A69
BCR-ABL mutation a tool for imatinib resistance in chronic myeloid leukemia patients
AB Rashid Mir, Sudha Sazawal, Rekha Chobey, Bharti sharma, Renu Saxena
All India Institute of Medical Sciences, New Dehli, India
Background
India is a developing country, so chronic myeloid leukemia (CML) patients cannot afford expensive tests like sequencing for BCR-ABL mutation. We therefore standardized ASO-PCR for routine screening of T315I mutations.
Aims
The aims were: to detect BCR-ABL mutation (T315I) and study its role in Imatinib failure in CML patients; and to study prevalence of T315I mutation in our relapsed CML patients.
Method
CML patients were diagnosed by RT-PCR and treated with Imatinib mesylate (400mg/day) as frontline therapy. All 200 CML patients on imatinib therapy were screened for T315I mutation by ASO-PCR and were evaluated for hematologic and molecular responses, time to progression, survival and toxicity.
Results
45/200 lost imatinib response after three years and 10 were already in advanced disease. 37 /45 (who had lost imatinib response) were positive for T315I mutation and 8/10 cases (AP/BC-CML) were positive for T315I mutation. All patients with T315I (+) showed poor prognosis and rapid progression to advanced disease. Five patients died.T315I was reported in 80% of relapsed cases. Survival and time-to-progression curves were obtained from Kaplan-Meier method. Prevalence of T315I mutations: 20 to 25%
Conclusion
The early detection of T315I by ASO-PCR assay proved to be helpful in clinical management of therapeutic decisions in relapsed CML patients. ASO-PCR proved to be economical, sensitive and a rapid technique for detection of T315I mutation.
