Serum level of intercellular adhesion molecule-1 in children with malignant lymphoma

Toestimate the serum levels of soluble intercellular adhesion molecule-1 [s-ICAM-1] in children newly diagnosed with lymphoma and to correlate levels of s-ICAM-1 in lymphoma patients with clinical stage, pathological types, clinical and laboratory data and patient outcome. Thirty-five children with newly-diagnosed malignant lymphoma [Non-Hodgkin's lymphoma, NHL: 23], Hodgkin's disease [HD: 12], and 8 apparently healthy subjects of matched age and sex taken as a control group were studied. For the patients and control group, the following tests were performed: complete blood count, and the following biochemical investigations: liver function tests, lactate dehydrogenase [LDH], and soluble ICAM-1 estimation using ELISA. In addition, for patients, pathological examination of lymph node biopsy for pathological grading, bone marrow aspiration and biopsy were done. Patients were observed for over 12 months or until death. Serum ICAM-1 increased more in HD and NHL than in the control group [p < 0.000]; also s-ICAM-1 increased in advanced stages and high-grade NHL [p < 0.008, 0.04, respectively]. LDH levels were higher in patients compared to controls [p < 0.000]. There was a positive correlation between high levels of s-ICAM-1 and increased levels of LDH in HD [r = 0.72, p < 0.008] and a positive correlation between high levels of s-ICAM-1 and increased ALT in NHL patients. A positive correlation between s-ICAM-1 levels and the presence of B symptoms in HD and NHL, and a positive correlation between elevated s-ICAM-1 levels and worse outcome in HD and NHL were detected. The data indicate that in children with malignant lymphoma, high serum levels of ICAM-1 correlated with tumor aggressiveness, and quantification of s-ICAM-1 levels may identify a subgroup of children with worse prognosis. Therefore, detection of s-ICAM-1 levels in children with malignant lymphoma might represent an additional disease-associated marker for use in the clinical management of the patients

Detection of free circulating Epstein-Barr virus DNA in plasma of patients with HodgkinÆs disease / Detecção do DNA livre circulante do vírus Epstein-Barr no plasma de pacientes com doença de Hodgkin

CONTEXT AND OBJECTIVE: Free circulating Epstein-Barr virus (EBV) DNA is often present in the plasma of HodgkinÆs disease patients. The aim here was to evaluate the prevalence of this finding, its correlation with the immunohistochemical expression of LMP-1 (latent membrane protein 1) and the influence of other clinical factors. DESIGN AND SETTING: Prospective study in two public tertiary institutions: Hematology Service, Universidade Federal do Rio de Janeiro, and Oncology Service, Instituto Nacional do Câncer, Rio de Janeiro. METHODS: A cohort of 30 patients with newly diagnosed HodgkinÆs disease was studied. The control group consisted of 13 healthy adult volunteers. EBV DNA was determined by conventional polymerase chain reaction (PCR). RESULTS: The median age was 28 years, and 16 patients were women. Advanced disease was present in 19 patients, and six were HIV-positive. EBV DNA was present in the plasma of 13 patients and one control (43 percent versus 8 percent, p = 0.03). EBV DNA prevalence was higher in HIV-positive patients (100 percent versus 29 percent, p = 0.0007) and those with advanced disease (63 percent versus 9 percent, p = 0.006). Among HIV-negative patients alone, EBV DNA prevalence remained higher in those with advanced disease. EBV DNA was found in 10/11 patients with LMP-1 expression in the lymph nodes, and in 3/19 without LMP-1 expression (kappa coefficient = 0.72). CONCLUSION: EBV DNA was present in 91 percent of patients with EBV-associated HodgkinÆs disease, and in all patients with HIV-associated HodgkinÆs disease. EBV DNA prevalence was higher in patients with advanced disease, irrespective of HIV status.

