RESUMO
BACKGROUND: Elastic compression stockings (ECS) are uncomfortable to wear but may prevent post-thrombotic syndrome (PTS). The ability to predict PTS may help clinical decision making regarding the optimal duration of ECS after deep vein thrombosis (DVT). AIMS: Predefined endpoint analysis of the Octavia study that randomized patients who compliantly used ECS up to one year after DVT to continue or discontinue ECS treatment. Primary aim was to identify predictors of PTS. METHODS: Patient characteristics were collected and ultrasonography was performed to assess reflux, residual thrombosis and persistent thrombus load 12â¯months after DVT. Multivariable analyses were performed to identify factors related to PTS. RESULTS: Thrombus scoreâ¯≥â¯3, BMIâ¯≥â¯26, duration of symptoms before DVT diagnosisâ¯≥â¯8â¯days and a Villalta score of 2-4 points were statistically significant predictors of PTS. The predictive value for PTS for the assessed variables was not different between the 2 treatment groups. In the stop ECS group, 3.2% (95%CI 0.08-18) of patients without any predictors for PTS were diagnosed with mild PTS during follow-up, and none with severe PTS, for a sensitivity of 98% (95% CI 89-100), a specificity of 14% (95% CI 10-20), a positive predictive value of 20% (95% CI 19-22), and a negative predictive value of 97% (95% CI 81-100). CONCLUSION: We identified 4 predictors of PTS occurring in the 2nd year after DVT. Our findings may be used to decide on whether to continue ECS treatment for an additional year, after one year of compliant ECS use, keeping in mind that patients with none of the predictors will have the lowest PTS incidence.
Assuntos
Síndrome Pós-Trombótica/prevenção & controle , Meias de Compressão , Trombose Venosa/prevenção & controle , Idoso , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Síndrome Pós-Trombótica/diagnóstico , Síndrome Pós-Trombótica/etiologia , Prognóstico , Trombose Venosa/complicações , Trombose Venosa/diagnósticoRESUMO
Chronic lymphocytic leukemia (CLL) is the most common lymphoproliferative disorder in the western hemisphere, with an annual incidence of 3:100000. Commonly patients are asymptomatic but not rarely disease progression occurs in the setting of lymphadenopathy and extensive leukemic burden. Leptomeningeal involvement in patients with CLL is infrequent, with presenting symptoms of headache (23%), acute or chronic changes in mental status (28%), cranial nerve abnormalities (54%) including optic neuropathy (28%), weakness of lower extremities (23%) and cerebellar signs (18%). In this report, we discuss a CLL patient with leptomeningeal involvement, who presented with neurological symptoms as the first clinical sign, and a diagnosis of leptomeningeal was made based on CSF cytology and flow cytometry. Treatment consisted of radiation therapy and intrathecal chemotherapy with arabinoside-cytosine and systemic chemotherapy. On the basis of this patient-report together with 37 other previously reported cases, the clinical characteristics together with treatment options and outcome of leptomeningeal involvement in CLL are reviewed. Our case together with data from the literature indicate that a timely diagnosis and intensive treatment of leptomeningeal disease of CLL may lead to longstanding and complete resolution of neurological symptoms.
