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The BCR‐ABL1 transcript type influences response and outcome in P hiladelphia chromosome‐positive chronic myeloid leukemia patients treated frontline with imatinib
Author(s) -
Castagnetti Fausto,
Gugliotta Gabriele,
Breccia Massimo,
Iurlo Alessandra,
Levato Luciano,
Albano Francesco,
Vigneri Paolo,
Abruzzese Elisabetta,
Rossi Giuseppe,
Rupoli Serena,
Cavazzini Francesco,
Martino Bruno,
Orlandi Ester,
Pregno Patrizia,
Annunziata Mario,
Usala Emilio,
Tiribelli Mario,
Sica Simona,
Bonifacio Massimiliano,
Fava Carmen,
Gherlinzoni Filippo,
Bocchia Monica,
Soverini Simona,
Bochicchio Maria Teresa,
Cavo Michele,
Giovanni Martinelli,
Saglio Giuseppe,
Pane Fabrizio,
Baccarani Michele,
Rosti Gianantonio
Publication year - 2017
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.24774
Subject(s) - medicine , imatinib , myeloid leukemia , oncology , surgery
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 MR 3.0 (6 and 12 months) and MR 4.0 (41 and 61 months) was significantly shorter for e14a2 patients compared to e13a2 patients, with a higher cumulative probability of MR 3.0 (88% and 83%, P < .001) and MR 4.0 (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.