CONTEXTO E OBJETIVO: O DNA do vírus Epstein-Barr (EBV) está freqüentemente presente no sangue periférico de pacientes com doença de Hodgkin. O objetivo deste estudo foi avaliar a prevalência deste achado, e correlacioná-lo com a expressão imunoistoquímica da LMP-1 (latent membrane protein 1) e a presença de outros fatores clínicos. TIPO DE ESTUDO E LOCAL: Estudo prospectivo realizado no Serviço de Hematologia da Universidade Federal do Rio de Janeiro e no Serviço de Oncologia do Instituto Nacional do Câncer, Rio de Janeiro, Brasil. MÉTODOS: Trinta pacientes com doença de Hodgkin recém-diagnosticada foram estudados, assim como um grupo controle composto por 13 indivíduos saudáveis. O DNA do EBV no plasma foi determinado pela reação em cadeia da polimerase (PCR) convencional. RESULTADOS: A idade mediana foi 28 anos e 16 pacientes eram do sexo feminino. A doença disseminada esteve presente em 19 pacientes e seis eram HIV+. O DNA do EBV foi detectado no plasma de 13 pacientes e um controle (43 por cento versus 8 por cento, p = 0,03). A prevalência do DNA do EBV foi maior nos pacientes HIV+ (100 por cento versus 29 por cento, p = 0,0007) e naqueles com doença disseminada (63 por cento versus 9 por cento, p = 0,006). Quando somente os pacientes HIV-negativos foram analisados, a prevalência do DNA do EBV permaneceu maior nos pacientes com doença disseminada. A prevalência do DNA do EBV variou de acordo com o subtipo histológico: foi de 32 por cento nos pacientes com esclerose nodular e de 100 por cento nos pacientes com celularidade mista e depleção linfocítica (p = 0,02). O DNA do EBV foi encontrado em 10/11 pacientes com a expressão da LMP-1 em linfonodos, e em 3/19 pacientes sem a expressão da LMP-1 (coeficiente de kappa = 0,72). CONCLUSÕES: O DNA circulante do EBV foi detectado no plasma de 91 por cento dos pacientes com doença de Hodgkin associada ao EBV, e em todos os pacientes com doença de Hodgkin associada ao HIV. A prevalência do DNA circulante do EBV foi detectado no plasma de 91% dos pacientes com doença de Hodgkin associada ao EBV, e em todos os pacientes com doença de Hodgkin associada ao HIV. A prevalência do DNA circulante do EBV foi maior nos pacientes com doença avançada, independentemente do status para o HIV.

Detecção de potenciais marcadores moleculares séricos da doença de Hodgkin / Detection of potential serum molecular markers for Hodgkin's disease

MOTIVAÇAO: Neste trabalho foi analisado o perfil de proteínas séricas de pacientes com doença de Hodgkin (DH) localizada e avançada em busca de novos e potenciais biomarcadores para o diagnóstico médico. MATERIAIS E MÉTODOS: O perfil de proteínas presentes no soro de 14 indivíduos saudáveis, 14 pacientes com DH avançada e 15 pacientes com DH localizada, assim como pools de soro dos respectivos grupos, foi analisado em gel desnaturante de poliacrilamida a 12 por cento corado pela prata. A densitometria e a intensidade média das bandas de interesse foram estudadas utilizando-se o Kodak 1D Scientific Imaging System. RESULTADOS E CONCLUSÕES: O perfil protéico apresentou acentuada variação entre os pacientes examinados; entretanto foi observada a indução predominante de determinadas proteínas (aproximadamente 26kDa e 18kDa), cuja expressão foi substancialmente diferente quando em comparação com os controles (p < 0,01). Estas proteínas podem potencialmente constituir-se em marcadores moleculares de acompanhamento da evolução e do tratamento da doença.

Serum lactate dehydrogenase level in hodgkin's disease relationhip to certain features at the time of diagnosis

lactate dehydrogenase [LDH] has been suggested as a non-specific marker in many tumors including Hodgkin's disease [HD]. The aim of this study is to verify the relationship of serum LDH level to certain features at the time of diagnosis of HD. This study was conducted at the Medical City-Baghdad during the period of October 2000 till April 2002. The study included 54 patients with HD and 55 healthy control subjects. For all patients routine investigations and other specific investigations for staging purposes were done when possible. Serum LDH level was estimated in all patients and control subjects. High serum LDH levels were significantly related to advanced stages of disease [III and IV], presence of mediaslinal and/or hilar tumors, splenomegaly, and liver and bone marrow involvement, but not significantly related to histological types, B-symptoms, bulky disease, intraabdominal lymphadenopathy and disease relapse. The serum LDH concentration, at the time of diagnosis of HD, is significantly related to several features, many of them are well known poor prognostic features in HD

