RESUMEN
Nearly 50% of patients with de novo acute myeloid leukemia (AML) harbor an apparently normal karyotype (NK) by conventional cytogenetic techniques showing a very heterogeneous prognosis. This could be related to the presence of cryptic cytogenetic abnormalities (CCA) not detectable by conventional methods. The study of copy number alterations (CNA) and loss of heterozygozity (LOH) in hematological malignancies is possible using a high resolution SNP-array. Recently, in clinical practice the karyotype study has been complemented with the identification of point mutations in an increasing number of genes. We analyzed 252 de novo NK-AML patients from Hospital La Fe (n = 44) and from previously reported cohorts (n = 208) to identify CCA by SNP-array, and to integrate the analysis of CCA with molecular alterations detected by Next-Generation-sequencing. CCA were detected in 58% of patients. In addition, 49% of them harbored CNA or LOH and point mutations, simultaneously. Patients were grouped in 3 sets by their abnormalities: patients carrying several CCA simultaneously, patients with mutations in FLT3, NPM1 and/or DNMT3A and patients with an amalgam of mutations. We found a negative correlation between the number of CCA and the outcome of the patients. This study outlines that CCA are present in up to 50% of NK-AML patients and have a negative impact on the outcome. CCA may contribute to the heterogeneous prognosis.
Asunto(s)
Aberraciones Cromosómicas , Leucemia Mieloide Aguda/genética , Polimorfismo de Nucleótido Simple , Adulto , Anciano , Anciano de 80 o más Años , Variaciones en el Número de Copia de ADN , Femenino , Estudios de Seguimiento , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Cariotipo , Leucemia Mieloide Aguda/mortalidad , Pérdida de Heterocigocidad , Masculino , Persona de Mediana Edad , Nucleofosmina , Pronóstico , Estudios Prospectivos , Adulto JovenRESUMEN
INTRODUCTION: Inv(3)(q21.3q26.2)/t(3;3)(q21.3;q26.2) is a rare poor prognosis cytogenetic abnormality present in acute myeloid leukemia (AML) and other myeloid neoplasms. OBJECTIVE: The aim of this study was to evaluate the outcome of a cohort of 61 patients with newly diagnosed AML with inv(3)/t(3;3) treated with homogeneous intensive chemotherapy protocols conducted by the Spanish PETHEMA and CETLAM cooperative groups between 1999 and 2017. METHODS: In this retrospective study the main clinical and biologic parameters were collected. The complete response (CR) rate, the cumulative incidence of relapse (CIR) and the overall survival (OS) were calculated. An analysis of prognostic factors for survival was performed. RESULTS: Sixty-one patients received induction and only 18 (29%) achieved CR (median age, 46 years). Allogeneic hematopoietic stem cell transplantation (alloHSCT) was performed in 36 patients (59%), 15 with active disease. One- and 4-year CIR were 52% and 56%. One- and 4-year OS probabilities were 41% and 13%. By multivariate analysis monosomal karyotype (MK) was associated with poorer OS (HR 2.0, P = .017). CONCLUSION: Inv(3)/t(3;3) AML is a poor prognosis entity with low response to standard chemotherapy and to alloHSCT because of frequent and early relapse. MK was associated with a poorer prognosis. Improved therapeutic strategies are clearly needed.
Asunto(s)
Inversión Cromosómica , Cromosomas Humanos Par 3 , Leucemia Mieloide Aguda/genética , Translocación Genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Terapia Combinada , Femenino , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Cariotipificación , Leucemia Mieloide Aguda/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Inducción de Remisión , Estudios Retrospectivos , Análisis de Supervivencia , Trasplante Homólogo , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Invasive candidiasis is a severe infection among onco-hematological patients, with an attributable mortality around 40%. Micafungin has shown efficacy in antifungal prophylaxis among hematopoietic stem cell transplant recipients and in the treatment of esophageal candidiasis. AIMS: To assess the role of micafungin in the treatment of invasive candidiasis among onco-hematological patients. METHODS: Literature review. RESULTS: In a study on 126 patients with candidemia treated with micafungin, an overall response rate of 83% was reported. A double-blind study of 531 patients with invasive candidiasis comparing micafungin (100mg/day) versus liposomal amphotericin B (3mg/kg/day) reported success in 90% of patients in both arms, with a more favorable safety profile with micafungin. Other double blind randomized, phase III study compared two doses of micafungin (100mg/day and 150mg/day) with standard doses of caspofungin (70mg loading dose, then 50mg/day) in adults with invasive candidiasis. Overall success rate was 74% for micafungin 100mg/day, 70% for micafungin 150mg/day, and 71% for caspofungin. A double blind randomized study compared micafungin (2mg/kg/day) to liposomal amphotericin B (3mg/kg/day) in the treatment of invasive candidiasis in children with a predominance of infections with non-albicans Candida spp. Overall success rate was similar (73% for micafungin and 76% for liposomal amphotericin B). CONCLUSIONS: Comparative phase III studies have demonstrated non-inferiority of micafungin compared to standard antifungal agents for invasive candidiasis. Micafungin is safe and effective in the treatment of children and adults with invasive candidiasis. Effectivity in invasive infections caused by non-albicans Candida spp is especially relevant in onco-hematological patients receiving fluconazole prophylaxis.