RESUMO
OBJECTIVE: Fungal infections are a major cause of morbidity and mortality in the haematological patients. These infections are mainly due to Candida spp. and Aspergillus spp. Mortality by these infections is high, but rates have descended in the latest series due to better antifungal agents. Echinocan-dins are, in vitro, very active against Candida and Aspergillus spp. The objective of the study is to analyse the efï¬cacy and safety of micafungin in the antifungal prophylaxis of haema-tological patients on chemotherapy. METHODS: A multicentre, observational retrospective study was performed in 7 Haematology Depart-ments in Spain. Patients admitted to these departments with chemotherapy or immunosuppressive treatment, and who had received antifungal prophylaxis with micafungin between 1 January 2009 and 31 December 2014 were included. RESULTS: There were 5 cases of probable or proven fun-gal infection (4.8%) according to the 2008 EORTC criteria: 2 proven, 3 probable. The types of fungal infection were 3 as-pergillosis and 2 candidiasis. There were no drop-outs from the prophylaxis with micafungin due to toxicity. CONCLUSIONS: Micafungin is an antifungal agent which, used in prophylaxis, has demonstrated good efï¬cacy and an excellent toxicity proï¬le, making it an apparently interesting option in patients requiring antifungal prophylaxis during their hospitalisation episode.
Assuntos
Antifúngicos/uso terapêutico , Aspergilose/prevenção & controle , Candidíase/prevenção & controle , Doenças Hematológicas/complicações , Micafungina/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia Aplástica/complicações , Feminino , Humanos , Leucemia Mieloide Aguda/complicações , Linfoma/complicações , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Estudos Retrospectivos , Adulto JovemRESUMO
Acute myeloid leukemia (AML) is a heterogeneous disease whose prognosis is mainly related to the biological risk conferred by cytogenetics and molecular profiling. In elderly patients (⩾60 years) with normal karyotype AML miR-3151 have been identified as a prognostic factor. However, miR-3151 prognostic value has not been examined in younger AML patients. In the present work, we have studied miR-3151 alone and in combination with BAALC, its host gene, in a cohort of 181 younger intermediate-risk AML (IR-AML) patients. Patients with higher expression of miR-3151 had shorter overall survival (P=0.0025), shorter leukemia-free survival (P=0.026) and higher cumulative incidence of relapse (P=0.082). Moreover, in the multivariate analysis miR-3151 emerged as independent prognostic marker in both the overall series and within the unfavorable molecular prognostic category. Interestingly, the combined determination of both miR-3151 and BAALC improved this prognostic stratification, with patients with low levels of both parameters showing a better outcome compared with those patients harboring increased levels of one or both markers (P=0.003). In addition, we studied the microRNA expression profile associated with miR-3151 identifying a six-microRNA signature. In conclusion, the analysis of miR-3151 and BAALC expression may well contribute to an improved prognostic stratification of younger patients with IR-AML.
Assuntos
Biomarcadores Tumorais/genética , Leucemia Mieloide Aguda/genética , MicroRNAs/genética , Proteínas de Neoplasias/genética , Adolescente , Adulto , Idoso , Análise Citogenética , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Fatores de Risco , Transcriptoma , Adulto JovemRESUMO
Acute myeloid leukemia (AML) is a heterogeneous disease, and optimal treatment varies according to cytogenetic risk factors and molecular markers. Several studies have demonstrated the prognostic importance of microRNAs (miRNAs) in AML. Here we report a potential association between miRNA expression and clinical outcome in 238 intermediate-risk cytogenetic AML (IR-AML) patients from 16 institutions in the CETLAM cooperative group. We first profiled 670 miRNAs in a subset of 85 IR-AML patients from a single institution and identified 10 outcome-related miRNAs. We then validated these 10 miRNAs by individual assays in the total cohort and confirmed the prognostic impact of 4 miRNAs. High levels of miR-196b and miR-644 were independently associated with shorter overall survival, and low levels of miR-135a and miR-409-3p with a higher risk of relapse. Interestingly, miR-135a and miR-409-3p maintained their independent prognostic value within the unfavorable molecular subcategory (wild-type NPM1 and CEBPA and/or FLT3-ITD), and miR-644 retained its value within the favorable molecular subcategory. miR-409-3p, miR-135a, miR-196b and mir-644 arose as prognostic markers for IR-AML, both overall and within specific molecular subgroups.
