甲磺酸伊马替尼治疗Ph阳性慢性髓性白血病慢性期引起的血细胞减少与遗传学疗效的关系

Relationship between cytopenia and cytogenetic response in imatinib mesylate treated Ph-positive chronic myeloid leukemia in chronic phase patients

目的 :探讨甲磺酸伊马替尼治疗Ph阳性慢性髓性白血病 (chronicmyeloidleukemia ,CML)慢性期引起的血细胞减少与遗传学疗效的关系。方法 :5 4例CML慢性期患者 ,日服伊马替尼 4 0 0或 60 0mg ,持续 18个月。结果 :伊马替尼治疗初期 2个月 ,患者严重的白细胞减少 (白细胞 <2 .0× 10 9L-1)、贫血 (血红蛋白 <10 0 g·L-1)和严重的血小板减少 (血小板 <5 0× 10 9L-1)的发生率分别为 14 .8%、3 7.0 %和 2 7.8% ,多数可自行恢复 ,少数出现严重的白细胞 /血小板减少者需要减量或中断治疗。患者治疗前血红蛋白越低、血小板越高 ,治疗中白细胞和血红蛋白谷值越低 ;治疗前血小板越低 ,治疗中血小板谷值越低。严重的白细胞及血小板减少的危险因素分别为 :治疗前血小板≥ 5 0 0× 10 9L-1和外周血嗜碱细胞≥ 5 %及治疗前血小板 <10 0× 10 9L-1和外周血嗜碱细胞≥ 5 %。伊马替尼治疗 1年中 ,出现严重的白细胞减少者在治疗各期、出现贫血者在治疗 6个月内、出现严重的血小板减少者在治疗 3个月时获得的遗传学效应均显著降低。结论 :血细胞减少是伊马替尼治疗CML慢性期比较常见的毒副作用 ,出现严重的白细胞减少与持久获得较低的遗传学疗效显著相关 ,出现贫血和严重的血小板减少与治疗早期 (6个月内 )获得较低的遗传?

Objectives: To evaluate the relationship between cytopenia and cytogenetic response in Imatinib mesylate treated Ph positive chronic myeloid leukemia (CML) in chronic phase patients. Methods: Fifty four patients with Ph+CML in chronic phase received oral administration of Imatinib 400 or 600 mg once a day for 18 months. Results:In the early phase of Imatinib treatment, rates of severe leukopenia (leukocyte <2.0×10 9 L -1 ), anemia (hemoglobin <100 g·L -1 ) and severe thrombocytopenia (platelet <50×10 9 L -1 ) were 14.8%, 37.0% and 27.8%, respectively. Hemocytes recovered in most patients with continued therapy. Treatment was interrupted or dosage reduced in a few patients. The lower the hemoglobin and higher the platelet before the regime, the lower the nadir of leukocytes and hemoglobin counts during the treatment. The lower the platelet count before the regime, the lower the nadir of platelets during the treatment. Risk factors for severe leukopenia were thrombocytosis (≥500×10 9 L -1 ) and basophilia ≥5% before the treatment. Risk factors for severe thrombocytopenia were thrombocytopenia (<100×10 9 L -1 ) and basophilia ≥5% before the treatment. During the 12 month treatment with Imatinib, the statistically significant lower probabilities of cytogenetic response were observed at all checked points in patients with severe leukopenia, at the end of 3 and 6 months in patients with anemia, at the end of 3 months in patients with severe thrombocytopenia. Conclusion: Cytopenia is a common side effect in patients with CML in chronic phase treated with Imatinib mesylate. Severe leukopenia is associated with a sustained lower major cytogenetic response, whereas anemia and severe thrombocytopenia influence more for the first 6 months.