RESUMEN
PURPOSE: Familial aggregation among patients with several hematological malignancies has been revealed. This emphasizes the importance of genetic factors. Only few genes predisposing to familial hematological malignancies have been reported until now due to the low occurrence. We have described in previous study PRF1 and CEBPA variants that might contribute to the background of genetic factors, which encourage us to extend our investigations to other cooperating genes. The aim of this study is to determine whether germline additional sex combs-like 1 (ASXL1) gene mutations may be involved? METHODS/PATIENTS: In this study, we investigated the candidate gene ASXL1 by direct sequencing in 88 unrelated Tunisian and French families with aggregated hematological malignancies. RESULTS: We report a new p.Arg402Gln germline missense substitution in two related Tunisian patients which has not been previously described. We identified here this variant for the first time in non-Hodgkin lymphoma. The p.Arg402Gln variant was not found in 200 control chromosomes. In silico analysis has predicted potential deleterious effect on ASXL1 protein. CONCLUSIONS: From an extended candidate genes analyzed in the field of familial hematological malignancies, ASXL1 might be involved. This variant should be considered since a potential damaging effect was predicted by in silico analysis, with a view to develop functional assay in order to investigate the biological assessment.
Asunto(s)
Biomarcadores de Tumor/genética , Mutación de Línea Germinal/genética , Neoplasias Hematológicas/genética , Mutación Missense/genética , Proteínas Represoras/genética , Adulto , Secuencia de Aminoácidos , Análisis Mutacional de ADN , Femenino , Estudios de Seguimiento , Predisposición Genética a la Enfermedad , Neoplasias Hematológicas/diagnóstico , Humanos , Masculino , Estadificación de Neoplasias , Linaje , Pronóstico , Homología de Secuencia de AminoácidoRESUMEN
From January 1997 to December 2005, 337 patients with aggressive non Hodgkin's lymphoma were treated with one of the two successive multicentric non randomized protocols established in Tunisia. The mean age was 53 years. Most patients had diffuse large cell lymphoma with B phenotype in 86% and T in 14%. The performance status was 2 or 3 in 34% of cases. The LDH were elevated in 74% of cases. Advanced disease (III or IV stage) was noted in 59% of cases and 10% had a tumoral mass greater than 10 cm. According to the international prognostic index (IPI) adjusted to age, we distinguish four groups: group 1 (0 factor and age < 70 years), group 2 (1-3 factors and age < or = 60 years), group 3 (1-3 factors and age between 61 and 70 years) and group 4 (1-3 factors and age > 70 years). The patients of group 1 (N = 47) received 3 courses of CHOP regimen followed by irradiation. The patients of group 2 (N = 160) received 4 courses of ACVBP regimen (+ rituximab for 21 patients) followed by consolidation (N = 92) or peripheral blood progenitor cell transplantation (N = 20). The patients of group 3 (N = 61) received 8 courses of CHOP regimen (+ rituximab for 20 patients). The patients of group 4 (N = 69) received 6 courses of mini-CEOP regimen (N = 48) or 6 courses CVP regimen (N = 21). The 4-year overall survival was 56% and the 4-year event free survival was 49%.
Asunto(s)
Linfoma no Hodgkin/terapia , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales de Origen Murino , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Epirrubicina/administración & dosificación , Etopósido/administración & dosificación , Femenino , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Estado de Ejecución de Karnofsky , Linfoma de Células B Grandes Difuso/mortalidad , Linfoma de Células B Grandes Difuso/patología , Linfoma de Células B Grandes Difuso/terapia , Linfoma no Hodgkin/mortalidad , Linfoma no Hodgkin/patología , Masculino , Persona de Mediana Edad , Prednisolona/administración & dosificación , Prednisona/administración & dosificación , Estudios Prospectivos , Inducción de Remisión/métodos , Rituximab , Trasplante de Células Madre , Análisis de Supervivencia , Túnez , Vincristina/administración & dosificación , Adulto JovenRESUMEN
The aims of this flow cytometry study were to quantify B lymphoid precursors known as hématogones across age and clinical conditions and to study the immunophenotypic profile of these benign immature B cells. A total of 406 consecutive marrow specimens were analyzed for hématogones using 4-color flow cytometry during a 19 month period (60% males and 40% females). The age range was 3 months to 89 years. Hématogones were present in 80% of the specimens. Morphologic analysis of the smears from each patient showed small numbers of hématogones (<13% of total cellularity). The B cell population was defined by CD19 + CD45 bright positivity, coexpression of other B lineage markers: CD20, CD22, CD10, CD29, CD38 and CD58 in addition to HLA-DR and CD34. In our study we found a significant decline in hématogones with increasing age but a broad range was found at all ages. Marrow from some adults contained relatively high numbers. Diagnosis in these patients included cytopenias, infections, and neoplastic diseases. Distinction of hématogones is critical for disease management particularly after therapy of paediatric B acute lymphoblastic leukaemia to monitor for minimal residual disease.
