RESUMEN
The study aim was to analyze incidence and presentation features of chronic lymphocytic leukemia (CLL) in Chile, in Amerindian population and in non-Native. Between 2012 and 2019, 912 patients were diagnosed, and 13 (1.4%) were Amerindian. The estimated incidence in Chilean population was 1.17/100,000 person per year, while in Amerindian, 0.09/100,000 person per year. Median age was 73 years. At diagnosis, 48, 27, and 25%, had low (0), intermediate (I/II) and high-risk (III/IV) disease on Rai classification. Diagnostic immunophenotypic Matutes score was ≥4 in 90%. Median follow-up was 37 months (range 2-87). 5-year OS was 56%, with median overall survival (OS) not reached. It was worse in men, ≥65 years, high-risk and those with increased prolymphocytes (CLL/PL). This study shows low incidence and worse OS in Chilean CLL patients, compared to those from European countries, despite similar clinical features. It also demonstrates that CLL is very uncommon in Amerindian population.
Asunto(s)
Leucemia Linfocítica Crónica de Células B , Anciano , Chile/epidemiología , Humanos , Inmunofenotipificación , Incidencia , Leucemia Linfocítica Crónica de Células B/diagnóstico , Leucemia Linfocítica Crónica de Células B/epidemiología , Recuento de Linfocitos , MasculinoRESUMEN
Splenic diffuse red pulp small B-cell lymphoma (SDRPL) is considered an indolent neoplasm and its pathogenesis is not well known. We investigated the molecular characteristics of 19 SDRPL patients, 5 of them with progressive disease. IGHV genes were mutated in 9/13 (69%). Cytogenetic and molecular studies identified complex karyotypes in 2 cases, and IGH rearrangements in 3, with PAX5 and potentially TCL1 as partners in each one of them. Copy number arrays showed aberrations in 69% of the tumors, including recurrent losses of 10q23, 14q31-q32, and 17p13 in 3, and 9p21 in 2 cases. Deletion of 7q31.3-q32.3 was present in only 1 case and no trisomies 3 or 18 were detected. NOTCH1 and MAP2K1 were mutated in 2 cases each, whereas BRAF, TP53, and SF3B1 were mutated each in single cases. No mutations were found in NOTCH2 or MYD88. Four of the 5 patients with aggressive disease had mutations in NOTCH1 (2 cases), TP53 (1 case), and MAP2K1 (1 case). The progression-free survival of patients with mutated genes was significantly shorter than in the unmutated (P=0.011). These findings show that SDRPL share some mutated genes but not chromosomal alterations, with other splenic lymphomas, that may confer a more aggressive behavior.
Asunto(s)
Biomarcadores de Tumor/genética , Linfoma de Células B/genética , MAP Quinasa Quinasa 1/genética , Mutación , Receptor Notch1/genética , Neoplasias del Bazo/genética , Proteína p53 Supresora de Tumor/genética , Adulto , Anciano , Biomarcadores de Tumor/análisis , Biopsia , Chile , Variaciones en el Número de Copia de ADN , Análisis Mutacional de ADN , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Europa (Continente) , Femenino , Eliminación de Gen , Dosificación de Gen , Reordenamiento Génico , Genes de las Cadenas Pesadas de las Inmunoglobulinas , Predisposición Genética a la Enfermedad , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Estimación de Kaplan-Meier , Linfoma de Células B/química , Linfoma de Células B/patología , Linfoma de Células B/terapia , Masculino , Persona de Mediana Edad , Técnicas de Diagnóstico Molecular , Fenotipo , Valor Predictivo de las Pruebas , Factores de Riesgo , Neoplasias del Bazo/química , Neoplasias del Bazo/patología , Neoplasias del Bazo/terapia , Factores de TiempoRESUMEN
BACKGROUND: Chronic lymphoproliferative disorders include a variety of diseases which are often a diagnostic problem for clinical hematologists. AIM: To study prospectively the distribution and incidence of chronic lymphoproliferative disorders in Chile and compare them with those of other Western, Latin American and Oriental countries. PATIENTS AND METHODS: A group of 132 patients were studied in a 36 months period (1999-2001), with a panel of monoclonal antibodies. A score for chronic lymphocytic leukemia was employed to differentiate it from other B-cell disorders. RESULTS: The median age was 63 years old (range 32-94). Most patients had B-cell tumors (109) and the rest (23), T-cell tumors (82% vs 18%). Forty five percent of patients with B-cell tumors had a chronic lymphocytic leukemia (CLL), while the others were disseminated lymphomas. The incidence of T-cell tumors was slightly higher than that of other Western countries. Noteworthy is that the most common of these disorders was adult T cell leukemia/lymphoma (ATLL), in concordance with the high HTLV-1 seroprevalence in Chile. CONCLUSIONS: A morphologic, immunophenotypic and pathological study in a large number of patients with chronic lymphoproliferative disorders in Chile, shows a relatively low incidence of CLL when compared to other chronic B-cell tumors and a high representation of ATLL associated to HTLV-1 infection, compared with other Western countries. The lower incidence of CLL in our study might be due to patient's selection and/or underdiagnosis of this disease as a substantial proportion of CLL are asymptomatic.
