Does BCR-ABL transcript type predict cytogenetic response to imatinib mesylate in chronic phase, chronic myeloid leukemia patients?

Abstract

7043 Background: We prospectively studied BCR-ABL transcript type (b2a2, b3a2, e1a2 and e19a2 in 100 CML-CP patients treated with Imatinib mesylate therapy and studied their correlation with the cytogenetics responses. Methods: Between Aug, 2004 and Sep, 2006, 100 CML –CP patients (median age was 32 years, range, 11 to 62 years, M: F: 2.5: 1) were treated prospectively with imatinib mesylate 400 mg daily on outpatients. 70 patients were pre-treated with interferon Alfa. The mean duration of Gleevec treatment was 24 months (range 3 to 38 months). Patients were monitored closely for clinical, hematological, cytogenetic & molecular response as per standard guidelines. Bone marrow was studied at 3, 6, 9 then 4–6 months interval for cytogenetic response (CGR) and also for the presence of BCR-ABL transcript types by multiplex and nested RT-PCR technique. Results: 96% of patients achieved complete hematological remission (CHR); median time being 21 days, ranging from 7 to 110 days. 60% of patients achieved Major CGR (complete 32, partial CGR-28); median time 8 months, ranging from 6 to 22 months. Previously untreated patients had higher major (70% vs 55.7%) and complete (46.6% vs 25.7%) CGR compared to patients previously treated with interferon alfa. Analysis for BCR-ABL transcript type revealed - b2a2 in 38%, b3a2 -54% and both in 8% of patients. 28 of 38(74%) patients with b2a2 type acieved Major CGR compared to 24 of 54 (44%) patients with b3a2 transcript, p<0.002. Of remaining 40 patients with minor or no CGR, 10(25%) had b2a2 compared to 30 (75 %) b3a2 type, p<.002. However, there was no significant correlation between transcript type and pre-treatment characteristics e.g. spleen size (in cm), Hb (G/dl), WBC & platelets counts. Conclusions: Present study suggests that site of breakpoint in major breakpoint cluster region might be predictive of cytogenetic responses to Imatinib Mesylate in CML patients. No significant financial relationships to disclose.