RESUMO
Clinical benefit in oncology patients can only be derived from coordinated and successive experimental trials. The following consensus thus emerged from the working party: The assessment of tolerance during clinical trials requires the actuarial rate of acute adverse events (AE) to be registered and the development of epidemiological structures involved in long-term assessment of AE. Experimental trials have to be assessed according to descriptive epidemiological data (generated in France and Europe) and completed with observational studies on post-marketing medical practice. The principle of an a priori authorization given by the Afssaps for gene and cell therapy trials was legalised in October 2001. The working group spoke strongly in favour of authorizing early trials only validating the process, and for reasonable objectives in terms of viral security assessment of annex therapeutic products. With regard to the development of new antiproliferative agents, the active dose (or optimal biological dose) replaces the maximal tolerable dose. Early efficacy criteria could be biological and specific. With cumulative subacute rather than acute toxicity, these agents can not be properly evaluated with a short term benefit/risk ratio as is done for cytotoxic drugs. Elderly people constitute a fragile, heterogeneous and increasing population, in whom adequate assessment of anticancer agents is mandatory. It is important to promote controlled clinical trials in children and to systematically monitor them over a very long period of time. Only rare tumours may be considered as orphan situations. Finally, a list of all clinical trials conducted in oncology should be made by the Afssaps, with the help of the FNLCC (Fédération Nationale des Centres de Lutte Contre le Cancer) who have already begun this work.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias/tratamento farmacológico , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Ensaios Clínicos como Assunto , Humanos , Projetos de PesquisaAssuntos
Transplante de Medula Óssea/efeitos adversos , Eosinofilia/etiologia , Linfoma de Células T/etiologia , Mieloma Múltiplo/terapia , Segunda Neoplasia Primária/etiologia , Adulto , DNA de Neoplasias/genética , Eosinofilia/genética , Humanos , Linfoma de Células T/genética , Masculino , Segunda Neoplasia Primária/genética , Fatores de Tempo , Doadores de Tecidos , Transplante HomólogoRESUMO
We report three cases of typical aplastic anaemia (AA) associated with a Philadelphia chromosome. This translocation was detected at the time of diagnosis of AA (one patient) and when overt leukaemia was diagnosed (two patients: one chronic myeloid leukaemia and one acute lymphoblastic leukaemia) after AA therapy and recovery of blood counts. We discuss the literature arguments about considering some cases of AA as preleukaemic disorders and suggest that our cases illustrate the association of AA with a clonal malignant disorder. We conclude that cytogenetic analysis is necessary at diagnosis of AA or after recovery of blood counts.
Assuntos
Anemia Aplástica/genética , Cromossomo Filadélfia , Pré-Leucemia/genética , Adulto , Anemia Aplástica/complicações , Análise Citogenética , Feminino , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/complicações , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/genéticaRESUMO
PURPOSE: To conduct a prospective study of primary lymphoma of bone (PLB) comparatively with extraskeletal non-Hodgkin's lymphomas (ESNHLs) and secondary lymphoma of bone (SLB). PATIENTS AND METHODS: The 28 cases of PLB, 2932 cases of ESNHL, and 219 cases of SLB included between April 1, 1993, and October 1, 1997, in a treatment protocol for NHL developed by the Adult Lymphoma Study Group, were studied prospectively. RESULTS: Of the 28 PLB patients, 17 were men and 11 women; median age was 48 years (range, 18-69). The disease was monostotic in 17 cases (involving the peripheral skeleton in 14) and polyostotic in nine cases. The proportion of patients younger than 60 years was 86% in the PLB group, 59% in the ESNHL group, and 55% in the SLB group. The Ann Arbor stage distribution (I-II/III-IV) was as follows: 54%/46% in the PLB group, 50%/50% in the ESNHL group, and 20%/80% in the SLB group. Performance status was 0 or 1 in 100% of the PLB patients, 50% of the ESNHL patients, and 20% of the SLB patients. The phenotype was B in 89% of the PLBs and 85% of the ESNHLs and SLBs. In the PLB group, 54% of patients had diffuse large cell tumors and 11% diffuse mixed tumors; in the ESNHL group, 39% had diffuse large cell, 13% diffuse mixed, and 8% diffuse immunoblastic tumors; and in the SLB group, 45% had diffuse large cell, 10% diffuse mixed, and 12% diffuse immunoblastic tumors. A complete or partial response to induction therapy was noted in 86% of PLB patients, 84% of ESNHL patients, and 78% of SLB patients. Overall five-year survival was 65% in the PLB group, 50% in the ESNHL group, and 40% in the SLB group. DISCUSSION: Survival was better in the PLB group. Further studies are needed to determine the effect of radiation therapy at completion of the treatment protocol and to look for prognostic factors associated with bone involvement.
