RESUMEN
The aim of this nationwide study was to describe the epidemiology and profile of bacterial infections (BI), invasive fungal disease (IFD) and viral infections (VI) in patients with de novo and relapsed/refractory (rel/ref) acute myeloid leukemia (AML). Within the studied group of 250 children with primary AML, at least one infectious complication (IC) was diagnosed in 76.0% (n = 190) children including 85.1% (n = 504) episodes of BI, 8.3% (n = 49) - IFD and 6.6% (n = 39) - VI. Among 61 patients with rel/ref AML, at least one IC was found in 67.2% (n = 41) of children including 78.8% (n = 78) of BI, 14.1% (n = 14) of IFD and 7.1% (n = 7) of VI. In all AML patients, within BI Gram-negative strains were predominant. Half of these strains were multi-drug resistant. Characteristics of IFD and VI were comparable for de novo and rel/ref AML. The infection-related mortality was significantly higher, while survival from infection was significantly lower in patients with rel/ref disease.
Asunto(s)
Infecciones/etiología , Infecciones/mortalidad , Leucemia Mieloide Aguda/complicaciones , Leucemia Mieloide Aguda/mortalidad , Adolescente , Niño , Preescolar , Manejo de la Enfermedad , Susceptibilidad a Enfermedades , Farmacorresistencia Microbiana , Resistencia a Antineoplásicos , Femenino , Humanos , Incidencia , Lactante , Infecciones/diagnóstico , Infecciones/tratamiento farmacológico , Leucemia Mieloide Aguda/patología , Leucemia Mieloide Aguda/terapia , Masculino , Mortalidad , RecurrenciaRESUMEN
The germline variant at rs3824662 in GATA3 is a risk locus for Philadelphia-like acute lymphoblastic leukemia (Ph-like ALL), the biological subtype of B-cell precursor (BCP)-ALL defined by a distinct gene expression profile and the presence of specific somatic aberrations including rearrangements of CRLF2. In this study, we investigated whether rs3824662 in GATA3 associates with CRLF2 expression in leukemic cells and predicts prognosis in pediatric BCP-ALL patients treated according to the ALL Intercontinental Berlin-Frankfurt-Münster (IC BFM) 2009 (n = 645) and the ALL IC BFM 2002 (n = 216) protocols. High expression of CRLF2 was observed at both protein and mRNA levels (fourfold higher in AA than in CA + CC) among GATA3 AA variant carriers, independent of the presence of P2RY8-CRLF2 fusion. Additionally, the AA variant at rs3824662 was a significant factor affecting minimal residual disease level at the end of induction phase and overall survival regardless of the risk group and the protocol. The germline variant at rs3824662 in GATA3 is a prognostic factor which associates with CRLF2 expression in leukemic cells supporting the hypothesis that GATA3 may have a regulatory effect on the CRLF2 pathway in pediatric BCP-ALL.
Asunto(s)
Factor de Transcripción GATA3/genética , Polimorfismo de Nucleótido Simple , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Receptores de Citocinas/genética , Células Cultivadas , Niño , Preescolar , Femenino , Mutación de Línea Germinal , Humanos , Masculino , Fusión de Oncogenes , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patología , Receptores de Citocinas/metabolismo , Receptores Purinérgicos P2Y/genética , Análisis de SupervivenciaRESUMEN
The objective of this nation-wide study was to evaluate the epidemiology and profile of bacterial (BI), viral (VI), and invasive fungal disease (IFD) in patients treated for non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL) between the years 2013-2015. In the analyzed period of time, within the studied group of 328 children diagnosed and treated for lymphomas, at least one infectious complication (IC) was diagnosed i.e. 39.3% children. In these patients there were 350 episodes of IC, therein 80.6% episodes of BI, 11.1% episodes of VI, and 8.3% episodes of IFD. In both groups, NHL and HL patients, a stable level of bacterial infections, with an increase in resistance rates, and increased levels of viral and fungal infections were observed. Profile of BI does not depend on lymphoma type, with predominance of Gram-negative bacteria and higher prevalence of MDR pathogens. The overall survival of lymphoma patients with IC was comparable for different types of infections.
Asunto(s)
Infecciones Bacterianas/epidemiología , Enfermedad de Hodgkin/terapia , Infecciones Fúngicas Invasoras/epidemiología , Linfoma no Hodgkin/terapia , Virosis/epidemiología , Adolescente , Profilaxis Antibiótica/métodos , Infecciones Bacterianas/microbiología , Infecciones Bacterianas/prevención & control , Niño , Preescolar , Farmacorresistencia Bacteriana Múltiple , Femenino , Enfermedad de Hodgkin/inmunología , Enfermedad de Hodgkin/mortalidad , Humanos , Incidencia , Lactante , Infecciones Fúngicas Invasoras/microbiología , Infecciones Fúngicas Invasoras/prevención & control , Estimación de Kaplan-Meier , Linfoma no Hodgkin/inmunología , Linfoma no Hodgkin/mortalidad , Masculino , Polonia/epidemiología , Prevalencia , Factores de Riesgo , Virosis/prevención & control , Virosis/virologíaAsunto(s)
Proteínas de Ciclo Celular/genética , Neoplasias del Sistema Nervioso Central/etiología , Mutación de Línea Germinal , Heterocigoto , Recurrencia Local de Neoplasia/etiología , Proteínas Nucleares/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Adolescente , Neoplasias del Sistema Nervioso Central/patología , Niño , Preescolar , Femenino , Estudios de Seguimiento , Efecto Fundador , Humanos , Lactante , Masculino , Recurrencia Local de Neoplasia/patología , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patología , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Tasa de SupervivenciaRESUMEN
The inactivation of tumor suppressor genes located within 9p21 locus (CDKN2A, CDKN2B) occurs in up to 30% of children with B-cell precursor acute lymphoblastic leukemia (BCP-ALL), but its independent prognostic significance remains controversial. In order to investigate the prognostic impact of deletions and promoter methylation within 9p21, 641 children with newly diagnosed BCP-ALL using methylation specific multiplex ligation-dependent probe amplification (MS-MLPA) were investigated. A total of 169 (26.4%) microdeletions in 9p21 were detected, of which 71 were homozygous. Patients with CDKN2A homozygous deletions were older at diagnosis (p < .001), more frequently steroid resistant (p = .049), had higher WBC count (p < .001), higher MRD at Day 15 (p = .013) and lower relapse-free survival [p = .028, hazard ratio: 2.28 (95% confidence interval: 1.09-4.76)] than patients without these alterations. CDKN2A homozygous deletions coexisted with IKZF1 and PAX5 deletions (p < .001). In conclusion, CDKN2A homozygous deletions, but not promoter methylation, are associated with poor response to treatment and increased relapse risk of pediatric BCP-ALL.
