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Am J Hematol. 2017 Aug;92(8):797-805. doi: 10.1002/ajh.24774. Epub 2017 May 30.

The BCR-ABL1 transcript type influences response and outcome in Philadelphia chromosome-positive chronic myeloid leukemia patients treated frontline with imatinib.

Author information

1
Institute of Hematology "L. and A. Seràgnoli", Department of Experimental, Diagnostic and Specialty Medicine, "S.Orsola-Malpighi" University Hospital, University of Bologna, Bologna, Italy.
2
Hematology Unit, Department of Cellular Biotechnologies and Hematology, "La Sapienza" University, Roma, Italy.
3
Hematology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy.
4
Hematology Unit, "Pugliese-Ciaccio" Hospital, Catanzaro, Italy.
5
Department of Hematology, University of Bari, Bari, Italy.
6
Unit of Medical Oncology, A.O.U. Policlinico "Vittorio Emanuele", University of Catania, Catania, Italy.
7
Hematology Unit, "S. Eugenio" Hospital, Roma, Italy.
8
Hematology Unit, Azienda Ospedaliera "Spedali Civili", Brescia, Italy.
9
Hematology Unit, Azienda Ospedaliero Universitaria Ospedali Riuniti, Ancona, Italy.
10
Chair of Hematology, Azienda Ospedaliero Universitaria Arcispedale S. Anna, University of Ferrara, Ferrara, Italy.
11
Hematology Unit, Azienda Ospedaliera "Bianchi-Melacrino-Morelli", Reggio Calabria, Italy.
12
Hematology Unit, "S. Matteo" University Hospital, Pavia, Italy.
13
Hematology Unit, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza, Torino, Italy.
14
Hematology Unit, "A. Cardarelli" Hospital, Napoli, Italy.
15
Hematology Unit, "A. Businco" Hospital, Cagliari, Italy.
16
Division of Hematology and BMT, Department of Experimental and Clinical Medical Sciences, Azienda Ospedaliero-Universitaria di Udine, Udine, Italy.
17
Chair of Hematology, "A. Gemelli" University Hospital, Roma, Italy.
18
Hematology Section, Department of Medicine, University of Verona, Verona, Italy.
19
Hematology Unit, "Ordine Mauriziano" Hospital, University of Torino, Torino, Italy.
20
Hematology Unit, "Ca' Foncello" Hospital, ULSS2 Marca Trevigiana, Treviso, Italy.
21
Hematology Unit, Azienda Ospedaliera Universitaria Senese, University of Siena, Siena, Italy.
22
Chair of Hematology, Department of Biochemistry and Medical Biotechnologies, "Federico II" University, Naples, Italy.
23
Department of Hematology and Oncology "L. and A. Seràgnoli", University of Bologna, Bologna, Italy.

Abstract

The most frequent BCR-ABL1 fusion transcripts in chronic myeloid leukemia (CML) are the e13a2 (b2a2) and the e14a2 (b3a2) ones. In the imatinib era few studies addressing the prognostic significance of the BCR-ABL1 transcript type in early chronic phase CML have been published. Overall, these studies suggest that in e14a2 patients the response to imatinib is faster and deeper. To evaluate if the BCR-ABL1 transcript type (e13a2 compared to e14a2) affect the response to imatinib and the clinical outcome in newly diagnosed adult CML patients, 559 patients enrolled in 3 prospective studies (NCT00514488, NCT00510926, observational study CML/023) were analyzed. A qualitative PCR was performed at baseline: 52% patients had a e14a2 transcript, 37% a e13a2 transcript, 11% co-expressed both transcripts and 1% had other rare transcripts. The median follow-up was 76 months (95% of the patients had at least a 5-year observation). The complete cytogenetic response rates were comparable in e14a2 and e13a2 patients. The median time to MR3.0 (6 and 12 months) and MR4.0 (41 and 61 months) was significantly shorter for e14a2 patients compared to e13a2 patients, with a higher cumulative probability of MR3.0 (88% and 83%, P < .001) and MR4.0 (67% and 52%, P = .001). The 7-year overall survival (90% and 83%, P = .017), progression-free survival (89% and 81%, P = .005) and failure-free survival (71% and 54%, P < .001) were significantly better in patients with e14a2 transcript. In conclusion, patients with e13a2 transcript had a slower molecular response with inferior response rates to imatinib and a poorer long-term outcome.

PMID:
28466557
DOI:
10.1002/ajh.24774
[Indexed for MEDLINE]
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