Assuntos
Neoplasias Ósseas/patologia , Linfoma/patologia , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bleomicina/administração & dosagem , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/mortalidade , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Humanos , Linfoma/tratamento farmacológico , Linfoma/mortalidade , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/patologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prednisona/administração & dosagem , Estudos Prospectivos , Inquéritos e Questionários , Taxa de Sobrevida , Resultado do Tratamento , Vindesina/administração & dosagemAssuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Fator Estimulador de Colônias de Granulócitos/efeitos adversos , Fator Estimulador de Colônias de Granulócitos e Macrófagos/efeitos adversos , Linfoma não Hodgkin/tratamento farmacológico , Fibrose Pulmonar/etiologia , Adulto , Idoso , Bleomicina/administração & dosagem , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Quimioterapia Combinada , Evolução Fatal , Feminino , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Fator Estimulador de Colônias de Granulócitos e Macrófagos/uso terapêutico , Humanos , Masculino , Metotrexato/administração & dosagem , Metilprednisolona/administração & dosagem , Pessoa de Meia-Idade , Estudos Retrospectivos , Vindesina/administração & dosagemRESUMO
Leukemic T-LGL (large granular lymphocyte) composed of clonal CD3+ TCR alphabeta+ CD8+ CD57+ cells were compared with oligoclonally CD3+ CD8hi+ CD57- lymphocytes expanded after BMT. Leukemic CD3+ CD8hi+ CD57+ LGL showed several phenotypic differences such as an upregulation of CD16 and adhesion molecules (mainly CD11c, CD58 and CD54), activation markers and an exclusive CD45RA isoform expression. Unstimulated CD3+ CD8+ CD57+ LGL from both leukemic and BMT donors spontaneously developed an ex vivo CTL-like CD3-redirected cytotoxicity but no NK cell activity. Different stimuli (PHA, PMA or rhIL-2) induced similar cytotoxic profiles after a 6-day culture involving a CD3-redirected lysis predominating over a low NK cell activity. However, culture of leukemic LGL with these stimuli allowed either a 2 week persistence (PMA or rhIL-2) of CD8+ CD57+ LGL or their disappearance after 3 days (PHA). Furthermore, leukemic CD8hi+ CD57+ T lymphocytes produced an inhibitor of cytotoxic functions as previously described for BMT recipients' CD8+ CD57+ cells. Thus, despite some phenotypic differences between both cell sources, leukemic CD57+ T-LGL display the same functional characteristics of cytotoxic effector and immunoregulatory T cells as CD8+ CD57+ T cells from BMT recipients which might represent their normal counterpart.
Assuntos
Transplante de Medula Óssea , Complexo CD3/sangue , Antígenos CD57/sangue , Antígenos CD8/sangue , Leucemia Linfoide/terapia , Estudos de Casos e Controles , Feminino , Humanos , Imunofenotipagem , Interleucina-2/uso terapêutico , Leucemia Linfoide/imunologia , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes/uso terapêutico , Estimulação QuímicaRESUMO
Although widely used, non-steroidal anti-inflammatory drugs (NSAIDs) are associated with a high incidence of gastrointestinal (GI) side-effects. Inhibition of the cyclooxygenase (COX) enzyme is the basis for both the efficacy and toxicity of NSAIDs. The discovery of two COX isoforms, constitutive COX-1 and inducible COX-2, has led to the hypothesis that selective inhibition of COX-2 will minimize the potential for GI toxicity without compromising efficacy. The Meloxicam Large-scale International Study Safety Assessment (MELISSA) trial reported here was therefore set up to investigate the tolerability of meloxicam, a preferential inhibitor of COX-2, compared to diclofenac. MELISSA was a large-scale, double-blind, randomized, international, prospective trial, conducted over 28 days in patients with symptomatic osteoarthritis. Patients received either meloxicam 7.5 mg or diclofenac 100 mg slow release, the recommended doses for the treatment of osteoarthritis. Evaluation of the profile of adverse events was the main aim of the trial, together with assessment of efficacy. A total of 9323 patients received treatment (4635 and 4688 in the meloxicam and diclofenac groups, respectively). Significantly fewer adverse events were reported by patients receiving meloxicam. This was attributable to