Assuntos
Leucemia Mieloide Aguda/genética , MicroRNAs/análise , Adolescente , Adulto , Idoso , Feminino , Regulação Neoplásica da Expressão Gênica , Proteínas de Homeodomínio/genética , Humanos , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Nucleofosmina , Prognóstico , RiscoRESUMO
BACKGROUND AND OBJECTIVES: A consecutive series of acute myeloid leukemias (AML) patients was analyzed in conditions which reduce the inter-assay variations (the same flow cytometer, the same observers and the same panel of monoclonal antibodies) in order to investigate the prognostic information provided by flow cytometry. DESIGN AND METHODS: Two hundred and sixty-six bone marrow (BM) samples from 326 patients enrolled in the LMA-99 protocol from the CETLAM group were studied by multiparametric flow cytometry. Immunophenotyping studies were performed on erythrocyte-lysed BM samples. Antigen expression of leukemic cells was analyzed using triple stainings with fluorochrome-conjugated combinations of monoclonal antibodies. RESULTS: CD2 was positive in 21 cases (8%); an associated inv(16) was detected in eight CD2+ cases (38%). Two-year overall survival (OS) rate for CD2+/inv(16)+ patients was 75%, whereas it was 0% for CD2+/inv(16)- patients and 47% for CD2- patients (p=0.0001). CD36 was expressed in 37% of patients (n=98). Two-year leukemia-free survival (LFS) rate was 34% for CD36+ patients and 55% for CD36- patients (p=0.001). In the multivariate analysis, CD2+ (RR=8.4; p=0.0001) and adverse karyotype (RR=10.2; p=0.0001) were associated with a lower CR rate, CD36+ (RR=1.5; p=0.03), CD2+ (RR=2; p=0.04) and adverse karyotype (RR=4; p=0.0001) were associated with a lower OS and CD36+ (RR=2; p=0.002) and adverse karyotype (RR=3.5; p=0.005) predicted a lower LFS. CONCLUSIONS: CD2+ patients had a very poor OS when CD2/inv(16)+ cases were excluded. CD36 and CD2 expression at diagnosis can provide prognostically important information in adult de novo AML.
Assuntos
Antígenos CD2/metabolismo , Antígenos CD36/metabolismo , Leucemia Mieloide/metabolismo , Doença Aguda , Adolescente , Adulto , Anticorpos Monoclonais , Medula Óssea/metabolismo , Medula Óssea/patologia , Aberrações Cromossômicas , Inversão Cromossômica , Feminino , Citometria de Fluxo , Humanos , Imunofenotipagem , Cariotipagem , Leucemia Mieloide/genética , Leucemia Mieloide/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de SobrevidaRESUMO
We describe two cases of acute myelocytic leukemia (AML), classified as M4 and M1 in the French-American-British classification, with unbalanced translocations der(16)t(11;16)(q23;p13) and der(18)t(11;18) (q22;p11.2), respectively. Molecular studies using Southern blot and reverse transcriptase-polymerase chain reaction showed an MLL rearrangement due to an internal duplication of the gene in both cases. Fluorescence in situ hybridization disclosed the presence of an extra copy of the MLL gene on 16p13 and 18p11.2, respectively, as a result of the partial trisomy of chromosome 11q. Our two cases clearly show that tandem duplication of the MLL gene may occur in AML with a partial 11q trisomy. Thus, systematic screening of this molecular defect should be performed in patients with unbalanced translocations involving 11q22 approximately q23-->qter.
