Management of chronic myeloid leukemia in children and adolescents: tyrosine kinase inhibitor efficacy, survivorship challenges, and long-term hemostatic safety
Notice bibliographique
Résumé
Background. The introduction of BCR::ABL1 tyrosine kinase inhibitors (TKIs) has transformed pediatric chronic myeloid leukemia (CML) from a life-threatening disease often requiring transplantation into a manageable chronic condition. However, this success necessitates a shift in clinical focus from acute survival to the multi-system, long-term toxicities incurred over a lifetime of therapy. Objective. The systematic scoping review synthesizes evidence from 2021 to the present, evaluating the comparative efficacy of TKI generations, long-term developmental and reproductive safety, and the complex cardiovascular and hemostatic risks in children and adolescents with CML. Methods. Following PRISMA-ScR guidelines, a systematic search of PubMed, Scopus, and Web of Science was conducted for studies published from January 2021. Key guidelines from the last decade were included. Observational studies were appraised using the Newcastle-Ottawa Quality Assessment Scale (NOQAS). Data were extracted and synthesized narratively across six key domains: 1) epidemiology, 2) comparative efficacy, 3) growth and endocrine safety, 4) fertility and reproductive safety, 5) cardiovascular and hemostatic safety, and 6) emergent therapies. Results. Pediatric CML presents with more aggressive features (e. g., higher leukocytosis, larger splenomegaly) than adult CML. While second-generation (2G) TKIs (dasatinib, nilotinib) demonstrate superior rates of deep and rapid molecular response (DMR) compared to imatinib, this has not translated into a proven overall survival (OS) benefit. However, achieving DMR is a prerequisite for treatment-free remission (TFR), a critical goal in pediatrics to mitigate long-term toxicities. Safety analysis revealed significant, TKI class-effect toxicities, including high rates of short stature (up to 26.5% in pre-pubertal patients) and low bone mineral density (35.2%). Growth impairment is comparable across imatinib and 2G-TKIs. A critical, sex-specific risk exists for fertility, with TKI teratogenicity confirmed in maternal exposure (5% anomaly rate) but not in paternal exposure, where large registry data show no increased risk. A critical analysis of “cardiovascular risk” reveals a divergent hemostatic risk spectrum: Nilotinib and ponatinib confer a pro-thrombotic (arterial, venous) risk, whereas dasatinib induces an anti-platelet (hemorrhagic) risk via SRC-kinase inhibition. Surveys confirm these specific risks are poorly recognized, with no standardized surveillance in pediatric practice. Conclusions. TKI selection in pediatric CML must evolve beyond efficacy alone to a multi-disciplinary, risk-stratified model. This includes balancing the TFR-enabling efficacy of 2G-TKIs against their specific toxicity profiles. This review proposes a “Hemostatic Risk Spectrum” as an essential framework, mandating that TKI selection be guided by the patient’s baseline hemostatic risk (e. g., avoiding nilotinib in thrombophilia, avoiding dasatinib in bleeding disorders). Standardized protocols for monitoring endocrine, metabolic, and hemostatic health are urgently required to ensure safe, long-term survivorship.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,001 |
| Méta-épidémiologie (sens large) | 0,002 | 0,000 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,001 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».