fewer GI adverse events (13%) compared to diclofenac (19%; P < 0.001). Of the most common GI adverse events, there was significantly less dyspepsia (P < 0.001), nausea and vomiting (P < 0.05), abdominal pain (P < 0.001) and diarrhoea (P < 0.001) with meloxicam compared to diclofenac. Five patients on meloxicam experienced a perforation, ulcer or bleed vs seven on diclofenac (not significant). No endoscopically verified ulcer complication was detected in the meloxicam group compared to four with diclofenac. There were five patient days of hospitalization in patients on meloxicam compared to 121 with diclofenac. Adverse events caused withdrawal from the study in 254 patients receiving meloxicam (5.48%) compared to 373 (7.96%) on diclofenac (P < 0.001). These differences were attributable to differences in reported GI adverse events (3.02% on meloxicam vs 6.14% on diclofenac; P < 0.001). Differences in efficacy, as assessed by visual analogue scales, consistently favoured diclofenac. In all instances, 95% confidence intervals did not cross zero, suggesting a statistically significant effect. However, differences were small (4.5-9.01% difference) and did not reach pre-determined levels of clinical significance. Nevertheless, significantly more patients discontinued meloxicam because of lack of efficacy (80 out of 4635 vs 49 out of 4688; P < 0.01). The MELISSA trial confirms earlier studies suggesting that meloxicam has a significantly improved GI tolerability profile in comparison with other NSAIDs, including diclofenac. These results may in part reflect the preferential COX-2 selectivity of meloxicam, although the dose and other aspects of tolerability may be important. These results may provide support for the hypothesis that selective inhibition of COX-2 relative to COX-1 might be an effective approach towards improved NSAID therapy.
Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Inibidores de Ciclo-Oxigenase/efeitos adversos , Diclofenaco/efeitos adversos , Gastroenteropatias/induzido quimicamente , Osteoartrite/tratamento farmacológico , Tiazinas/efeitos adversos , Tiazóis/efeitos adversos , Idoso , Anti-Inflamatórios não Esteroides/uso terapêutico , Inibidores de Ciclo-Oxigenase/uso terapêutico , Diclofenaco/uso terapêutico , Método Duplo-Cego , Feminino , Gastroenteropatias/classificação , Hemorragia Gastrointestinal/induzido quimicamente , Humanos , Isoenzimas/antagonistas & inibidores , Masculino , Meloxicam , Pessoa de Meia-Idade , Pacientes Desistentes do Tratamento/estatística & dados numéricos , Úlcera Péptica/induzido quimicamente , Estudos Prospectivos , Tiazinas/uso terapêutico , Tiazóis/uso terapêutico , Resultado do TratamentoRESUMO
SELECT is a large-scale, prospective, international, multicentre, double-blind, double-dummy, randomized, parallel-group trial. Patients with exacerbation of osteoarthritis were treated with the recommended dose of meloxicam (7.5 mg) or piroxicam (20 mg) once daily for 28 days; 4320 patients were administered meloxicam and 4336 piroxicam. The incidence of adverse events was significantly lower in the meloxicam group (22.5%) compared with the piroxicam group (27.9%; P < 0.001), mainly due to the significantly lower incidence of gastrointestinal (GI) adverse events in the meloxicam than in the piroxicam group (10.3% vs 15.4%,; P < 0.001), while the efficacy of both drugs was equivalent. Individual GI events occurred significantly less often with meloxicam than piroxicam: dyspepsia (3.4% vs 5.8%; P < 0.001), nausea/vomiting (2.5% vs 3.4%; P < 0.05) and abdominal pain (2.1% vs 3.6%; P < 0.001). There were 16 patients with perforations, ulcerations or bleeding (PUBs) of the upper GI tract in the piroxicam group compared with seven in the meloxicam group (relative risk piroxicam:meloxicam = 1.4). Four PUBs were complicated (perforations or bleedings); none of these occurred in the meloxicam group (relative risk piroxicam:meloxicam = 1.9). The outcome of SELECT is consistent with that of the large-scale clinical trial of similar design and size which compared 7.5 mg meloxicam with 100 mg diclofenac in patients with osteoarthritis, and with a previous global analysis of the safety of meloxicam. It adds further data to the proposed relationship between selective inhibition of cyclooxygenase-2 and improved GI tolerability of non-steroidal anti-inflammatory drugs.
Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Inibidores de Ciclo-Oxigenase/efeitos adversos , Gastroenteropatias/induzido quimicamente , Osteoartrite/tratamento farmacológico , Piroxicam/efeitos adversos , Tiazinas/efeitos adversos , Tiazóis/efeitos adversos , Idoso , Anti-Inflamatórios não Esteroides/uso terapêutico , Inibidores de Ciclo-Oxigenase/uso terapêutico , Método Duplo-Cego , Feminino , Humanos , Isoenzimas/antagonistas & inibidores , Masculino , Meloxicam , Pessoa de Meia-Idade , Piroxicam/uso terapêutico , Estudos Prospectivos , Tiazinas/uso terapêutico , Tiazóis/uso terapêutico , Resultado do TratamentoRESUMO
PURPOSE: The impact of treatment options on survival and late neurologic toxicity was investigated in a series of patients with primary cerebral lymphoma (PCL) and no known cause of immunosuppression. PATIENTS AND METHODS: Prognostic factors for survival and treatment-induced late neurotoxicity were investigated in a retrospective series of 226 patients with PCL. RESULTS: With a median follow-up of 76 months, the median overall survival was 16 months and 5-year survival was 19%. In a univariate analysis, age greater than 60 years, performance status, CSF protein level greater than 0.6 g/L, involvement of corpus callosum or subcortical grey structures, detectable lymphoma cells in CSF, increased serum lactate dehydrogenase (LDH), but not histological subtype, were significantly correlated with a poor survival. Treatment with chemotherapy versus radiotherapy alone (P = .05), high-dose methotrexate (HDMTX; P = .0007), and cytarabine (P = .04) correlated with a better survival in univariate analysis. Using the Cox model, age, performance status, and CSF protein were independently correlated with survival. After adjustment of these factors, treatment with an HDMTX-containing regimen remained the only treatment-related factor independently correlated with survival (P = .01). The projected incidence of treatment-induced late neurotoxicity was 26% at 6 years in this series, with a median survival from the diagnosis of late neurotoxicity of 12 months. Treatment with radiotherapy followed by chemotherapy was the only parameter correlated with late neurotoxicity in multivariate analysis (relative risk, 11.5; P = .0007). CONCLUSION: Patients with PCL treated with regimens that included HDMTX followed by radiotherapy have an improved survival, but not a higher risk of late neurotoxicity as compared with other treatment modalities in this series.
Assuntos
Antimetabólitos Antineoplásicos/efeitos adversos , Neoplasias Encefálicas/tratamento farmacológico , Linfoma/tratamento farmacológico , Metotrexato/efeitos adversos , Adolescente , Adulto , Idoso , Antimetabólitos Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/radioterapia , Criança , Terapia Combinada , Irradiação Craniana , Esquema de Medicação , Feminino , Humanos , Linfoma/radioterapia , Masculino , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Análise de SobrevidaRESUMO
THE SURVEY: To better ascertain diagnostic and treatment strategies used by physicians for idiopathic thrombocytopenic purpura, a questionnaire was addressed to 298 French hematologists and pediatricians. One hundred and ten responses were analyzed. DIAGNOSTIC APPROACH: Thrombocytopenia was determined on capillary blood samples by 50% of the physicians and platelet-associated antibody by 44%. Bone marrow aspirates were obtained more frequently in adults (85%) than in children (47%) and immune disorders were more often investigated in 95% of adults and in 68% of children. THERAPEUTICS: Treatment threshold was lower in children (20.10(9)/l) than in adults (50.10(9)/l). Corticoidsteroids was the treatment of choice in adults (98%) and children received either IV immunoglobulins (61%) and/or corticosteroids (63%); higher doses were used in children (> or = 2 mg/kg versus 1 mg/kg) for shorter periods (> or = 2 weeks versus > 3 weeks). Treatment failure was evaluated earlier in children (< 10 days) than in adults (> 20 days). RECOMMENDATIONS: 1. Diagnosis. Based on repeatedly low platelet counts and verification that only platelets are involved. Clinical examination is normal excepting rare cases of severe hemorrhage. Search for antiplatelet antibodies is non-contributive 2. Treatment Short-term corticosteroids, both in children and adults. Intravenous gammaglobulins should be limited to cases with signs of severe hemorrhage. 3. Consult the complete guidelines for each individual clinical situation.
