Impact of BCR-ABL Transcript Subtypes in Achieving Major Molecular Remission in Chronic Phase, Chronic Myeloid Leukemia Treated with Tyrosine Kinase Inhibitors

Introduction:

The most common BCR-ABL transcripts are e13a2 (b2a2) and e14a2 (b3a2) reflecting different breakpoints in the BCR gene on chromosome 22. Clinically, their prognostic significance is unclear. Conflicting data exists regarding inferior outcomes in patients expressing e13a2 transcripts. Therefore, we conducted a retrospective study to determine the impact of these transcripts in chronic phase CML patients.

Materials and Methods:

All consecutive patients with chronic phase CML treated with tyrosine kinase inhibitors at Abington Memorial Hospital were reviewed. Patients expressing e1a2 transcript were excluded. A total of 43 patients were enrolled. Data on demographics, baseline disease characteristics, BCR-ABL subtype, response to TKI as measured by reverse transcription-polymerase chain reaction and outcomes were recorded. Besides descriptive statistics, χ² and Kaplan-Meier tests were used for data analysis.

Results:

There were 14 (39.5%) males and 26 (60.5%) females in this study (n = 43). Median age at diagnosis was 60 years (range, 20-87). At diagnosis, median WBC and platelet counts were 50.6 x 10³ per µL (range, 2-505) and 269 x 10³ per µL (range, 48-1740), respectively. Sokal score was low in 12 (30%), intermediate in 21 (49%) and high in 8 (19%) patients. Thirty-four (72%) patients expressed e13a2, 6 (13%) expressed e14a2 and 7 (15%) co-expressed both. Different TKI modalities included imatinib (n = 11, 23%), dasatinib (n = 18, 38%) nilotinib (n = 14, 30%), bosutinib (n = 2, 4%) and ponatinib (n = 2, 4%). The proportion of patients expressing e13a2, e14a2 and both achieving major molecular remission respectively at 3 months was 26.4%, 0% and 0%, 6 months was 52.9%, 50% and 14.3%, and 12 months was 58.8%, 67% and 28.5%. The proportion of patients expressing e13a2, e14a2 or both who achieved major molecular remission at 12 months was 18 (53%), 4 (67%) and 3 (43%), respectively. Estimated overall survival was not different between cohorts expressing e13a2, e14a2 and both (p value = 0.413).

Conclusion:

In this study, we did not find any difference in outcomes in patients with CML expressing e13a2, e14a2 or both. Even though patients expressing e13a2 achieved faster remissions, overall survival was the same in all cohorts. Future studies are needed to further evaluate the prognostic impact of various BCR-ABL transcripts in CML patients.