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Article

Discontinuation of Imatinib in Children with Chronic Myeloid Leukemia: A Study from the International Registry of Childhood CML

1
Inserm CIC 1402, University Hospital of Poitiers, 86000 Poitiers, France
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Medical Faculty, Pediatric Hemato-Oncology, Technical University Dresden, 01307 Dresden, Germany
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Department of Pediatric Hematology, Trousseau Hospital, 75012 Paris, France
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Department of Pediatric Hematology, Robert Debré University Hospital, 75019 Paris, France
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Department of Pediatric Hematology, University Hospital of Nantes, 44000 Nantes, France
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Department of Pediatric Hematology, University Hospital of Besançon, 25056 Besançon, France
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Department of Pediatric Hematology, University Hospital of Lille, 59000 Lille, France
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Department of Pediatric Hematology, University Hospital of Nice, 06000 Nice, France
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Department of Pediatric Hematology, University Hospital of Toulouse, 31000 Toulouse, France
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Department of Hematology, University Medical Center Utrecht, 3584 Utrecht, The Netherlands
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Department of Pediatrics, Rigshospitalet, 2100 Copenhagen, Denmark
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Belarusian Research Centre for Pediatric Oncology, Hematology and Immunology, 223053 Minsk, Belarus
*
Author to whom correspondence should be addressed.
Academic Editor: Masahiro Kizaki
Cancers 2021, 13(16), 4102; https://doi.org/10.3390/cancers13164102
Received: 5 July 2021 / Revised: 6 August 2021 / Accepted: 10 August 2021 / Published: 15 August 2021
(This article belongs to the Special Issue Molecular Genetics and Treatment of Chronic Myeloid Leukemia)
About 50% of adults with chronic myeloid leukemia (CML) in sustained deep molecular response (DMR) to tyrosine kinase inhibitors (TKI) could discontinue the treatment permanently without molecular relapse. Recommendations regarding discontinuation apply only for adults because childhood CML is a very rare disease and represents a separate entity. The aim of our retrospective study was to assess within the International Registry of Childhood CML, the rate of children remaining in molecular response after discontinuation of imatinib in a context of DMR defined as BCR-ABL1/ABL1 < 0.01% (MR4) for at least two years. Eighteen patients less than 18 years old at diagnosis of CML exhibiting a sustained DMR followed by imatinib discontinuation were identified. After discontinuation, the molecular free remission rate was 61%, 56% and 56% at 6, 12 and 36 months, respectively. Our findings represent the basis of recommendation regarding discontinuation for physicians involved in the pediatric CML field.
Within the International Registry of Childhood Chronic Myeloid Leukemia (CML), we identified 18 patients less than 18 years old at diagnosis of CML who were in the chronic phase and exhibiting a sustained deep molecular response (DMR) to imatinib defined as BCR-ABL1/ABL1 < 0.01% (MR4) for at least two years followed by discontinuation of imatinib. Before discontinuation, the median duration of imatinib was 73.2 months (range, 32–109) and the median duration of MR4 was 46.2 months (range, 23.9–98.6). Seven patients experienced loss of major molecular response (MMR) 4.1 months (range, 1.9–6.4) after stopping and so restarted imatinib. The median molecular follow-up after discontinuation was 51 months (range, 6–100) for the nine patients without molecular relapse. The molecular free remission rate was 61% (95% CI, 38–83%), 56% (95% CI, 33–79%) and 56% (95% CI, 33–79%) at 6, 12 and 36 months, respectively. Six of the seven children who experienced molecular relapse after discontinuation regained DMR (median, 4.7 months; range, 2.5–18) after restarting imatinib. No withdrawal syndrome was observed. In univariate analysis, age, sex, Sokal and ELTS scores, imatinib treatment and DMR durations before discontinuation had no influence on treatment free remission. These data suggest that imatinib can be safely discontinued in children with sustained MR4 for at least two years. View Full-Text
Keywords: chronic myeloid leukemia; imatinib; children chronic myeloid leukemia; imatinib; children
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MDPI and ACS Style

Millot, F.; Suttorp, M.; Ragot, S.; Leverger, G.; Dalle, J.-H.; Thomas, C.; Cheikh, N.; Nelken, B.; Poirée, M.; Plat, G.; Versluys, B.; Lausen, B.; Borisevich, M. Discontinuation of Imatinib in Children with Chronic Myeloid Leukemia: A Study from the International Registry of Childhood CML. Cancers 2021, 13, 4102. https://doi.org/10.3390/cancers13164102

AMA Style

Millot F, Suttorp M, Ragot S, Leverger G, Dalle J-H, Thomas C, Cheikh N, Nelken B, Poirée M, Plat G, Versluys B, Lausen B, Borisevich M. Discontinuation of Imatinib in Children with Chronic Myeloid Leukemia: A Study from the International Registry of Childhood CML. Cancers. 2021; 13(16):4102. https://doi.org/10.3390/cancers13164102

Chicago/Turabian Style

Millot, Frédéric, Meinolf Suttorp, Stéphanie Ragot, Guy Leverger, Jean-Hugues Dalle, Caroline Thomas, Nathalie Cheikh, Brigitte Nelken, Marilyne Poirée, Geneviève Plat, Birgitta Versluys, Birgitte Lausen, and Marina Borisevich. 2021. "Discontinuation of Imatinib in Children with Chronic Myeloid Leukemia: A Study from the International Registry of Childhood CML" Cancers 13, no. 16: 4102. https://doi.org/10.3390/cancers13164102

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