Assuntos
Leucemia Linfocítica Crônica de Células B/patologia , Infiltração Leucêmica/patologia , Meninges/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Diagnóstico Diferencial , Evolução Fatal , Feminino , Transtornos Neurológicos da Marcha/etiologia , Humanos , Achados Incidentais , Perna (Membro)/inervação , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Infiltração Leucêmica/tratamento farmacológico , Contagem de Leucócitos , Vértebras Lombares/patologia , Linfonodos/patologia , Doenças Linfáticas/patologia , Pessoa de Meia-Idade , Exame Neurológico , Parestesia/etiologia , Reflexo Anormal/fisiologia , Medula Espinal/patologiaRESUMO
An 80-year-old man with von Willebrand's disease was admitted with severe melaena. Despite suppletion with von Willebrand concentrate he continued to be dependent on blood transfusions. Endoscopic examination did not show a bleeding focus. Video capsule endoscopy showed active bleeding from angiodysplasias in the proximal section of the small intestine. Ultimately, treatment with thalidomide was initiated at a dose of 100 mg/day. Soon after starting treatment his stools became normal and his haemoglobin level stabilised. No bleeding problems occurred for 11 months, after which the thalidomide treatment was stopped because of the potential side effects. Two months later he again developed melaena and treatment with thalidomide was restarted with a successful outcome. Trying to lower the dose to 50 mg resulted in rebleeding after three months with stabilisation after increasing the dose to 100 mg again. Monotherapy with thalidomide improves the clinical picture but may not be sufficient in the long term. Additional therapy, such as argon plasma coagulation or the use of the novel drug lenalidomide, might be necessary.
Assuntos
Angiodisplasia/tratamento farmacológico , Gastroenteropatias/tratamento farmacológico , Talidomida/administração & dosagem , Idoso de 80 Anos ou mais , Angiodisplasia/complicações , Gastroenteropatias/complicações , Hemorragia Gastrointestinal/tratamento farmacológico , Hemorragia Gastrointestinal/etiologia , Humanos , Lenalidomida , Masculino , Melena/tratamento farmacológico , Melena/etiologia , Recidiva , Talidomida/análogos & derivados , Resultado do Tratamento , Doenças de von Willebrand/complicaçõesRESUMO
OBJECTIVE: To study whether stopping elastic compression stockings (ECS) after 12 months is non-inferior to continuing them for 24 months after proximal deep venous thrombosis. DESIGN: Multicentre single blind non-inferiority randomised controlled trial. SETTING: Outpatient clinics in eight teaching hospitals in the Netherlands, including one university medical centre. PARTICIPANTS: Patients compliant with compression therapy for 12 months after symptomatic, ultrasound proven proximal deep venous thrombosis of the leg. INTERVENTIONS: Continuation or cessation of ECS 12 months after deep venous thrombosis. MAIN OUTCOME MEASURES: The primary outcome was the incidence of post-thrombotic syndrome 24 months after diagnosis of deep venous thrombosis, as assessed by the standardised Villalta scale in an intention to treat analysis. The predefined non-inferiority margin was 10%. The main secondary outcome was quality of life (VEINES-QOL/Sym). RESULTS: 518 patients compliant with ECS and free of post-thrombotic syndrome were randomised one year after diagnosis of deep venous thrombosis to stop or continue ECS therapy for another year. In the stop-ECS group, 51 of 256 patients developed post-thrombotic syndrome, with an incidence of 19.9% (95% confidence interval 16% to 24%). In the continue-ECS group, 34 of 262 patients developed post-thrombotic syndrome (incidence 13.0%, 9.9% to 17%), of whom 85% used ECS six or seven days a week during the study period, for an absolute difference of 6.9% (95% confidence interval upper limit 12.3%). Because the upper limit of the 95% confidence interval exceeds the predefined margin of 10%, non-inferiority was not reached. The number needed to treat to prevent one case of post-thrombotic syndrome by continuing ECS was 14 (95% confidence interval lower limit 8). Quality of life did not differ between the two groups. CONCLUSION: Stopping ECS after one year in compliant patients with proximal deep venous thrombosis seemed not to be non-inferior to continuing ECS therapy for two years in this non-inferiority trial. TRIAL REGISTRATION: Netherlands Trial Register NTR1442.
