RESUMO
BACKGROUND: We analyzed the results of the LMB-89 protocol performed in seven centers in Venezuela in 96 children having B-cell non-Hodgkin lymphoma treated from 1995 to 2002. PROCEDURE: Mean age was 7.1 years with 71 (74%) been male. Eighty-two patients (85%) had diffuse small cell lymphoma Burkitt and Burkitt-like, and 14 (15%) had diffuse large B-cell lymphoma. Initial disease sites included the abdomen in 67%, peripheral nodes in 8%, and mediastinal in 4%. Treatment was directed to risk groups as described for LMB-89 protocol. Group A: seven patients (7%), group B: 80 patients (83%), and group C: nine patients (9%). RESULTS: Mean follow-up was 35 +/- 31 months. Complete remission (CR) occurred in 70 patients (73%); four patients (6%) had relapse during the first year and ten patients (10%) had progressive disease. Overall survival (OS) and event free survival (EFS) were 85 and 80% at 1 year, and 82 and 75% at 2 years, respectively. The EFS by therapeutic groups at 3 years was A: 100%; B: 76%, and C: 56%. TOXICITY: neutropenia in 75%, thrombocytopenia in 63%, febrile neutropenia in 39%. Viral infections: hepatitis B in 20%, hepatitis C in 2%, and Herpes zoster in 3%. Tumor lysis syndrome (TLS) occurred in 9% during induction phase with a high mortality of 44% (urate-oxidase was available only at the end of the study). CONCLUSIONS: The high mortality rate during induction phase prohibited a better EFS. Prophylactic use of xantine-oxidase may improve future results. The high incidence of hepatitis B requires a vaccination program.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma de Células B/tratamento farmacológico , Linfoma não Hodgkin/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Criança , Ciclofosfamida/administração & dosagem , Citarabina/administração & dosagem , Progressão da Doença , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Hepatite B/complicações , Hepatite B/prevenção & controle , Vacinas contra Hepatite B/administração & dosagem , Humanos , Hidrocortisona/administração & dosagem , Leucovorina/administração & dosagem , Linfoma de Células B/patologia , Linfoma não Hodgkin/patologia , Masculino , Metotrexato/administração & dosagem , Prednisona/administração & dosagem , Recidiva , Resultado do Tratamento , Venezuela , Vincristina/administração & dosagemRESUMO
Se presentan los resultados obtenidos en 46 niños tratados en la unidad de linfomas del Hospital Universitario de Caracas con el esquema EBV más Rt a bajas dosis. Veinticuatro se trataron entre enero 1988-diciembre de 1990 con el EBV-1 (epirubicina 30 mg/m² yviblastina 6 mg/m² los días 1 y 15, cada 4 semanas) yveintidós se trataron entre enero 1991-diciembre 1994 con el EBV-2, cuya diferencia con el anterior fue el incremento de las dosis de epirubicina a 6o mg/m²Las características clínicas e histológicas de los grupos fueron similares. Se consideraron factores pronósticos (FP): los estadios clínicos III Y IV, la masa medistinal mayor del 30 por ciento del diámetro torácico, los síntomas B y el volumen tumoral mayor de 5 cm. Los pacientes con 0 ó 1 FP se ubicaron en el grupo favorable y recibieron 4 ciclos de Qt, combinados en ambos grupos con Rt: 20-25 C y a zonas afectas. Se obtuvo remisión completa en el 76 por ciento de los pacientes y sobrevidas libre de enfermedad, libre de eventos y total de 84 por ciento, 68 por ciento y 78 por ciento respectivamente a los 5 años de seguimiento. No se observaron diferencais significativas en los resultados obtenidos con el EBV-1 y el EBV-2, pero fueron superiores en el grupo favorable. La Qt fue bien tolerada y pudo administrarse ambulatoriamente. Los efectos tóxicos tardíos fueron hipotiroidismo subclínico en 5/14 pacientes (36 por ciento), carcinoma de tiroides en 1/46 (2 por ciento) y cardiomiopatía dilatada en 1/46 (2 por ciento) tratado con EBV-2. Concluimos que 4 ciclos de EBV-1 combinados con Rt. a bajas dosis es una alternativa efectiva en el tratamiento de los niños con E.H grupo favorable y que el incremento de la dosis de epirubicina a 60 mg/m² no mejora los resultados
Assuntos
Humanos , Criança , Radioterapia , Doença de Hodgkin , Tratamento Farmacológico/classificação , Tratamento Farmacológico/efeitos adversos , CriançaRESUMO
In order to clarify the mechanisms of the eosinophilia frequently observed in patients with Hodgkin's disease (HD), 18 patients and 16 age- and sex-matched controls were studied. Increased eosinophil numbers in peripheral blood and serum IgE, as well as decreased cell-mediated immunity were present in HD patients compared with control individuals. Advanced disease was accompanied by lower eosinophil levels, increased IgE, and lower CD4+ T cell counts in peripheral blood. Eosinophilia correlated with CD4+ T cell counts, suggesting that eosinophil production could be under CD4+ T cell control. GM-CSF production in vitro by Phytohemagglutinin-stimulated mononuclear cells was significantly lower in HD patients with eosinophilia. On the other hand, an eosinophil-survival-enhancing activity was found in sera and culture supernatants from controls and HD patients; this activity was stronger for HD patients and was higher for those with eosinophilia. Furthermore, this activity was completely abolished by preincubation with monoclonal antibodies to IL-5, but not with normal mouse serum. Our results suggest that defects of cell-mediated immunity present in patients with HD are accompanied by a predominant type 2 cytokine profile. IL-5 is involved in the increased eosinophil production observed in these patients.
