Assuntos
Neoplasias do Sistema Nervoso Central , Infiltração Leucêmica , Sarcoma Mieloide , Neoplasias da Medula Espinal , Medula Espinal/patologia , Feminino , Humanos , Leucemia Promielocítica Aguda/patologia , Leucemia Promielocítica Aguda/terapia , Infiltração Leucêmica/patologia , Infiltração Leucêmica/terapia , Pessoa de Meia-Idade , Indução de Remissão , Sarcoma Mieloide/patologia , Sarcoma Mieloide/terapia , Neoplasias da Medula Espinal/patologia , Neoplasias da Medula Espinal/terapiaRESUMO
The benefit of azacitidine treatment in survival of high-risk myelodysplastic syndromes (MDS) patients compared with conventional care treatment (CCT) has not been established outside clinical trials. To assess its effectiveness, we compared overall survival (OS) between azacitidine and conventional treatment (CCT) in high-risk MDS patients, excluding those undergoing stem cell transplantation, submitted to the Spanish MDS registry from 2000 to 2013. Several Cox regression and competing risk models, considering azacitidine as a time-dependent covariate, were used to assess survival and acute myeloblastic leukemia (AML) progression. Among 821 patients included, 251 received azacitidine. Median survival was 13.4 (11.8-16) months for azacitidine-treated patients and 12.2 (11-14.1) for patients under CCT (P=0.41). In a multivariate model, age, International prognostic scoring system and lactate dehydrogenase were predictors of OS whereas azacitidine was not (adjusted odds ratio 1.08, 95% confidence interval 0.86-1.35, P=0.49). However, in patients with chromosome 7 abnormalities, a trend toward a better survival was observed in azacitidine-treated patients (median survival 13.3 (11-18) months) compared with CCT (median survival 8.6 (5-10.4) months, P=0.08). In conclusion, our data show that, in spite of a widespread use of azacitidine, there is a lack of improvement in survival over the years. Identification of predicting factors of response and survival is mandatory.
Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Azacitidina/uso terapêutico , Síndromes Mielodisplásicas/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Progressão da Doença , Feminino , Seguimentos , Humanos , Incidência , Leucemia Mieloide Aguda/epidemiologia , Leucemia Mieloide Aguda/etiologia , Masculino , Síndromes Mielodisplásicas/mortalidade , Síndromes Mielodisplásicas/patologia , Prognóstico , Sistema de Registros , Espanha/epidemiologia , Resultado do TratamentoRESUMO
Cytogenetic analysis is useful in the diagnosis and to assess prognosis of B-cell chronic lymphocytic leukemia (B-CLL). However, successful cytogenetics by standard techniques has been hindered by the low in vitro mitotic activity of the malignant B-cell population. Fluorescence in situ hybridization (FISH) has become a useful tool, but it does not provide an overall view of the aberrations. To overcome this hurdle, two DNA-based techniques have been tested in the present study: comparative genomic hybridization (CGH) and amplotyping by arbitrarily primed PCR (AP-PCR). Comparative genomic hybridization resolution depends upon the 400-bands of the human standard karyotype. AP-PCR allows detection of allelic losses and gains in tumor cells by PCR fingerprinting, thus its resolution is at the molecular level. Both techniques were performed in 23 patients with stage A B-CLL at diagnosis. The results were compared with FISH. The sensitivity of AP-PCR was greater than CGH (62% vs. 43%). The use of CGH combined with AP-PCR allowed to detect genetic abnormalities in 79% (15/19) of patients in whom G-banding was not informative, providing a global view of the aberrations in a sole experiment. This study shows that combining these two methods with FISH, makes possible a more precise genetic characterization of patients with B-CLL.