Asunto(s)
Trastornos Linfoproliferativos/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Chile/epidemiología , Enfermedad Crónica , Femenino , Virus Linfotrópico T Tipo 1 Humano/inmunología , Humanos , Incidencia , Leucemia Linfoide/epidemiología , Leucemia Linfoide/inmunología , Linfoma/epidemiología , Linfoma/inmunología , Trastornos Linfoproliferativos/inmunología , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
We estimated by quantitative flow cytometry (FC) the expression of CD13, CD33, CD34 and CD117 antigens in cells from 64 patients with acute myeloid leukaemia (AML) and 22 normal bone marrows (BMs). The method converts fluorescence intensity into number of antigen molecules per cell, measured by antibody binding capacity (ABC). The number of molecules per cell in normal BM was 9.5+/-5.7 for CD13, 7+/-2.3 for CD33, 6+/-0.7 for CD34, and 6.3+/-1.5x10(3) for CD117. AML blasts expressed 11.4+/-12.4 molecules per cell for CD13, 9.5+/-9.7 for CD33, 74+/-2328.5 for CD34 and 12.5+/-33 x 10(3) for CD117. The number of CD34 and CD117 molecules were significantly higher in AML than in normals (P<0.0001 and P<0.05, respectively) while only in a few cases, CD13 and CD33 were abnormally expressed in myeloblasts. Our results indicate that quantitative analysis of CD34 and CD117 may be useful to detect minimal residual disease (MRD) and could be tested in a future to monitor therapy in AML.
Asunto(s)
Antígenos CD34/biosíntesis , Biomarcadores de Tumor/biosíntesis , Leucemia Mieloide/genética , Proteínas de Neoplasias/análisis , Células Madre Neoplásicas/química , Proteínas Proto-Oncogénicas c-kit/biosíntesis , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antígenos CD34/genética , Biomarcadores de Tumor/genética , Niño , Preescolar , Femenino , Regulación Leucémica de la Expresión Génica , Humanos , Leucemia Mieloide/diagnóstico , Leucemia Mieloide/patología , Masculino , Persona de Mediana Edad , Proteínas de Neoplasias/biosíntesis , Proteínas de Neoplasias/genética , Neoplasia Residual , Proteínas Proto-Oncogénicas c-kit/genéticaRESUMEN
Background: Adult T cell leukemia lymphoma is a lymphoproliferative syndrome etiologically associated to human T cell lymphotropic virus type I. Aim: To describe the clinical and laboratory features of 26 caucasian chilean patients, with HTLV-I positive adult T-cell leukemia lymphoma (ATLL). Material and methods: Diagnostic criteria included clinical features, cell morphology, immunophenotype, HTLV-I serology and/or DNA analysis by southern blot or PCR. Results: According to the clinical presentation, 12 cases had the acute ATLL form, 6 had a lymphoma, 4 the chronic form and 4 had smoldering ATLL. The median presentation age was 50 years, younger than the Japanese patients, but significantly older than patients from other south american countries (eg Brasil, Jamaica, Colombia). The main clinical features: lymphadenopathy, skin lesions and hepatosplenomegaly, were similar in frequency to those of patients from other countries, except for the high incidence of associated neurological disease. Tropical spastic paraparesis (TSP) in our series of ATLL, was seen in one third of the patients (8/26). A T-cell immunophenotype was shown in all 26 cases and HTLV-I serology was positive in 25/26 patients. Molecular analysis on the seronegative patient showed clonal integration of proviral HTLV-I DNA into the lymphocytes DNA, and thus he may have been a poor responder to the retroviral infection. Proviral DNA integration was also demonstrated in 15/16 patients being clonal in 10, polyclonal in 3 (all smoldering cases) and oligoclonal in one. Conclusions: ATLL in Chile has similar clinical and laboratory features than the disease in other parts of the world, except for a younger age than japanese patients but older than those from other latin american countries and a high incidence of patients with associated TSP. Detailed morphological and immunophenotypic analysis of the abnormal circulating lymphocytes, together with the documentation of HTLV-I by serology and/or DNA analysis are key tests for the identification of this disease
Asunto(s)
Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anticuerpos Anti-HTLV-I/aislamiento & purificación , Leucemia-Linfoma de Células T del Adulto/inmunología , Ensayo de Inmunoadsorción Enzimática , Anticuerpos Anti-HTLV-I , Leucemia-Linfoma de Células T del Adulto/diagnóstico , Reacción en Cadena de la Polimerasa , Supervivencia sin Enfermedad , Inmunofenotipificación , Biomarcadores/sangreRESUMEN
