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Early response does not predict outcome in children and adolescents with chronic myeloid leukaemia treated with high‐dose imatinib
Author(s) -
Giona Fiorina,
Saglio Giuseppe,
Santopietro Michelina,
Menna Giuseppe,
Putti Maria Caterina,
Micalizzi Concetta,
Iaria Grazia,
Santoro Nicola,
Ladogana Saverio,
Mura Rosamaria,
Burnelli Roberta,
Consarino Caterina,
Cosmi Carlo,
Moleti Maria Luisa,
Leszl Anna,
Tucci Francesca,
Nanni Mauro,
Diverio Daniela,
Biondi Andrea,
Locatelli Franco,
Foà Robin
Publication year - 2018
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.14458
Subject(s) - imatinib , medicine , imatinib mesylate , cohort , chronic myeloid leukaemia , oncology , myeloid leukemia , gastroenterology , immunology
The achievement of early response has been shown to predict a significantly better outcome in adults with chronic myeloid leukaemia (CML) in chronic phase (CP) treated with either imatinib (IM) or second-generation tyrosine kinase inhibitors (TKIs) (Branford et al, 2012; Hanfstein et al, 2012; Marin et al, 2012; Jain et al, 2013; Jabbour et al, 2014). Recently, early molecular response (EMR) was also reported to predict a better outcome in 40 CP-CML children treated with IM at a standard dose (260 mg/m/day) (Millot et al, 2014). We hereby analysed the predictive value of the BCR-ABL1 transcript levels at 3 months in terms of responses and outcome in a cohort of children and adolescents with CP-CML treated with high-dose IM at 11 Italian centres. This study (CMLPetit-01) was approved by the Institutional Ethics Committees. From March 2001 to March 2014, 53 patients younger than 18 years of age with a newly diagnosed CML in CP were treated with IM at a dose of 340 mg/m/day. Cytogenetics and quantitative reverse transcription polymerase chain reaction (qPCR) analysis were planned on bone marrow (BM) every 3 months and qPCR on peripheral blood (PB) monthly, as previously described (Giona et al, 2015). Haematological and cytogenetic response (CyR) criteria were defined according to the European LeukaemiaNet recommendations (Baccarani et al, 2009). Major molecular response (MMR) was defined as ≤0 1% BCR-ABL1 according to the International Scale (IS), while molecular response (MR) was considered as ≤0 01% BCR-ABL1 IS. Complete molecular response (CMR) was used to indicate levels of disease ≤0 0032% BCR-ABL1 IS or undetectable. Transcript levels ≤10% and ≤1% BCR-ABL1 IS at 3 months after starting IM were defined as EMR and deep EMR, respectively. Forty-four CP-CML patients (27 males, 17 females; median age: 11 years, range 3 to 15) who had available BCR-ABL1 levels at 3 months and had been followed for at least 12 months were included in this analysis. Overall, 92 5%, 85%, 56% and 39% of patients achieved a complete CyR (CCyR), MMR, MR and CMR after a median time of 6 2 (range 3 5–8 6), 13 4 (range 9 4–19 7), 14 9 (range 10 1– 24 1) and 15 (range 10 1–24 8) months, respectively. Three months after the start of IM, BCR-ABL1 transcript levels >10% IS were detected in 9/44 (20 5%) patients, whereas 18/ 44 (41%) and 17/44 (38 5%) patients had BCR-ABL1 IS of