A total of 156 patients (age range 1.3–18.0 years, median 13.2 years; 91 (58.3%) male) with newly diagnosed CML (N = 146 chronic phase (CML-CP), N = 3 accelerated phase (CML-AP), N = 7 blastic phase (CML-BP)) received imatinib up-front (300, 400, 500 mg/m2, respectively) within a prospective phase III trial. Therapy response, progression-free survival, causes of treatment failure, and side effects were analyzed in 148 children and adolescents with complete data. Event-free survival rate by 18 months for patients in CML-CP (median follow-up time 25 months, range: 1−120) was 97% (95% CI, 94.2−99.9%). According to the 2006 ELN-criteria complete hematologic response by month 3, complete cytogenetic response (CCyR) by month 12, and major molecular response (MMR) by month 18 were achieved in 98, 63, and 59% of the patients, respectively. By month 36, 86% of the patients achieved CCyR and 74% achieved MMR. Thirty-eight patients (27%) experienced imatinib failure because of unsatisfactory response or intolerance (N = 9). In all, 28/148 patients (19%) underwent stem cell transplantation (SCT). In the SCT sub-cohort 2/23 patients diagnosed in CML-CP, 0/1 in CML-AP, and 2/4 in CML-BP, respectively, died of relapse (N = 3) or SCT-related complications (N = 2). This large pediatric trial extends and confirms data from smaller series that first-line imatinib in children is highly effective.
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Meinolf Suttorp received financial support as grants from Deutsche Forschungsgemeinschaft (DFG SU 122/3-1), Sonnenstrahl e.V. Dresden, Germany, Peter-Escher Foundation, Leipzig, Germany, and Mitteldeutsche Kinderkrebsforschung Foundation, Leipzig, Germany. The work of Ingmar Glauche and Philipp Schulze was supported by the German Federal Ministry of Research and Education, Grant number 031A315 “MessAge” and Grant number 031A424 “HaematoOpt”.
Conflict of interest
IG received research support (Institutional) and reimbursement for attending symposia from Bristol-Myers-Squibb. HHK received research support (Institutional) from Roche Pharma, and coverage of other expenses by Amgen, Astra Zeneca, Genomic Health, Lilly, and Roche Pharma. BS received fees for advisory board consultations (PARP inhibitors, not related to this trial) from Astra Zeneca. MSch received recent research support (Institutional) from Novartis in the time period from 2004 to 2012. MS received research support (Institutional) from Novartis and reimbursement for attending symposia organized by Bristol-Myers-Squibb, Novartis, and Pfizer. CT received research support (Institutional) from Bayer, Novartis, and Roche and is employed presently as CEO by AgenDix GmbH. The remaining authors declare that they have no conflict of interest. Neither Novartis nor any other pharmaceutical company was permitted prior insight to the results of trial CML-Paed II. Apart from the authors nobody participated in writing of the manuscript.
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Suttorp, M., Schulze, P., Glauche, I. et al. Front-line imatinib treatment in children and adolescents with chronic myeloid leukemia: results from a phase III trial. Leukemia 32, 1657–1669 (2018). https://doi.org/10.1038/s41375-018-0179-9
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