Assuntos
Púrpura Trombocitopênica Idiopática/diagnóstico , Humanos , Púrpura Trombocitopênica Idiopática/etiologia , Púrpura Trombocitopênica Idiopática/terapia , Inquéritos e QuestionáriosRESUMO
Among non-Hodgkin's lymphomas, primary mediastinal large B-cell lymphoma (PMLCL) has been considered a separate entity that has specific clinical and histological aspects and a poor prognosis. In this study, we reexamined the clinicopathologic features and the response to current treatment of 141 PMLCL and compare them with 916 nonmediastinal large B-cell lymphomas (NMLCL) recorded in the same period and treated with similar combined chemotherapy. The clinical features of PMLCL at diagnosis were largely homogeneous and distinct from NMLCL, with a predilection for young women (59% with a mean age of 37 years versus 42% with a mean age of 54 years), bulky tumor (77% versus 7%, p < 10(4)), high serum lactic dehydrogenase (LDH) level 76% versus 51%, p < 10(4)), and frequent intrathoracic extension to adjacent organs such as pleura, pericardium, and lung. By contrast, extrathoracic or hematologic dissemination was uncommon (2% of bone marrow involvement versus 17%). All patients had diffuse large B-cell nonimmunoblastic, nonanaplastic lymphomas. Histological analysis of the 141 PMLCL evaluated two common patterns: the presence of large cells with clear cytoplasm (found in 38% of cases) and the presence of fibrosis (marked in 25% of cases). The presence of clear cells or intense fibrosis did not constitute prognostic indicators. Immunologic and molecular analysis assessed the profile of bcl-2 expression and the presence of Epstein-Barr virus (EBV) in PMLCL: 30% expressed a high level of bcl-2 protein; EBER RNAs were detected by in situ hybridization in only two of the 41 cases tested. Monotypic light chain restriction could be demonstrated in seven of the 41 PMLCL tested on fixed-section. Treated with polychemotherapy regimens without radiotherapy, 79% of PMLCL patients achieved a complete remission compared with 68% in the NMLCL patient group (p = 0.01). Overall, 3-year survival rates were estimated at 66 and 61%, respectively (p = 0.05), and disease-free survival rates were not significantly different (61 versus 64%). Stratified analysis on the International Prognostic Index (based on age, tumor stage, serum LDH level, and performance status) showed no difference in the overall and disease-free survivals between the two lymphoma groups. In conclusion, PMLCL can be combined with other diffuse large B-cell lymphomas on morphologic grounds; it is not associated with EBV. It responds favorably to treatment and should be managed like other high-grade lymphomas of equivalent histology. However, the uncommon clinical presentation makes it a distinct entity.
Assuntos
Linfoma de Células B/patologia , Linfoma Difuso de Grandes Células B/patologia , Neoplasias do Mediastino/patologia , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estudos de Coortes , Feminino , França , Herpesvirus Humano 4/isolamento & purificação , Humanos , Imuno-Histoquímica , L-Lactato Desidrogenase/sangue , Linfoma de Células B/tratamento farmacológico , Linfoma de Células B/virologia , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/virologia , Masculino , Neoplasias do Mediastino/tratamento farmacológico , Neoplasias do Mediastino/virologia , Pessoa de Meia-Idade , PrognósticoRESUMO
Merkel cell carcinoma is a neuroendocrine primitive tumor of the skin. We report a case who develops node and visceral metastasis, and dead. The clinical presentation, diagnosis, histology, immunocytochemistry, treatment and prognosis of this tumor will be discussed.
Assuntos
Carcinoma de Célula de Merkel , Neoplasias Cutâneas , Carcinoma de Célula de Merkel/mortalidade , Carcinoma de Célula de Merkel/patologia , Carcinoma de Célula de Merkel/terapia , Feminino , Humanos , Pessoa de Meia-Idade , Prognóstico , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/terapiaRESUMO
The cause of the rare and severe condition of aplastic anaemia is largely unknown, although certain drugs have been implicated as possible aetiological factors, mostly through the evidence of case reports. A case-control study was conducted in metropolitan France between 1985 and 1988 to investigate aetiological factors in aplastic anaemia. It was conducted in parallel with the establishment of a national register of the incidence of aplastic anaemia, which started in May 1984. The controls used in the study consisted of 2 hospitalized controls (i.e. patients admitted to hospital at the same time as the case) and a neighbour control named by the case. All three controls were matched for age and sex, and were interviewed by the same investigator as the case. A total of 147 cases, 287 hospitalized controls and 108 neighbour controls were interviewed. An association of varying degrees was noted between aplastic anaemia and the following conditions or treatments: clinical hepatitis during the past 6 months; history of chronic immune disorder (mainly rheumatoid arthritis); gold salts and D-penicillamine; colchicine and allo-thiopurinol; acetaminophen and salicylates. This survey confirmed the vanishing role of previously known toxic agents in the aetiology of aplastic anaemia. Some differences observed between the results of the present study and those published previously suggest that targeted studies on each category of drug according to specific disease areas should be initiated.