Assuntos
Cromossomos Humanos , Proteínas de Ligação a DNA/genética , Duplicação Gênica , Leucemia Mieloide Aguda/genética , Proto-Oncogenes , Fatores de Transcrição , Translocação Genética , Adulto , Southern Blotting , Análise Citogenética , Feminino , Histona-Lisina N-Metiltransferase , Humanos , Hibridização in Situ Fluorescente , Leucemia Mieloide Aguda/etiologia , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Proteína de Leucina Linfoide-Mieloide , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
The MLL gene, located at 11q23 band, is frequently disrupted by different chromosomal rearrangements that occur in a variety of hematological malignancies. MLL rearrangements are associated with distinct clinical features and a poor prognosis. The aim of this study was to analyze the incidence and the prognostic significance of MLL rearrangements in a consecutive series of adult AML patients and to determine the immunophenotypic features of these cases. The identification of abnormal immunophenotypes could be used for the detection of minimal residual disease (MRD). Ninety-three adult patients with de novo acute myeloid leukemia (AML) were analyzed by Southern blot in order to detect MLL rearrangements (MLL+). RT-PCR and genomic long-range PCR were performed to further characterize MLL partial tandem duplication (PTD) in those patients in whom conventional karyotype did not show 11q23 chromosomal translocations. All the patients were homogeneously immunophenotyped at diagnosis. MLL rearrangements were detected in 13 (14%) patients. Four patients (5%) showed 11q23 translocations by karyotypic conventional analysis. Nine patients (10%) revealed PTD of MLL and one patient showed a MLL cleavage pattern. The MLL+ patients usually expressed myeloid and monocytic antigens CD33 (12/13 cases), CD13 (9/13), CD117 (9/13), CD64 (11/13) and in some cases CD14 (4/11). HLA-DR was also positive in (12/13). Eight out of 13 cases expressed the stem cell marker CD34. Only one patient revealed lymphoid marker reactivity (CD7) and CD56 was expressed in 5/13 cases. All the MLL+ patients showed at least one aberrant phenotype at diagnosis, which allowed us to set out a simple panel for the MRD studies. Twenty-seven samples from eight patients in morphologic complete remission (CR) were analyzed using the aberrant immunologic combinations detected at diagnosis. Phenotypically abnormal cells were detected in all the patients who subsequently relapsed, whereas only one patient with MRD+ remained in CR. Owing to the high level of residual leukemic cells, the MLL+ patients showed a short CR duration and a poor survival. In conclusion, immunophenotyping may be a suitable approach to investigating MRD status in AML patients with PTD of the MLL gene.
Assuntos
Proteínas de Ligação a DNA/genética , Rearranjo Gênico , Leucemia Mieloide/genética , Neoplasia Residual/genética , Proto-Oncogenes , Fatores de Transcrição , Translocação Genética , Doença Aguda , Adolescente , Adulto , Anticorpos Monoclonais/imunologia , Anticorpos Antineoplásicos/imunologia , Antígenos CD/imunologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Southern Blotting , Cromossomos Humanos Par 11/genética , Proteínas de Ligação a DNA/metabolismo , Intervalo Livre de Doença , Citometria de Fluxo , Duplicação Gênica , Histona-Lisina N-Metiltransferase , Humanos , Imunofenotipagem , Cariotipagem , Leucemia Mieloide/tratamento farmacológico , Leucemia Mieloide/patologia , Pessoa de Meia-Idade , Proteína de Leucina Linfoide-Mieloide , Neoplasia Residual/tratamento farmacológico , Neoplasia Residual/patologia , Reação em Cadeia da Polimerase , Prognóstico , Indução de RemissãoAssuntos
Fatores Imunológicos/uso terapêutico , Interferon-alfa/uso terapêutico , Mastocitose/complicações , Mielofibrose Primária/etiologia , Medula Óssea/patologia , Hemorragia Cerebral/etiologia , Terapia Combinada , Evolução Fatal , Feminino , Antagonistas dos Receptores Histamínicos/uso terapêutico , Humanos , Interferon alfa-2 , Cetotifeno/uso terapêutico , Mastocitose/tratamento farmacológico , Mastocitose/patologia , Mastocitose/cirurgia , Mastocitose/terapia , Pessoa de Meia-Idade , Prednisona/uso terapêutico , Mielofibrose Primária/patologia , Prognóstico , Proteínas Recombinantes , EsplenectomiaRESUMO
A patient with thalassemia minor (TM) is reported who ingested 80 g of alcohol/day and presented an important overload of iron with deposits and a hepatic iron ratio compatible with primary hemochromatosis. The results obtained from the study of histocompatibility antigens, clinical manifestations and family analysis discarded the possibility of two genetic diseases, beta-thalassemia and primary hemochromatosis, being concomitantly present in the same progeny. Thalassemia minor and alcoholic hepatopathy are considered as having acted together and being responsible for the iron overload. The relation between alcohol ingested, TM and iron deposits is discussed.