Assuntos
Tratamento Conservador , Extremidade Inferior/irrigação sanguínea , Síndrome Pós-Trombótica , Meias de Compressão , Veias , Trombose Venosa , Adulto , Idoso , Tratamento Conservador/instrumentação , Tratamento Conservador/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Processos e Resultados em Cuidados de Saúde , Síndrome Pós-Trombótica/diagnóstico , Síndrome Pós-Trombótica/etiologia , Síndrome Pós-Trombótica/fisiopatologia , Síndrome Pós-Trombótica/prevenção & controle , Prevenção Terciária/instrumentação , Prevenção Terciária/métodos , Fatores de Tempo , Ultrassonografia/métodos , Veias/diagnóstico por imagem , Veias/fisiopatologia , Trombose Venosa/complicações , Trombose Venosa/diagnóstico , Trombose Venosa/fisiopatologia , Trombose Venosa/terapiaRESUMO
OBJECTIVE: Previously, we observed an increased recognition of malignant cells by cytotoxic T lymphocytes (CTL) when the target cells were cultured in vitro for 24 hours. In this study, we analyzed the expression of costimulatory and adhesion molecules on acute myeloid leukemia (AML) cells and determined whether 24-hour culture of the cells was associated with upregulation of these molecules. We analyzed whether this incubation period improved recognition of AML cells by CTL. MATERIALS AND METHODS: Expression of costimulatory and adhesion molecules on leukemic blasts of 34 patients comprising each AML FAB subclassification were analyzed directly and after 24 hours of culture, and the recognition of these AML cells by an HLA-A2 restricted CTL clone was determined. Blocking studies were performed with antibodies against CD54, CD58, and CD11a. RESULTS: Immunophenotyping showed a low expression of CD80 and CD40 and a variable CD86 expression on most AML cells. CD54 expression was generally low, CD58 expression was high, and CD11a expression was variable, with a higher expression in AML M0, M1, M4, and M5. Twenty-four hours of culture resulted in a significant upregulation of CD40, CD54, and CD58. Impaired recognition of AML cells by the HLA-A2 restricted CTL clone was enhanced 100-200% by 24 hours of preincubation of the leukemic cells. Blocking studies showed the importance of multiple adhesion molecules on the AML cells. CONCLUSION: Low expression of multiple costimulatory and adhesion molecules on AML could be upregulated by 24 hours of culture, which was associated with increased recognition of the AML blasts by CTL. Blocking multiple adhesion molecules completely abolished CTL recognition, showing the importance of the combination of these molecules for T-cell interaction with AML.
Assuntos
Antígenos CD/imunologia , Antígenos de Neoplasias/imunologia , Moléculas de Adesão Celular/imunologia , Citotoxicidade Imunológica , Imunoterapia Adotiva , Leucemia Mieloide/imunologia , Doença Aguda , Antígenos CD/biossíntese , Antígenos de Neoplasias/biossíntese , Moléculas de Adesão Celular/biossíntese , Citometria de Fluxo , Humanos , Imunofenotipagem , Leucemia Mieloide/terapia , Células Tumorais CultivadasRESUMO
OBJECTIVES: To define the cumulative risk of central nervous system (CNS) relapse in systemic non-Hodgkin lymphoma (NHL); to assess the risk factors of age, sex, malignancy grade, stage, localization, and response to initial therapy; and to evaluate the effect of CNS prophylaxis. PATIENTS AND METHODS: An unselected group of 532 patients with systemic NHL. A retrospective analysis. RESULTS: Eleven patients presented with systemic as well as CNS localization, whereas in 55 patients, CNS relapse occurred later. The cumulative risk of CNS relapse at 4 years for all 532 patients was 19%. High-grade NHL carried a 39% risk of CNS relapse, with the vast majority of relapses occurring in the first 14 months after the initial diagnosis. The cumulative risk in patients with intermediate-grade NHL was considerable (22%) and dispersed throughout a much longer period (6 years). Patients with low-grade NHL still carried a 7% risk of CNS relapse; in all these patients, low malignancy grade was transformed into a higher malignancy grade at that time. In a multivariate analysis, high- and intermediate-grade NHL and advanced stage were independent risk factors for CNS relapse. There was not any strong evidence for a beneficial role of CNS prophylaxis in patients with intermediate- and high-grade NHL, but a retrospective analysis cannot be conclusive with regard to the effect of therapy. Systemic relapse occurred rapidly after CNS relapse, resulting in a median survival time after CNS relapse of only 2 months. CONCLUSIONS: Patients with high- and intermediate-grade NHL carry a considerable risk of CNS relapse. Advanced stage is an additional independent risk factor. The role of CNS prophylaxis seems to be disappointing, but a retrospective analysis cannot be conclusive. Prognosis after CNS relapse is poor.