Asunto(s)
Células Precursoras de Linfocitos B/citología , Células Precursoras de Linfocitos B/inmunología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Envejecimiento/inmunología , Envejecimiento/patología , Antígenos CD/metabolismo , Niño , Preescolar , Femenino , Citometría de Flujo , Humanos , Inmunofenotipificación , Lactante , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Adulto JovenRESUMEN
Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) is an aggressive form of acute leukemia that children ALL. Between 1991 and 1998, eight cases Ph+ ALL (7 males and one female) were diagnosed in our institution by successful cytogenetic studies. Median age was 37 years (range, 1-60 years). Leukocyte count was more than 50 x 109/l in 5 cases. According to the French-American-British (FAB) criteria, six patients were classified L1 and two L2. The Ph+ as sole anomaly was seen in 2 patients (25%), while additional chromosome changes were observed in 6 cases. Complete remission was achieved in 5 cases (62%) and relapse was observed in all cases? The 2-year survival rae was 25% confirming the worse prognosis of this leukemia when treated with standard chemotherapy.
Asunto(s)
Cromosoma Filadelfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Adolescente , Adulto , Niño , Preescolar , Citogenética , Femenino , Estudios de Seguimiento , Humanos , Lactante , Cariotipificación , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangre , Leucemia-Linfoma Linfoblástico de Células Precursoras/clasificación , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Pronóstico , Inducción de Remisión/métodos , Análisis de Supervivencia , Translocación GenéticaRESUMEN
Between 1989 and 1996, 21 cases with acute non lymphoblastic leukemia (11 males and 10 females) were diagnosed in our institution. Median age was 9 years (range, 2-15 years). Leukocyte count was more than 50,109/l in 47% of cases. According to the French-American-British (FAB) criteria, 7 cases were classified M1, 10 cases were classified M2, 1 classified M4Eo and 3 classified M5. All patients were treated with "7 + 3" protocol and complete remission was achieved in 17 cases (80%), 2 cases (10%) failed to respond and 2 (10%) died during induction. Relapse was observed in 15 cases. The 3-year survival rate was 20% and the relapse-free-survival rate was 12% confirming the worse prognosis of this leukemia when treated with standard chemotherapy.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia Monocítica Aguda/diagnóstico , Leucemia Monocítica Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mielomonocítica Aguda/diagnóstico , Leucemia Mielomonocítica Aguda/tratamiento farmacológico , Adolescente , Antibióticos Antineoplásicos/administración & dosificación , Antimetabolitos Antineoplásicos/administración & dosificación , Niño , Preescolar , Citarabina/administración & dosificación , Daunorrubicina/administración & dosificación , Femenino , Humanos , Leucemia Monocítica Aguda/sangre , Leucemia Monocítica Aguda/mortalidad , Leucemia Mieloide Aguda/sangre , Leucemia Mieloide Aguda/mortalidad , Leucemia Mielomonocítica Aguda/sangre , Leucemia Mielomonocítica Aguda/mortalidad , Masculino , Pronóstico , Inducción de Remisión , Estudios Retrospectivos , Análisis de SupervivenciaRESUMEN
Between 1989 and 1995, 42 cases with acute lymphoblastic leukemia (18 males and 24 females) were diagnosed in our institution. Median age was 38.5 years (range, 16-88 years). Leukocyte count was more than 30.10(9)/l in 54% of cases. According to the French-American-British (FAB) criteria, 67% were classified L1 and 33% L2. Sixteen patients were treated with 12LA80 protocol, 14 patients with LALA 85 protocol, 6 patients with LALA 87 protocol and 6 patients with EORTC protocol. Complete remission was achieved in 22 cases (52%), 8 cases (20%) failed to respond and 12 (28%) died during induction. Relapse was observed in 10 cases. The 4-year survival rate was 28% confirming the worse prognosis of this leukemia when treated with standard chemotherapy.
