RESUMEN
Early recognition of children with chronic phase chronic myeloid leukaemia (CML-CP) at risk for developing a lymphoid blast crisis (LyBC) is desirable, because therapy options in CML-LyBC are limited. We used Multiplex Ligation-dependent Probe Amplification to determine whether B-cell lymphoid leukaemia-specific copy number alterations (CNAs) (e.g. IKZF1, PAX5, CDKN2A deletions) could be detected in CML-CP and may be used to predict disease progression to LyBC. CNAs were detected in all patients with CML-LyBC, but in none of the 77 patients with CML-CP. Based on this study we conclude that CNAs remain a hallmark of disease progression.
Asunto(s)
Biomarcadores de Tumor/genética , Variaciones en el Número de Copia de ADN/genética , ADN de Neoplasias/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Crisis Blástica/genética , Niño , Progresión de la Enfermedad , Diagnóstico Precoz , Humanos , Factor de Transcripción Ikaros/genética , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa Multiplex/métodos , Proteínas de Neoplasias/genética , Mutación Puntual , PronósticoRESUMEN
Outcome for relapsed paediatric acute myeloid leukaemia (AML) remains poor. Strong prognostic factors at first relapse are lacking, which hampers optimization of therapy. We assessed the frequency of molecular aberrations (FLT3, NRAS, KRAS, KIT, WT1 and NPM1 genes) at first relapse in a large set (n = 198) of relapsed non-French-American-British M3, non-Down syndrome AML patients that received similar relapse treatment. We correlated molecular aberrations with clinical and biological factors and studied their prognostic relevance. Hotspot mutations in the analysed genes were detected in 92 out of 198 patients (46·5%). In 72 of these 92 patients (78%), molecular aberrations were mutually exclusive for the currently analysed genes. FLT3-internal tandem repeat (ITD) (18% of total group) mutations were most frequent, followed by NRAS (10·2%), KRAS (8%), WT1 (8%), KIT (8%), NPM1 (5%) and FLT3-tyrosine kinase domain (3%) mutations. Presence of a WT1 aberration was an independent risk factor for second relapse (Hazard Ratio [HR] = 2·74, P = 0·013). In patients who achieved second complete remission (70·2%), WT1 and FLT3-ITD aberrations were independent risk factors for poor overall survival (HR = 2·32, P = 0·038 and HR = 1·89, P = 0·045 respectively). These data show that molecular aberrations at first relapse are of prognostic relevance and potentially useful for risk group stratification of paediatric relapsed AML and for identification of patients eligible for personalized treatment.
Asunto(s)
Genes Relacionados con las Neoplasias/genética , Leucemia Mieloide Aguda/genética , Mutación/genética , Proteínas de Neoplasias/genética , Adolescente , Niño , Preescolar , Supervivencia sin Enfermedad , Femenino , Humanos , Lactante , Cariotipo , Leucemia Mieloide Aguda/terapia , Masculino , Nucleofosmina , Recurrencia , Factores de RiesgoRESUMEN
Chemotherapy-induced neutropenia is a major dose-limiting side effect of intensive chemotherapy in cancer patients. Recently, pegfilgrastim (a product with a long half-life, resulting in once-per-cycle dosage) was introduced to prevent neutropenia in adults. The authors report 32 episodes of pegfilgrastim use in seven pediatric cancer patients to diminish chemotherapy-induced neutropenia. Feasibility was assessed by adherence to treatment protocol and safety was assessed by adverse effects. There were only two treatment delays (6%) due to neutropenia. No short-term adverse effects were recorded. The use of pegfilgrastim is feasible in pediatric cancer patients, without short-term adverse effects or major treatment delay due to neutropenia.