Serum levels of soluble Fas [S-FAS] and soluble intercellular adhesion molecule-1 [S-ICAM-1] in childhood solid tumors: correlation with clinical features and outcome

The levels of s-Fas and s-ICAM-1 conjointly in sera of patients with malignant diseases were evaluated in sera of sixty-two children with solid tumor on admission. They included thirty-four children with non- Hodgkin's lymphoma [NHL], three with Hodgkin's lymphoma [HL], eight with neuroblastoma, four with retinoblastoma, five with osteosarcoma, three with Ewing's sarcoma and five with Wilm's tumor. For comparative purposes, serum samples were obtained from ten healthy children who were comparable in age and sex with the patients. The study revealed significant increase of s-Fas as well as sICAM-1 in children with solid malignant tumors as a whole and irrespective of the pathological type compared with controls. The sensitivities were 100% and 93.5%, respectively. The levels of either s-Fas or sICAM-1 reflected organomegaly and outcome in children with solid tumor as a whole. Moreover, they reflected tumor spread, grade and burden in cases with NHL. Significant positive correlation existed between s-Fas and sICAM-1

Autoimmune haemolytic anaemia, immune thrombocytopenia, and leucopenia - an unusual presentation of hodgkin's disease

We report an unusual case of modular sclerosing Hodgkin's disease in a 17 year old women presenting with intermittent fever, progressive weight loss and enlarged cervical and anxillary lymp nodes. Laboratory test revealed severe Coombs' positive haemolytic anaemia, and progressive thrombocytopenia and leucopenia, associated with erythroid, myeloid and megakaryocytic hyperplasia, but with no evidence of lymphomatous infiltration in the bone marrow. Transfusion of compatible blood became possible only after prednisone therapy and a single intravenous dose of vincristine. Appropriate chemotherapy led to normalization of the peripheral blood counts and a negative direct Coombs' test.

Soluble interleukin-2 receptor [sIL-2R] as a tumor marker in hematologic malignancies

This work aimed to evaluate serum levels of sIL-2R in some of the hematologic malignancies and to find out if it could be a predictive marker of tumor burden and response to therapy. The mean value of sIL-2R in patients with acute lymphoblastic leukemia [ALL] was significantly higher than the controls. It was also significantly high in the patients with activity as compared with those at remission. Patients with chronic lymphocytic leukemia [CLL] had significantly elevated sIL-2R compared with the controls. The mean value of sIL-2R in the newly diagnosed cases of CLL was significantly higher than that of the group under treatment. There was no significant difference in the mean value of sIL-2R on comparing patients with stage I CLL to those with stage II. There was a significant difference between patients with stage I CLL and those with stage IV and between patients with stage II and stage IV. Newly diagnosed cases had a significantly high mean serum value of sIL-2R compared with those under treatment. Also, patients under treatment showed a significantly high mean serum value of sIL-2R compared with those at remission. Thus, it is clear that measurements of serum sIL-2R in patients with ALL, CLL, non-Hodgkin's lymphoma [NHL] and Hodgkin's lymphoma [HL] could offer a useful marker for tumor burden, prognosis and monitoring of treatment

Soluble interleukin-2 receptor [sIL-2R] in some hematologic malignancies

The aim of this study was to evaluate serum levels of sIL-2R in some of the hematologic malignancies and to find out if it could be a predictive marker of tumor burden and response to therapy. The mean value of sIL-2R in ALL was significantly elevated than in the controls. It was also significantly high in the patients with activity as compared with those at remission. Also, the mean value of sIL-2R in NHL was significantly elevated compared with the controls. Newly diagnosed cases had a high mean serum value of sIL-2R compared with those under treatment and a more significant elevation in comparison with the cases at remission. Also, patients under treatment showed a significantly higher mean serum value of sIL-2R than patients at remission. In patients with HL the mean value of sIL-2R was significantly elevated as compared with the controls. Newly diagnosed cases with HL had a significantly high mean serum value of sIL-2R as compared with patients under treatment and at remission. Also, patients under treatment showed a significantly high mean serum value of sIL-2R compared with those at remission

T cell responses in Hodgkin's disease: frequency distribution of IL-2 producing cells and quantitation of IL-2 produced per cell.

