Study on Mutation Resistance to Imatinib in Chronic Myeloid Leukemia Patients from West India

A. Darji, P. Bharadia
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Abstract

Imatinib is a type of protein tyrosine kinase inhibitor which inhibits the constitutive abnormal tyrosine kinase created by the Philadelphia chromosome i.e. the BCR-ABL tyrosine kinase, abnormality in CML patient. The aim of the study is to assess the response of imatinib in CML patients and to observe resistance to imatinib. Study was performed at Ahmedabad, Gujarat, India. Dose of 400, 600, 800 mg of Imatinib was found to be prescribed to all patients during the study. Comparison of laboratory parameters and PCR data were done after measurement by RT-PCR method. Total 256 patients with CML were enrolled in the study. 196 patients had completed study as per protocol. 38 patients were newly diagnosed whereas 158 patients were already diagnosed with CML. 89.29% (n = 175) of patients achieved complete haematological response, Complete MolR were achieved in n = 41 at 6th months, n = 1 at 12th month & 18th month and no patient was found with none CyR out of 196 patients; no patient were found with minimal CyR at 6th month, 2 patient were at 12th month and 3 patients were at 18th month. Mean PCR value (BCR-ABL/ABL ratio) in patient was found 0.245±1.16 at Day 0, 0.824±1.51 at 6th month, 4.086±9.58 at 12th month and 6.713±11.32 at 18th month visit. In conclusion, it was observed that resistance to imatinib might be developed within an average time of 12 months in the patients due to which survival rate was drastically reduced.
西印度慢性髓系白血病患者对伊马替尼的突变耐药研究
伊马替尼是一种蛋白酪氨酸激酶抑制剂,抑制由费城染色体产生的组成型异常酪氨酸激酶,即CML患者异常的BCR-ABL酪氨酸激酶。该研究的目的是评估伊马替尼对CML患者的疗效,并观察对伊马替尼的耐药性。研究在印度古吉拉特邦的艾哈迈达巴德进行。在研究期间,发现所有患者的伊马替尼剂量分别为400,600,800mg。采用RT-PCR法测定后,将实验室参数与PCR数据进行比较。共有256例CML患者参加了这项研究。196例患者按照方案完成了研究。38例新诊断,158例已诊断为CML。89.29% (n = 175)的患者获得完全血液学缓解,在6个月时达到完全MolR的患者有41例,在12个月和18个月时达到完全MolR的患者有1例,196例患者中无CyR;6个月无患者出现最小CyR, 12个月2例,18个月3例。患者第0天的平均PCR值(BCR-ABL/ABL比值)为0.245±1.16,第6个月为0.824±1.51,第12个月为4.086±9.58,第18个月为6.713±11.32。综上所述,观察到患者在平均12个月的时间内可能产生对伊马替尼的耐药,从而大大降低了生存率。
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