Asunto(s)
Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiología , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Progresión de la Enfermedad , Femenino , Humanos , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Pronóstico , Inducción de Remisión , Estudios Retrospectivos , Tasa de Supervivencia , Túnez/epidemiologíaRESUMEN
Sjögren's syndrome is characterized by an increased risk of developing non-Hodgkin's lymphoma. The lymphoma is most frequently extra-nodal, preferentially affecting the salivary gland: low-grade MALT lymphoma. Conversely, underlying Sjögren's syndrome has been recently identified by some authors in patients with non-Hodgkin's lymphoma. In the present report, we present three cases of Sjögren's syndrome disclosed by low-grade salivary gland MALT lymphoma. The patients were all women aged 33, 38 and 52 years. Extension work-up revealed nodal and bone marrow involvement in one case and no evidence of disseminated disease in the two others. Using the European criteria, all of our patients had certain Sjögren's syndrome. Labial salivary gland biopsy and immunopathological studies in newly diagnosed low-grade MALT lymphoma would be helpful in identifying the real frequency of this association.
Asunto(s)
Linfoma de Células B de la Zona Marginal/complicaciones , Neoplasias de las Glándulas Salivales/complicaciones , Síndrome de Sjögren/diagnóstico , Adulto , Femenino , Humanos , Persona de Mediana Edad , Síndrome de Sjögren/etiologíaRESUMEN
Between 1989 and 1996, 40 cases with acute leukemia (16 males and 24 females) were diagnosed in our institution. Median age was 65 years (range, 56-88 years). Leukocyte count was more than 30.109/l in 42% of cases. According to the French-American-British (FAB) criteria, 11 cases were classified lymphoblastic and 29 myeloblastic. Sixteen patients have received palliative treatment because of there age and there bad performance status. Only 24 patients have received curative treatment. Complete remission was achieved in 12 cases (50%), 5 cases (20%) failed to respond and 7 (30%) died during induction. Relapse was observed in 8 cases. The 2-year survival rate was 10% confirming the worse prognosis of the acute leukemia in elderly.
Asunto(s)
Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/epidemiología , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiología , Análisis Actuarial , Distribución por Edad , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Leucemia Mieloide Aguda/sangre , Leucemia Mieloide Aguda/tratamiento farmacológico , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangre , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Pronóstico , Inducción de Remisión , Estudios Retrospectivos , Distribución por Sexo , Análisis de Supervivencia , Resultado del Tratamiento , Túnez/epidemiologíaRESUMEN
The precision of immunological characterization of leukemias was improved by a certain number of technical innovations, particularly hybridoma production and standardization, resulting in monoclonal antibodies and definition of recognised cellular antigens (designated by CD: Cluster of Differentiation). The aim of this work was to determine the immunophenotyping profile of patients with leukemia, by means of a flow cytometric method: 66 blood samples coming from leukemic persons in the Sahel region were studied by flow cytometry, using about thirty monoclonal antibodies all marked with a fluorochrome, in one or two colour systems to assess their distribution according to type (lymphoid B or T / myeloid) and age, and to search for possible co-expressions of markers of different lineages. The marked preponderance of childhood B-ALL in our series is, at least partly, attributable to the age distribution of the Tunisian population. In agreement with studies from other countries, the majority of AML cases occurred among adults. A high proportion of AML cases in our series co-expressed markers of other lineages. Overall, accurate classification of acute leukemias was possible from a simple peripheral blood sample in 62 of 66 cases (93.9%).