RESUMO
Disease relapse is the greatest cause of treatment failure in paediatric B-cell acute lymphoblastic leukaemia (B-ALL). Current risk stratifications fail to capture all patients at risk of relapse. Herein, we used a machine-learning approach to identify B-ALL blast-secreted factors that are associated with poor survival outcomes. Using this approach, we identified a two-gene expression signature (CKLF and IL1B) that allowed identification of high-risk patients at diagnosis. This two-gene expression signature enhances the predictive value of current at diagnosis or end-of-induction risk stratification suggesting the model can be applied continuously to help guide implementation of risk-adapted therapies.
Assuntos
Quimiocinas/genética , Interleucina-1beta/genética , Proteínas com Domínio MARVEL/genética , Aprendizado de Máquina/estatística & dados numéricos , Leucemia-Linfoma Linfoblástico de Células Precursoras B/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Doença Aguda , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras B/mortalidade , Valor Preditivo dos Testes , Recidiva , Medição de Risco/normas , Análise de Sobrevida , Transcriptoma/genética , Falha de TratamentoRESUMO
BACKGROUND: Increase in intraocular pressure is a recognized complication of corticosteroid treatment via intravitreal or periocular injections for treatment of a range of conditions including macular oedema and retinal neovascularization. DESIGN: This surveillance study was designed to determine the incidence and nature of severe intraocular pressure elevation as a complication of intravitreal or periocular corticosteroid injections in Australia and New Zealand. PARTICIPANTS: Seventeen cases meeting the defined criteria of severe intraocular pressure elevation, above 35 mmHg, following an intravitreal or periocular corticosteroid injection were included in the study. METHODS: Over an 18-month period, ophthalmologists were invited to report cases to the Australian and New Zealand Ophthalmic Surveillance Unit. After reporting, further demographic and clinical information was sought via a follow-up questionnaire. MAIN OUTCOME MEASURES: Intraocular pressure elevation above 35 mmHg. RESULTS: Follow-up questionnaires were received for 20 cases of 34 initially reported to the unit. Seventeen met the defined criteria. Triamcinolone acetonide was used in all 17 cases, with 16 delivered as a 4-mg intravitreal injection. There was an absence of identified underlying risk factors in the majority of cases with personal history of glaucoma in 2 of 17 cases. No cases reported a positive family history of glaucoma. Trabeculectomy was performed in 8 of 17 patients (47%) for intraocular pressure management. CONCLUSIONS: Severe intraocular pressure elevation following intravitreal or periocular corticosteroid injection can occur in the absence of risk factors such as personal and family history of glaucoma. The severe intraocular pressure elevation may ultimately require trabeculectomy.