1099P - BCR-ABL transcript variant’s significance in chronic myeloid leukemia in chronic phase: Institutional experience from a developing country

Abstract

BackgroundChronic myeloid leukemia (CML) is a malignant clonal hematopoietic disorder characterized by a translocation between chromosomes 9 and 22 leading to the production of BCR-ABL fusion protein. This fusion produces mainly two variants, namely b3a2 and b2a2, rarely are other transcripts detected. To date, the exact role of these transcript variants are unknown and has shown mixed results. The objective of this study is to study the clinical-hematological profile and major molecular response rates (MMR) at 1 year in relation to b2a2 and b3a2 transcripts in CML-CP. MethodsAfter approval from the institutional ethics committee, the data of patients attending medical oncology department from January 2014 to December 2015 (2 years) were collected and analyzed. A total of 154 patients were diagnosed with CML and 140 of them were in chronic phase (CP). ResultsAmong 140 patients, males accounted for 88 (62%) and b3a2 type was seen in 99 patients (71%). Baseline parameters like hemoglobin, white cell count, platelet count, Sokal scoring, and EUTOS risk are shown in Table below. Follow up data was not available for 2 and 9 patients in b2a2 and b3a2 type, respectively.*SEM: Standard Error of Mean After 1 year of therapy with imatinib, 63% in b2a2 and 52% in b3a2 type achieved MMR (p-value 0.21). Twenty patients (14%) were evaluated for kinase domain resistance mutations (17 in b3a2 and 3 in b2a2). Seven out of 17 patients in b3a2 and none in b2a2 type had detectable mutations. Phase migration to accelerated or blast phase occurred in 3 (7%) and 9 (9%) in b2a2 and b3a2 transcript types, respectively.Table: 1099PTable: 1099PParameter (N=140)B2a2 (n=41)B3a2 (n=99)P valueMean Hemoglobin mg/dl SEM9.6 0.319.8 0.20.6 NSMean Total Leucocyte Count (X109) SEM166 16.3185 9.80.3 NSMean Platelet Count (X109) SEM379 3.57440 2.420.16 NSSokal risk (%) Low Intermediate High3 (7) 20 (49) 18 (44)7 (7) 40 (40) 52 (53)0.63 NSEUTOS risk (%) Low High12 (30) 29 (70)53 (52) 47 (47)0.011 SignificantMMR at 1 year (%)63520.21NS*SEM: Standard Error of Mean After 1 year of therapy with Imatinib, 63% in b2a2 and 52% in b3a2 type achieved MMR (p-value 0.21). Twenty patients (14%) were evaluated for kinase domain resistance mutations (17 in b3a2 and 3 in b2a2). Seven out of 17 patients in b3a2 and none in b2a2 type had detectable mutations. Phase migration to accelerated or blast phase occurred in 3 (7%) and 9 (9%) in b2a2 and b3a2 transcript types respectively. ConclusionsThere is no statistically significant difference between the two transcripts in relation to baseline hematological parameters. Patients with b2a2 type had higher EUTOS score at presentation. Despite this, at the end of 12 months, MMR rates were similar between b2a2 and b3a2 transcript types. Legal entity responsible for the studySiva K Prasad. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.