Contributions
Abstract: PB1515
Type: Publication Only
Session title: Chronic myeloid leukemia - Clinical
Background
Most patients with Chronic Myeloid Leukemia (CML) express the BCR-ABL fusion gene that generates a 210 kDa/p210 tyrosine kinase protein that promotes leukemic metamorphosis. P210 is encoded by both transcripts that are created when the breakpoint in the BCR gene occurs in a region called M-bcr, leading to the formation of the transcripts e13a2/ “b2a2” and e14a2/ “b3a2”. The difference of both e13a2 and e14a2 transcripts is the absence and presence of exon 14 of the BCR gene respectively. The different effect of e13a2 and e14a2 transcripts on leukemic phenotype and disease outcome has been debated for many years.
Aims
The purpose of this retrospective study is to investigate the impact of different transcripts on the achievement of EMR, MMR and MR4.0 in patients who received Tyrosine Kinase Inhibitor (TKI) as first line treatment from 2005 to 2020 in Greece.
Methods
This study involved 261 patients with chronic phase CML treated with TKI and assessed for response to treatment according to ELN guidelines. Transcript type was identified by RT-PCR at diagnosis. RT-qPCR standardized by the EAC (Europe Against Cancer) protocol was assessed to determine BCR-ABL levels using ABL as the reference gene. All results are expressed according to International scale / IS.
Results
168 patients with BCR-ABL known transcripts, either e13a2 or e14a2, were included in the analyses. Sixty-four (38.1%) carried the transcript e13a2, while 12 expressed also e1a2 transcript. A hundred and four patients (61.9%) carried e14a2 transcript, only two (1.2%) co-expressed e13a2, while 23 (22.1%) expressed also e1a2 transcript. Hematological parameters were comparable between patients with different transcripts. Regarding the achievement of EMR there are no data for 14 out of 64 (21.8%) and 22 out of 104 (24.15%) patients with e13a2 and e14a2 transcripts respectively. Out of the 50 with e13a2, 23 (46%) did not achieve EMR compared to 21 out of 82 (25.61%) of patients with e14a2 transcript. Data at the timepoint of MMR and MR4 achievement are available for 141 and 148 out of 168 patients respectively. Six out of 48 (12.5%) patients with e13a2 and 4 out of 93 (4.3%) patients with e14a2, and also 15 out of 52 (28.8%) with e13a2 and 13 out of 96 (13.5%) with e14a2 did not achieve MMR (p=0.0895) and MR4.0 (p=0.0288) respectively. Patients with e13a2 and e14a2 achieved MMR at an average time of 782.35 days (median 469) and 1021.9 days (median 275), respectively. MR4.0 was achieved in 1535.8 days on average (median 882.5) and 1505.63 days (median 609) for e13a2 and e14a2 respectively.
Conclusion
Our data suggest that a larger percentage of patients with e14a2 transcript achieve EMR compared to patients with e13a2 (74.4% vs 54%). More patients with e14a2 transcripts (95.7% vs 87.5%) achieve MMR in shorter time than patients with e13a2. Failure to achieve MR4.0 was observed in patients with e13a2 more commonly versus those with e14a2 transcript. The transcript could serve as a prognostic indicator and/or as a treatment selection criterion. At present the bibliographic data are contradictory and need further study. We plan to study their importance in a larger number of patients in combination with other features of the disease and the selected TKI.
Keyword(s): BCR-ABL
Abstract: PB1515
Type: Publication Only
Session title: Chronic myeloid leukemia - Clinical
Background
Most patients with Chronic Myeloid Leukemia (CML) express the BCR-ABL fusion gene that generates a 210 kDa/p210 tyrosine kinase protein that promotes leukemic metamorphosis. P210 is encoded by both transcripts that are created when the breakpoint in the BCR gene occurs in a region called M-bcr, leading to the formation of the transcripts e13a2/ “b2a2” and e14a2/ “b3a2”. The difference of both e13a2 and e14a2 transcripts is the absence and presence of exon 14 of the BCR gene respectively. The different effect of e13a2 and e14a2 transcripts on leukemic phenotype and disease outcome has been debated for many years.
Aims
The purpose of this retrospective study is to investigate the impact of different transcripts on the achievement of EMR, MMR and MR4.0 in patients who received Tyrosine Kinase Inhibitor (TKI) as first line treatment from 2005 to 2020 in Greece.
Methods
This study involved 261 patients with chronic phase CML treated with TKI and assessed for response to treatment according to ELN guidelines. Transcript type was identified by RT-PCR at diagnosis. RT-qPCR standardized by the EAC (Europe Against Cancer) protocol was assessed to determine BCR-ABL levels using ABL as the reference gene. All results are expressed according to International scale / IS.
Results
168 patients with BCR-ABL known transcripts, either e13a2 or e14a2, were included in the analyses. Sixty-four (38.1%) carried the transcript e13a2, while 12 expressed also e1a2 transcript. A hundred and four patients (61.9%) carried e14a2 transcript, only two (1.2%) co-expressed e13a2, while 23 (22.1%) expressed also e1a2 transcript. Hematological parameters were comparable between patients with different transcripts. Regarding the achievement of EMR there are no data for 14 out of 64 (21.8%) and 22 out of 104 (24.15%) patients with e13a2 and e14a2 transcripts respectively. Out of the 50 with e13a2, 23 (46%) did not achieve EMR compared to 21 out of 82 (25.61%) of patients with e14a2 transcript. Data at the timepoint of MMR and MR4 achievement are available for 141 and 148 out of 168 patients respectively. Six out of 48 (12.5%) patients with e13a2 and 4 out of 93 (4.3%) patients with e14a2, and also 15 out of 52 (28.8%) with e13a2 and 13 out of 96 (13.5%) with e14a2 did not achieve MMR (p=0.0895) and MR4.0 (p=0.0288) respectively. Patients with e13a2 and e14a2 achieved MMR at an average time of 782.35 days (median 469) and 1021.9 days (median 275), respectively. MR4.0 was achieved in 1535.8 days on average (median 882.5) and 1505.63 days (median 609) for e13a2 and e14a2 respectively.
Conclusion
Our data suggest that a larger percentage of patients with e14a2 transcript achieve EMR compared to patients with e13a2 (74.4% vs 54%). More patients with e14a2 transcripts (95.7% vs 87.5%) achieve MMR in shorter time than patients with e13a2. Failure to achieve MR4.0 was observed in patients with e13a2 more commonly versus those with e14a2 transcript. The transcript could serve as a prognostic indicator and/or as a treatment selection criterion. At present the bibliographic data are contradictory and need further study. We plan to study their importance in a larger number of patients in combination with other features of the disease and the selected TKI.
Keyword(s): BCR-ABL