Assuntos
Anemia Aplástica/induzido quimicamente , Anemia Aplástica/epidemiologia , Estudos de Casos e Controles , Feminino , França/epidemiologia , Humanos , Incidência , Masculino , Prevalência , Sistema de RegistrosRESUMO
BACKGROUND: Based on the national register of new cases of aplastic anaemia (AA) begun in France in 1984, a case-control study was conducted to explore the aetiology of the disease. METHODS: Cases were all included in the French national register of AA. Two different groups of controls were derived with individual matching; one group from hospitalized patients in the same hospital; the other group from neighbours named by the case. A 15-year occupational history was collected through interview and then grouped into exposure categories by jobs done for one year or more. The study included 98 cases, 181 hospitalized controls, and 72 neighbours aged 18-70 years. RESULTS: No differences appeared between the cases and both groups of controls relative to any group of occupation investigated. However, a borderline non-significant small excess for exposure to pesticides was observed among the cases when compared to hospitalized controls. Whatever the control group, no association was found between AA and exposure to solvents, ionizing radiation, fuel, oils and grease. A positive relationship between exposure to glues and AA was observed, as well as a trend towards an increased risk after exposure to paints. CONCLUSIONS: This large-scale case-control study confirmed the vanishing role of previously known toxic substances in the aetiology of AA. However, a higher proportion of AA patients reported exposure to paints and to glues, a relationship which needs further investigation because of the diversity of compounds included in these products.
Assuntos
Anemia Aplástica/etiologia , Exposição Ocupacional/efeitos adversos , Adulto , Idoso , Anemia Aplástica/epidemiologia , Estudos de Casos e Controles , Feminino , França/epidemiologia , Hospitalização , Humanos , Modelos Logísticos , Masculino , Análise por Pareamento , Pessoa de Meia-Idade , Ocupações , Razão de Chances , Fatores de RiscoRESUMO
Monosomy 7 was detected in bone marrow cells from three patients, one with myeloid leukemia, and two others with myelodysplastic syndrome following previous chemotherapy. Fluorescence in situ hybridization (FISH), carried out with an alphoid DNA probe specific for chromosome 7 centromere, showed that a small marker chromosome present in the tumor cells' karyotype of the three patients, was derived from the missing chromosome 7. In two cases, the marker was a ring chromosome, whereas in the third case it was a tiny dot-like chromosome, unnoticed at first examination on R-banded metaphases. In the three cases, the marker was lost in a proportion of tumor cells. FISH experiments suggested that the marker centromere had undergone structural alterations, with a fluorescence pattern distinct from a normal one. On the whole, these data suggest that: firstly, leukemia-associated monosomy 7 results, in a proportion of cases, from a structural event rather than from simple loss of a whole chromosome 7; secondly, interpretation of interphase FISH must be cautious in monosomy 7 evaluation; and thirdly structural alteration of the chromosome 7 derivative alphoid DNA could explain its propensity to segregate unequally and to be lost at mitosis.
Assuntos
Cromossomos Humanos Par 7 , Leucemia Monocítica Aguda/genética , Monossomia , Adulto , Idoso , Marcadores Genéticos , Humanos , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/genéticaRESUMO
The authors report their experience about 8 cases of nasal lymphomas diagnosed and treated between 1987 and 1993. Behind ordinary symptoms, a very bad forecast lymphoma may be hidden. Histological diagnosis is sometimes difficult and needs voluminous fresh fragments. During the evolution of this affection, local temporary nasal and paranasal remissions are often noted after chimiotherapy and/or radiotherapy, but rapidly appear visceras secondary localisations, suggesting an underestimation of the nasal and paranasal sinuses localisations among the treated non-Hodgkin's lymphomas population.
