Higashi Takehiro, Tsukada Junichi, Kato Chiaki, Iwashige Atsushi, Mizobe Takamitsu, Machida Shinichiro, Morimoto Hiroaki, Ogawa Ryosuke, Toda Yoko, Tanaka Yoshiya
First Department Internal Medicine, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan.
Am J Hematol. 2004 Jul;76(3):275-8. doi: 10.1002/ajh.20096.
Although imatinib mesylate has shown encouraging activity in chronic myelogenous leukemia (CML), disease progression during therapy has been observed, manifested by clonal expansion of imatinib mesylate-resistant leukemia cells. On the other hand, myelosuppression related to treatment of imatinib mesylate is often managed with temporary interruption of treatment or dose reduction. We here report two CML patients who had imatinib mesylate-sensitive blast crisis (BC) immediately after discontinuation of imatinib mesylate therapy. The patients discontinued therapy because of neutropenia. Although there was no evidence of blastic phase during therapy, BC occurred 2 weeks after the withdrawal of treatment in both cases. Interestingly, additional chromosomal abnormalities were detected following the withdrawal of imatinib mesylate and disappeared by re-introduction of this agent. The same doses of imatinib mesylate was still effective and remission was sustained with imatinib mesylate alone again. Our report suggests the possibility that withdrawal of imatinib mesylate may lead to proliferation of blast clones even in patients showing good responses to imatinib mesylate without signs of disease progression.
尽管甲磺酸伊马替尼在慢性髓性白血病(CML)中已显示出令人鼓舞的活性,但在治疗期间已观察到疾病进展,表现为甲磺酸伊马替尼耐药白血病细胞的克隆性扩增。另一方面,与甲磺酸伊马替尼治疗相关的骨髓抑制通常通过暂时中断治疗或降低剂量来处理。我们在此报告两名CML患者,他们在停用甲磺酸伊马替尼治疗后立即出现对甲磺酸伊马替尼敏感的急变期(BC)。患者因中性粒细胞减少而停止治疗。尽管在治疗期间没有急变期的证据,但在两例患者中,停药2周后均发生了BC。有趣的是,停用甲磺酸伊马替尼后检测到额外的染色体异常,重新引入该药物后这些异常消失。相同剂量的甲磺酸伊马替尼仍然有效,再次单独使用甲磺酸伊马替尼可维持缓解。我们的报告提示,即使在对甲磺酸伊马替尼反应良好且无疾病进展迹象的患者中,停用甲磺酸伊马替尼也可能导致原始克隆的增殖。