有6例出现部分细胞遗传学反应，7例无细胞遗传学反应。几名患者在治疗期间获得了额外的克隆性细胞遗传学异常，这一发现对接受甲磺酸伊马替尼治疗的CML患者的预后和实验室监测具有重要意义。