Assuntos
Linfoma não Hodgkin , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Linfoma não Hodgkin/diagnóstico , Linfoma não Hodgkin/patologia , Linfoma não Hodgkin/terapia , Masculino , Pessoa de Meia-Idade , Cavidade Nasal , Neoplasias Nasais/diagnóstico , Neoplasias Nasais/patologia , Neoplasias Nasais/terapia , Neoplasias dos Seios Paranasais/diagnóstico , Neoplasias dos Seios Paranasais/patologia , Neoplasias dos Seios Paranasais/terapia , Fatores de TempoRESUMO
In order to describe renal involvement in aggressive non-Hodgkin's lymphomas (NHLs) and its prognostic significance, we reviewed the outcome of 48 patients with renal involvement treated with the LNH-84 or LNH-87 regimen. Histology was diffuse large cell in 29 (60%) patients; immunoblastic, diffuse mixed cell and lymphoblastic in four each; follicular large cell, diffuse small cleaved cell and diffuse small non-cleaved cell in one each; and unclassified in four. Ann Arbor stage was IV in 44 patients, and IE or IIE in four. Tumour mass > or = 10 cm, performance status (ECOG scale) > 2 and increased LDH level were present in 69%, 20% and 76% of patients respectively. Fifteen patients (31%) had multiple intraparenchymal nodules, 14 (29%) had direct spread into the kidney from a perirenal mass, ten (21%) had a single intraparenchymal nodule and nine (19%) had diffuse infiltration. Twenty-one patients (43%) presented with bilateral lesions. Three patients (6%) presented with acute renal failure. Ten other patients (21%) had serum creatinine > 120 mumol l-1. In 12 of these 13 patients renal function was restored with chemotherapy. Twenty-eight patients (57%) achieved complete remission. Estimated 4 year disease-free survival was 39%. Disease-free survival and actuarial survival at 4 years were estimated to be 58% respectively. Two renal parameters had adverse prognostic significance for survival: renal hilum involvement (P = 0.02) and diffuse renal infiltration (P = 0.01). A Cox model identified only two independent prognostic factors for survival, namely performance status > or = 2 and tumour size > or = 10 cm. We conclude that alteration in renal function occurs in 27% of patients with renal involvement. Systemic chemotherapy improves renal function rapidly. Long-term outcome is similar to that expected in NHL patients presenting with the same prognostic factors.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/secundário , Linfoma não Hodgkin/tratamento farmacológico , Análise Atuarial , Adolescente , Adulto , Idoso , Antibióticos Antineoplásicos/administração & dosagem , Bleomicina/administração & dosagem , Distribuição de Qui-Quadrado , Creatinina/sangue , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Humanos , Rim/fisiopatologia , Neoplasias Renais/fisiopatologia , L-Lactato Desidrogenase/sangue , Linfoma Folicular/tratamento farmacológico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Imunoblástico de Células Grandes/tratamento farmacológico , Linfoma não Hodgkin/patologia , Masculino , Metotrexato/administração & dosagem , Metilprednisolona/administração & dosagem , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Prednisolona/administração & dosagem , Prognóstico , Modelos de Riscos Proporcionais , Indução de Remissão , Análise de Sobrevida , Taxa de Sobrevida , Resultado do Tratamento , Vindesina/administração & dosagemRESUMO
Sixteen adult patients with relapsed (7 patients) or refractory (9 patients) acute leukemia received mitoxantrone (10 mg/m2 per day for 3 days) and etoposide (200 mg/m2 per day for 3 days) with escalating dose of cyclosporin A (CsA) from a loading dose of 2 mg to 6.5 mg/kg per 2 h followed by 3 days continuous infusion of 5-15 mg/kg per day. The major toxicities were stomatitis and prolonged aplasia, occurring for 15 mg/kg per day of CsA. Transient conjugated hyperbilirubinemia occurred in all patients, and was CsA dose-dependent (r = 0.7). Adequate serum levels of CsA (> 1 microgram/ml) were obtained in 3/6 patients treated with 10 mg/kg per day and 4/4 patients with 15 mg/kg per day. The pharmacokinetic of mitoxantrone showed an unusual increase of carboxylic metabolites, parallel to CsA levels. We observed six responses (two complete and four partial remissions), and eight resistances. Two patients died at days 3 and 8 from sepsis. Before treatment, 7/16 patients tested for P-gp with C219 were positive (> 10% positive cells). 3/6 responders were P-gp-positive. At time of leukemic regrowth, cells expressing P-gp before therapy reverted to P-gp-negative cells.