伊马替尼联合干扰素-α治疗慢性髓性白血病的回顾性研究

A retrospective study of chronic myelocytic leukemia treatment with imatinib and interferon-α

目的探讨联合应用伊马替尼和IFN-α治疗慢性髓性白血病（CML）的临床效果。方法选择155例CML慢性期患者为研究对象，根据治疗方法分为伊马替尼组和伊马替尼联合INF-α组，观察并比较两组患者的完全细胞遗传学反应率（CCyR）、主要分子学反应率（MMR）和完全分子学反应率（CMR）以及总体生存（OS）率、无进展生存（PFS）率。结果在用药6个月时联合组的CCyR率高于伊马替尼组（60．6％对41．6％，P〈0．05），从12个月时开始差异无统计学意义。用药6个月和12个月时联合组的MMR＋CMR率高于伊马替尼组（71．2％对34．8％，77．3％对52．8％，P〈0．05），从24个月时开始差异无统计学意义。根据Sokal积分进行风险分层后，低、中危患者的CCyR率在6个月时联合组均高于伊马替尼组（77．8％对52．6％，75．0％对46．7％，P〈0．05），从12个月开始差异无统计学意义；低、中危患者的MMR＋CMR率在6和12个月时联合组均高于伊马替尼组（6个月：85．2％对36．8％，90．0％对36．7％，P〈0．05；12个月：88．9％对57．9％，90．0％对56．7％，P〈0．05），从24个月时开始差异无统计学意义，而两组高危患者之间差异一直无统计学意义。伊马替尼组和联合组在用药6、12、24和36个月时的OS率分别为100％、100％、96．8％、90．0％和100％、100％、97．9％、93．1％，PFS率分别为97．8％、95．5％、91．9％、85．5％和98．5％、95．5％、91．5％、86．2％，OS率（u=0．427，P=0．514）、PFS率（／Z=0．556，P=0．456）两组差异无统计学意义。两组常见不良反应均有血细胞减少、水肿、体重增加、骨痛、皮疹和肌肉痉挛，联合组还有流感症状、肝功能损伤、甲状腺功能异常和肢体感觉障碍等，联合组有Ⅲ、Ⅳ级血细胞减少发生率增加的趋势。结论联合应用伊马替尼和IFN—α能够更快地获得细胞遗传学反应和分子学反应，尤其对于低、中危患者，而高危患者联合用药无明显意义。在用药36个月内，联合用药并未明显提高生存率，且有增加药物不良反应的可能。

Objective To investigate the clinical effect of chronic myelocytie leukemia （CML） patients treated with imatinib （IM） and interferon （IFN） -α. Methods One hundred and fifty five CML patients at chronic phase were included in the study. All patients were divided into two groups according to treatment regimen： IM ＋ IFN group and IM group. Complete eytogenetic response （CCyR） rate, major molecular response （MMR） rate, complete molecular response （CMR） rate, overall survival （OS） and progression free survival （PFS） were observed and compared in both groups. Results The CCyR rate was higher in the IM ＋ IFN group than that in the IM group at 6 months （60.6% vs 41.6 %, P 〈 0.05 ） , hut no difference was observed later on. The MMR ＋ CMR rate was higher in the IM ＋ IFN group than that in the IM group at 6 months and 12 months（71.2% vs 34.8%, 77.3% vs 52.8% , respectively, P 〈 0.05 ）, but no difference after that. After stratification according to Sokal risk, the CCyR rate of low- and intermediate-risk patients was higher in the IM ＋ IFN group than that in the IM group at 6 months （77.8% vs 52.6%, 75.0% vs 46.7%, P 〈 0.05 ） , but not from 12 months on ; the MMR ＋ CMR rate of low- and intermediate-risk patients was higher in the IM ＋ IFN group than that in the IM group at 6 months and 12 months （85.2% vs 36.8%, 90.0% vs 36.7%, P〈0.05; 88.9% vs57.9%, 90.0% vs56.7%, P〈0.05）, but not from 24 months on. There was no significant difference in high-risk patients. OS in IM and IM ＋ IFN group at 6, 12, 24 and 36 months was 100% , 100% , 96.8% and 90.0%, and 100% , 100% , 97.9% and 93.1% , respectively. PFS in IM and IM ＋ IFN group at 6, 12, 24 and 36 months was 97.8%, 95.5%, 91.9% and 85.5% , and 98.5% ,95.5% , 91.5% and 86.2% , respectively. There was no significant difference in OS （ u = 0. 427, P = 0. 514） or PFS （u =0. 556, P =0. 456）. The side effects in both groups included pancytopenia, edema, weight gain, ostalgia, rash and muscle spasm. In addition, patients in the IM ＋ IFN group suffered from flulike symptoms, impaired liver function, abnormal thyroid function and extremity sensory disturbance. It seemed that grade HI or IV pancytopenia occurred more commonly in the patients in the IM ＋ IFN group, however, there was no statistically significance. Conclusions The response to IM ＋ IFN is more rapid than that to IM alone, especially for the low- and intermediate-risk patients. It seems no benefit of the addition of IFN to treatment of high-risk patients. During the period of 36 months, survival rate in the IM ＋ IFN group is not higher than that in IM group, and it is possible to increase the side effects of pharmaceutical drugs.