Your browser doesn't support javascript.
loading
Imatinib treatment and longitudinal growth in pediatric patients with chronic myeloid leukemia: influence of demographic, pharmacological, and genetic factors in the German CML-PAED cohort.
Stiehler, Sophie; Sembill, Stephanie; Schleicher, Oliver; Marx, Michaela; Rauh, Manfred; Krumbholz, Manuela; Karow, Axel; Suttorp, Meinolf; Woelfle, Joachim; Maj, Carlo; Metzler, Markus.
Afiliação
  • Stiehler S; Pediatric Oncology and Hematology, Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen, Friedrich-Alexander-Universität, Erlangen-Nürnberg.
  • Sembill S; Pediatric Oncology and Hematology, Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen, Friedrich-Alexander-Universität, Erlangen-Nürnberg, Germany; Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), Erlangen. stephanie.sembill@uk-erlangen.de.
  • Schleicher O; Pediatric Oncology and Hematology, Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen, Friedrich-Alexander-Universität, Erlangen-Nürnberg, Germany; Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander-Universität, Erlangen-Nürnberg.
  • Marx M; Pediatric Endocrinology, Department of Pediatrics and Adolescent Medicine, University Children's Hospital, Friedrich-Alexander-Universität, Erlangen-Nürnberg.
  • Rauh M; Pediatric Oncology and Hematology, Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen, Friedrich-Alexander-Universität, Erlangen-Nürnberg.
  • Krumbholz M; Pediatric Oncology and Hematology, Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen, Friedrich-Alexander-Universität, Erlangen-Nürnberg, Germany; Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), Erlangen.
  • Karow A; Pediatric Oncology and Hematology, Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen, Friedrich-Alexander-Universität, Erlangen-Nürnberg, Germany; Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), Erlangen.
  • Suttorp M; Pediatric Hemato-Oncology, Medical Faculty, Technical University Dresden, Dresden.
  • Woelfle J; Pediatric Endocrinology, Department of Pediatrics and Adolescent Medicine, University Children's Hospital, Friedrich-Alexander-Universität, Erlangen-Nürnberg.
  • Maj C; Centre for Human Genetics, University of Marburg, Marburg.
  • Metzler M; Pediatric Oncology and Hematology, Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen, Friedrich-Alexander-Universität, Erlangen-Nürnberg, Germany; Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), Erlangen.
Haematologica ; 109(8): 2555-2563, 2024 Aug 01.
Article em En | MEDLINE | ID: mdl-38497150
ABSTRACT
In children and adolescents, impaired growth due to tyrosine kinase inhibitor therapy remains an insufficiently studied adverse effect. This study examines demographic, pharmacological, and genetic factors associated with impaired longitudinal growth in a uniform pediatric cohort treated with imatinib. We analyzed 94 pediatric patients with chronic myeloid leukemia (CML) diagnosed in the chronic phase and treated with imatinib for >12 months who participated in the Germany-wide CML-PAEDII study between February 2006 and February 2021 (clinicaltrials gov. Identifier NCT00445822). During imatinib treatment, significant height reduction occurred, with medians of -0.35 standard deviation score (SDS) at 12 months and -0.76 SDS at 24 months. Cumulative height SDS change (Δ height SDS) showed a more pronounced effect in prepubertal patients during the first year but were similar between prepubertal and pubertal subgroups by the second year (-0.55 vs. -0.50). From months 12 to 18 on imatinib, only 18% patients achieved individually longitudinal growth adequate to the growth standard (Δ height SDS ≥0). When patients were divided into two subgroups based on median Δ height SDS (classifier Δ height SDS > or ≤-0.37) after 1 year on imatinib therapy, cohort 1 (Δ height SDS ≤-0.37) showed younger age at diagnosis, a higher proportion of prepubertal children, but also better treatment response and higher imatinib serum levels. Exploring the association of growth parameters with pharmacokinetically relevant single nucleotide polymorphisms, known for affecting imatinib response, showed no correlation. This retrospective study provides new insights into imatinib-related growth impairment. We emphasize the importance of optimizing treatment strategies for pediatric patients to realize their maximum growth potential.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Leucemia Mielogênica Crônica BCR-ABL Positiva / Mesilato de Imatinib Limite: Adolescent / Child / Child, preschool / Female / Humans / Infant / Male País/Região como assunto: Europa Idioma: En Revista: Haematologica Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Leucemia Mielogênica Crônica BCR-ABL Positiva / Mesilato de Imatinib Limite: Adolescent / Child / Child, preschool / Female / Humans / Infant / Male País/Região como assunto: Europa Idioma: En Revista: Haematologica Ano de publicação: 2024 Tipo de documento: Article