Assuntos
Amplificação de Genes , Leucemia Linfocítica Crônica de Células B/genética , Reação em Cadeia da Polimerase/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Aberrações Cromossômicas , Impressões Digitais de DNA , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hibridização de Ácido Nucleico , Sensibilidade e EspecificidadeAssuntos
Cromossomos Humanos Par 11/genética , Cromossomos Humanos Par 2/genética , Amplificação de Genes , Leucemia Mieloide Aguda/genética , Idoso , Idoso de 80 Anos ou mais , Evolução Biológica , Proteínas de Ligação a DNA/genética , Histona-Lisina N-Metiltransferase , Humanos , Hibridização in Situ Fluorescente , Masculino , Proteína de Leucina Linfoide-Mieloide , Proteínas Tirosina Quinases/genética , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas c-bcr , Proto-Oncogenes/genética , Receptores de Glutamato/genética , Fatores de Transcrição/genéticaAssuntos
Artrite Juvenil/complicações , Doenças do Sistema Imunitário/etiologia , Anti-Inflamatórios/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Juvenil/tratamento farmacológico , Artrite Juvenil/patologia , Pré-Escolar , Humanos , Doenças do Sistema Imunitário/tratamento farmacológico , Doenças do Sistema Imunitário/patologia , Ativação de Macrófagos/imunologia , Masculino , Metotrexato/uso terapêutico , Metilprednisolona/uso terapêutico , Síndrome , Resultado do TratamentoRESUMO
Cytogenetic analysis of unstimulated short-term bone marrow cell cultures was performed on 280 patients with multiple myeloma and related disorders. In 65% of the cases, an additional short term B-cell stimulated culture was also examined. Chromosomally abnormal clones were found in 31% of the patients, 15% in Waldenström macroglobulinemia. 25% in monoclonal gammopathies, 33% in multiple myeloma, and 50% in plasma cell leukemia. Three primary chromosomal breakpoints were recurrently involved: 14q32, 16q22, and 22q11. Structural rearrangements of chromosome 1 were the most frequent (26% of the abnormal cases), but always as a secondary change. Rearrangements of band 14q32 were found in 22% of the abnormal cases. Among the multiple myeloma patients who showed an abnormal karyotype, 33 (46%) were hyperdiploid, most frequently, with 52-56 chromosomes, 29 patients (40%) were pseudodiploid, and the remaining 12 cases (14%) were hypodiploid. A highly significant relation was observed between the presence of an abnormal karyotype and the following clinical parameters: stage III (P = 0.0001), bone marrow plasma cell infiltration greater than 30% (P = 0.0001), presence of bone lesions (P = 0.0009), and beta 2-microglobulin levels greater than 4 mg/L (P = 0.0001).
Assuntos
Aberrações Cromossômicas , Transtornos Cromossômicos , Mieloma Múltiplo/genética , Fragilidade Cromossômica , Humanos , Cariotipagem , Leucemia Plasmocitária/genética , Células Tumorais Cultivadas , Macroglobulinemia de Waldenstrom/genéticaRESUMO
Our aim was to evaluate the clinical use of cytogenetic analysis as a prognostic factor in the outcome of newly diagnosed multiple myeloma (MM) patients. The present series includes 111 newly diagnosed MM patients treated with one of three standard-dose regimens or autologous transplantation over an 8-year time interval. As expected, the presence of an abnormal karyotype (39% of patients) correlated with poor prognosis (progression rate 63% v 47%, P = 0.042), shorter event-free (EFS, P = 0.014) and overall (OS, P = 0.005) survival. Two distinct cytogenetic abnormalities were the most significant variables that influenced EFS and OS in the univariate analysis. The presence of hypodiploid karyotypes or rearrangements of band 22q11 were associated with higher progression rate (P = 0.001) and shorter EFS (P < 0.024) and OS (P < 0.004). The median EFS and OS for patients with hypodiploidy was 4 and 7 months respectively. Multivariate analysis showed that absence of hypodiploidy was the most favourable prognostic variable for OS (P = 0.022) followed by stage < or = IIA, serum calcium < or = 2875 micromol/l, and absence of abnormalities 22q. The data suggest that the presence of hypodiploid karyotypes and rearrangements on 22q11 band show a higher progression rate and shorter survival in MM patients.