Assuntos
Doenças do Sistema Nervoso Central/etiologia , Linfoma não Hodgkin/complicações , Adolescente , Adulto , Fatores Etários , Idoso , Doenças do Sistema Nervoso Central/prevenção & controle , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Linfoma não Hodgkin/patologia , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Fatores de Risco , Fatores SexuaisRESUMO
To increase the immunogenicity of leukemic cells, attempts were made to generate dendritic-like antigen presenting cells (DC) from AML blasts from 14 patients with AML FAB classifications M0-M5. Leukemic cells were cultured in the presence or absence of various cytokines including GM-CSF, SCF, TNF-alpha, IL-4, and gamma-interferon. After various intervals recovery of viable cells was measured and expression of CD80, CD86, CD40, CD54, CD58, and CD11a was analyzed by flow cytometry. Functionally, DC derived from six AML samples were tested in a mixed lymphocyte response (MLR) using HLA-DR mismatched donor T cells as responder cells. Proliferation (5/14) or increased survival (7/14) of AML cells was observed in the presence of GM-CSF, SCF, and TNF-alpha. Only in the AML M2, M3, and M4 FAB subtypes proliferation was found. GM-CSF, SCF, and TNF-alpha induced morphologic changes typical for DC and increased the expression of costimulatory and adhesion molecules. No significant effect of IL-4 or gamma-interferon was observed. The day of maximal expression of these molecules varied. In cases with minor upregulation of CD80 or CD86, no further stimulation using CD40-L activation was observed. In the three cases tested, the DC-like cells retained the chromosomal abnormalities present in the original AML cells. In five out of six cases tested an increase in allostimulatory capacity was found at the day of maximal expression of costimulatory and adhesion molecules. In two patients a decrease in stimulatory capacity was found at day 7 compared with day 2 correlating with a decreased expression of these molecules. In conclusion, AML cells can be induced to increase their stimulatory capacity by upregulating costimulatory and adhesion molecules.
Assuntos
Células Dendríticas/imunologia , Leucemia Mieloide/imunologia , Doença Aguda , Adulto , Idoso , Antígenos CD/análise , Antígeno B7-1/análise , Antígeno B7-2 , Antígenos CD40/análise , Antígenos CD40/farmacologia , Contagem de Células , Técnicas de Cocultura , Análise Citogenética , Citocinas/farmacologia , Células Dendríticas/efeitos dos fármacos , Feminino , Citometria de Fluxo , Humanos , Imunização , Masculino , Glicoproteínas de Membrana/análise , Pessoa de Meia-Idade , Células Tumorais CultivadasRESUMO
We report the results of a retrospective single-center study comparing engraftment, acute and chronic GVHD, relapse and survival in patients with malignant hematological disorders transplanted with allogeneic peripheral blood stem cells (alloPBSCT, n = 40) or bone marrow cells (alloBMT, n = 42). All transplants were T cell depleted by in vitro incubation with the Campath-1 monoclonal antibody. Primary graft failure occurred in none of the patients receiving an alloPBSCT compared with 3/42 of the recipients of an alloBMT. In addition, two patients in the alloBMT group showed no platelet engraftment. Recipients of PBSC had a more rapid recovery of neutrophils (median 14 days) compared to BM transplant recipients (median 32 days). Platelet recovery was also accelerated in PBSC recipients compared to BM recipients (11 vs 38 days). There was an increase in the incidence of grade II acute GVHD and chronic GVHD in patients after alloPBSCT (18% and 23%, respectively) compared to patients receiving alloBMT (5% and 8%, respectively). The 2-year cumulative incidence of relapse was similar in both groups (47%). At 6 months after transplantation, transplant-related mortality (TRM) was lower in PBSCT recipients than in BMT recipients. However, at a follow-up of 3 years TRM was similar in both groups. The disease-free survival rate at 3 years after transplantation did not differ between the groups (42% for PBSCT and 41% for BMT recipients). Our results indicate that T cell-depleted alloPBSCT compared to alloBMT is associated with a more rapid hematopoietic reconstitution and a decreased TRM at 6 months follow-up after transplantation. However, at a follow-up of 3 years, no sustained survival benefits were observed.