Assuntos
Eosinofilia/imunologia , Doença de Hodgkin/imunologia , Interleucina-5/fisiologia , Adolescente , Adulto , Idoso , Sobrevivência Celular/imunologia , Fezes/parasitologia , Feminino , Doença de Hodgkin/sangue , Humanos , Hipersensibilidade Imediata/imunologia , Imunidade Celular , Imunoglobulina E/sangue , Contagem de Leucócitos , Masculino , Pessoa de Meia-IdadeRESUMO
Natural killer (NK) cytotoxic activity was simultaneously investigated in bone marrow mononuclear cells (BMMC) and peripheral blood lymphocytes (PBL) from nine Hodgkin's disease (HD) and 15 non-Hodgkin lymphoma (NHL) untreated patients. Twenty-five PBL samples and seven bone marrow specimens from healthy individuals were also included as control group (C). NK cell activity was evaluated in basal condition and post-stimulation with human recombinant IL-2 (rIL-2). Data were expressed in K values (number of BMMC or PBL needed to lyse 50% of the target cells). In basal condition, both HD and NHL patients showed a NK cell activity comparable to the C group, both in BMMC (HD, K = 2.48 +/- 1.3; NHL, K = 3.8 +/- 2.0; C, K = 3.2 +/- 0.7) and PBL (HD, K = 2.0 +/- 1.0; NHL, K = 2.3 +/- 1.0; C, K = 2.2 +/- 0.2). Stimulation with rIL-2 induced a significant and comparable enhancement of the NK activity in PBL from HD, NHL and C while the response to rIL-2 of the BMMC in most of the HD and NHL patients was significantly greater than the C group. Responder cells were characterized by negative selection with specific MoAb plus complement as a CD3-, CD16+, CD56+ cytotoxic cell and further confirmed by flow cytometry. We postulate that IL-2 activation of bone marrow NK cell precursors, in addition to enhancing the activity of circulating NK, may be of value for the therapeutic rationale of IL-2 in patients with lymphoma.
Assuntos
Medula Óssea/imunologia , Interleucina-2/farmacologia , Células Matadoras Naturais/imunologia , Linfoma/imunologia , Adolescente , Adulto , Idoso , Antígenos CD/fisiologia , Antígenos de Diferenciação de Linfócitos T/fisiologia , Complexo CD3 , Antígeno CD56 , Criança , Citotoxicidade Imunológica , Humanos , Células Matadoras Naturais/efeitos dos fármacos , Pessoa de Meia-Idade , Receptores de Antígenos de Linfócitos T/fisiologia , Proteínas Recombinantes/farmacologiaRESUMO
Twenty-five patients with Hodgkin's disease and high eosinophil counts were observed for an average of 90 months. Fluctuations in the levels of eosinophils were important in the course of observation. No relation with stages, histologic type, or evolution was noticed. Steroid-containing regimens and severe premortem conditions seemed to lower the counts. Relapse-free survival was shorter in our 25 patients than in a control group of 50 patients with Hodgkin's disease and no eosinophilia who had approximately the same stage, histologic type, and treatment of disease. However, the overall survival was somewhat better for the eosinophilic patients with stages IIIB and IV (0.1 greater than P greater than 0.05).
Assuntos
Eosinofilia/sangue , Doença de Hodgkin/sangue , Adolescente , Adulto , Criança , Eosinófilos , Feminino , Seguimentos , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/mortalidade , Doença de Hodgkin/patologia , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Taxa de SobrevidaRESUMO
En el presente estudio se evaluó la SP y MO de 21 pacientes, no tratados con diagnóstico de linfoma y provenientes de la Unidad de Linfomas del Hospital Universitario de Caracas. El protocolo de investigación incluyó parámetros clínicos e histológicos. En los grupos estudiados se evaluó el porcentaje de células killer naturales (NK) mediante el uso de anticuerpos monoclonales, así como la actividad NK basal postestimulación in vitro con 500/ml de IL 2. Los resultados muestran que los porcentajes de células en SP y MO son similares en pacientes con EH y LNH en relación al grupo de control