T cell dysfunction in Hodgkin's disease (HD) is well documented. Since interleukin-2 (IL-2) plays a pivotal role in T cell proliferation, we have investigated frequency distribution of IL-2 producing phytohaemagglutinin (PHA)-stimulated lymphocytes from HD patients compared to that of healthy donors using two limiting dilution (LD) culture systems in which autologous peripheral blood lymphocytes (PBL) and Epstein Barr Virus transformed allogeneic B lymphoblastoid cell lines (EBV-LCL) have been used as feeders. The latter provided better conditions for IL-2 production by single cells, as evident from the enhanced frequencies obtained (For healthy donors: 1/67 +/- 1545.5 using EBV-LCL and 1/1123 +/- 1.7438 using autologous PBL as feeders). The data showed significantly reduced frequency of IL-2 producing cells as well as reduced quantity of IL-2 produced per cell in HD even after using/EBV-LCL as feeders, the amount of IL-2 produced per activated responder cell in HD patients being 0.825-1.3 pg/well (p < 0.001) as compared to 1.48-2.43 pg/well in healthy donors. Thus, the EBV-LCL feeders did provide better culture conditions for estimating frequencies of functional T cells. However these cell lines were unable to restore in vitro the abnormalities in functional properties of T cells in HD.

Follow up of alterations in thyroid hormones and thyrotropin in patients of Hodgkin's disease given mantle radiation.

Thirty five patients with Hodgkin's disease who had received mantle radiotherapy to the neck were investigated for thyroid dysfunction serially over many years post radiation. No incidence of clinical hypothyroidism was noted; however, biochemical hypothyroidism (raised TSH, normal T3 and T4) was seen at some time during follow up in 22 patients. Thirteen had high TSH values at the first post radiation examination: in 6 they remained high during follow up and in seven they fell to normal or near normal without thyroxine substitution at any time. TSH abnormalities were seen by 2-3 years post radiotherapy and the return to normal, when it occurred, was seen by 4-6 years. It is advisable to follow up patients with abnormal TSH values following mantle radiation for a further 2-3 years and begin thyroxine substitution only if TSH abnormalities persist.

El sistema monocito-macrófago en la enfermedad de Hodgkin / The monocyte-macrophage system in Hodgkin's disease

La enfermedad de Hodgkin (EH) se caracteriza por la aparición de un tumor en los ganglios linfáticos constituido por una gran variedad de células que se asemejan a una reacción inflamatoria inespecífica. Las células de Reed-Sternberg (R-S) presentes en la granuloma tienen características citogenéticas, de cultivo y de heterotransplantabilidad que parecen neoplásicas. Su origen más probable es en las células interdigitantes ganglionares derivadas de los macrófagos. Al ser el ganglio linfático un órgäo inmunológico, sus alteraciones se manifestan en defectos de la respuesta inmune, los cuales pueden deberse tanto a la expresión de la calidad de las mismas. En la EH la alteración de la respuesta inmune se observa en estadíos precoces, aún con una mínima extensión de compromiso ganglionar, lo que sugiere más una lesión cualitativa que cuantitativa. Teniendo en cuenta que el origen más probable de esta extraña neoplasia es la célula de R-S y que ésta deriva de los macrófagos, investigamos la capacidad funcional de los monocitos sanguíneos transformados in vitro en macrófagos. Se estudió su capacidad fagocítica y lítica a través de la generación de productos tóxicos del oxígeneo, medidos por quimioluminiscencia y citomorfologia. Se encontró un defecto en la generación de productos tóxicos del oxígeno, que se debía a un exceso en la producción de PGE2 y era corregido por inhibidores de la síntesis de prostaglandinas (ciclooxigenasas); este defecto aparece precozmente en la EH y continúa...