Patients and methods: Eight patients, our of 368, with acute myeloid leukemia that were studied in the Hematology Laboratory of a public hospital in Santiago, were classified as LMA-MO. Results: Blast cell morphology was undifferentiated or of subtype FAB-L2 lymphoblastic leukemia with medium sized blasts, agranular basophilic cytoplasm, reticular nuclear chromatin and a prominent nucleolus. Cytochemical staining was negative for peroxidase and esterases, immunophenotyping showed the expression of one or more myeloid antigens (CD13, CD33) and was negative for lymphoid antigens. Immunocytochemical expression of myeloperoxidase was positive in the three cases where it was performed. Only one patient achieved complete remission and is free of disease after 36 months of follow up. All other patients died without obtaining remission, six shortly after the onser and one 12 months after. Conclusions: The diagnosis of LMA-MO is essential considering its dismal prognosis
Asunto(s)
Humanos , Masculino , Femenino , Recién Nacido , Lactante , Persona de Mediana Edad , Leucemia Mieloide/diagnóstico , Leucemia Mieloide/clasificación , Peroxidasa/aislamiento & purificación , Esterasas/aislamiento & purificación , /aislamiento & purificación , Histocitoquímica/métodos , Inmunofenotipificación/métodosRESUMEN
We describe the clinical and pathological features of 23 Afro-Caribbean patients with adult T-cell leukaemia/lymphoma admitted to the Queen Elizabeth Hospital, Barbados over a 5 year period. There were 9 males and 14 females, with a median age of 38 years (range 14-84). Twelve had acute leukaemia, 10 lymphoma (including 4 with solitary extra nodal lesions) and 1 smouldering subtype. Two patients had a past history of tropical spastic paraparesis/HTLV I associated myelopathy (TSP/HAM). The prognosis was poor, with only 3 complete responses to chemotherapy (CHOP) lasting from 9 to 36 months. We conclude that ATLL in Barbados is similar to the disease in other Caribbean islands and Japan, except that in Barbados the age of onset is over a decade younger than in Japan.(AU)
Asunto(s)
Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Leucemia-Linfoma de Células T del Adulto/patología , Leucemia-Linfoma de Células T del Adulto/inmunología , Leucemia-Linfoma de Células T del Adulto/transmisión , Barbados , Pronóstico , Estudios ProspectivosRESUMEN
We describe two siblings who developed adult T-cell leukaemia lymphoma (ATLL) within 4 years. Both were black of Afro-Caribbean extraction, but one had been born in the United Kingdom and had visited the Caribbean only once. Both patients were HTLV-1 seropositive, as was their mother; their father and brother were negative. The older siblings had the lymphoma form of ATLL, whilst the younger had chronic ATLL. The former was unresponsive to chemotherapy and died of progressive disease; the latter chemotherapy and died of progressive disease; the latter experienced transient responses to various treatments and is alive 5 years after presentation. Immunophenotyping showed a CD4+, CD25+ phenotype; Southern blot demonstrated a monoclonal integration of HTLV-I in the tissues involved. This report, of the first familial ATLL in the U.K., supports the suggestion of transmission of HTLV-I from mother to child and documents and the development of ATLL in second-generation Caribbean immigrants (AU)
Asunto(s)
Informes de Casos , Humanos , Masculino , Femenino , Leucemia-Linfoma de Células T del Adulto/transmisión , Transmisión Vertical de Enfermedad Infecciosa , Antígenos CD4/sangre , Negro o Afroamericano , Salud de la Familia , Leucemia-Linfoma de Células T del Adulto/etnología , Leucemia-Linfoma de Células T del Adulto/patología , Ganglios Linfáticos/patología , Linaje , Receptores de Interleucina-2/análisis , Trinidad y Tobago/etnologíaRESUMEN
Six healthy relatives of 3 adult T-cell leukemia lymphoma (ATLL) patients and 6 members of a Caribbean family immigrant to the UK have been investigated for the presence of HTLV-I and expression of interleukin 2(IL-2) receptors. Serum antibodies to HTLV-I were detected in all but 4 samples. Four to 10 percent of circulating cells from 3/4 seropositive donors studied displayed IL-2 receptors (anti-Tac+) and were shown to be convoluted lymphocytes by light microscopy morphology and immunoelectromicroscopy. After 5 to 28 days in culture, cells from 4 seropositive donors reacted with monoclonal antibodies (MAbs) against the HTLV-I core proteins, p19 and p24, and released retrovirus particles. Simmilar experiments with blood from 3 seronegative donors from the same families and 4 normal controls proved negative. Our findings indicate that seropositive individuals harbour the virus in a population of T-lymphocytes which may then acquire receptors for IL-2. These individuals are at risk of developing ATLL. (AU)