Assuntos
Transplante de Medula Óssea/normas , Transplante de Células-Tronco Hematopoéticas/normas , Linfócitos T/imunologia , Adulto , Células Sanguíneas/transplante , Transplante de Medula Óssea/mortalidade , Feminino , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Depleção Linfocítica , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de Tempo , Transplante Homólogo , Resultado do TratamentoRESUMO
Two patients are described with a mycotic aneurysm caused by streptococcus pneumoniae infection. The patients presented with back pain and fever, and had an antecedent history of lower respiratory tract infection; neither of them were suffering from endocarditis. Mycotic aneurysms are a rare disorder with, over the years, a changing spectrum of presentation, localisation and bacterial aetiology. S. pneumoniae infection has only very rarely been reported as a cause of mycotic aneurysms. Since 1986, 14 patients with a mycotic aneurysm were treated at the Leiden University Hospital. Of these patients, 5 had mycotic aneurysms caused by S. pneumoniae infection. The mortality in these patients was high. In this communication, we would like to draw attention to S. pneumoniae infections as an emerging cause of mycotic aneurysms.
Assuntos
Aneurisma Infectado/microbiologia , Aneurisma da Aorta Abdominal/microbiologia , Infecções Pneumocócicas/diagnóstico , Streptococcus pneumoniae/isolamento & purificação , Idoso , Aneurisma Infectado/diagnóstico , Aneurisma Infectado/terapia , Antibacterianos/uso terapêutico , Aorta Abdominal/microbiologia , Aneurisma da Aorta Abdominal/diagnóstico , Aneurisma da Aorta Abdominal/terapia , Terapia Combinada , Intervalo Livre de Doença , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Infecções Pneumocócicas/terapia , Escarro/microbiologiaRESUMO
We describe four patients with a mature T-cell disorder. These four specific entities belong to a group formerly called "T-cell chronic lymphocytic leukaemia" (T-CLL). Nowadays we understand that these chronic T-cell lymphoproliferative disorders consist of four different entities. They stand out as well-described and separate disorders on the basis of their clinical, immunophenotypic and cytogenetic properties. Unfortunately, the majority of patients have a bad response to chemotherapy. The purine analogs may offer a better prognosis for some patients.
Assuntos
Leucemia de Células T , Transtornos Linfoproliferativos , Micose Fungoide , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Humanos , Leucemia de Células T/complicações , Leucemia de Células T/diagnóstico , Leucemia de Células T/tratamento farmacológico , Transtornos Linfoproliferativos/complicações , Transtornos Linfoproliferativos/diagnóstico , Transtornos Linfoproliferativos/tratamento farmacológico , Masculino , Micose Fungoide/complicações , Micose Fungoide/diagnóstico , Micose Fungoide/tratamento farmacológico , Prognóstico , Purinas/uso terapêutico , Síndrome de SézaryRESUMO
A patient is described who presented with the clinical picture of respiratory failure, persistent comatose state and myocardial injury after being struck by lightning. The discussion reviews the management of lightning injuries with emphasis on cardiovascular and neurological complications.
Assuntos
Coma/etiologia , Lesões Provocadas por Raio/complicações , Infarto do Miocárdio/etiologia , Insuficiência Respiratória/etiologia , Adulto , Coma/fisiopatologia , Evolução Fatal , Humanos , Lesões Provocadas por Raio/fisiopatologia , Masculino , Infarto do Miocárdio/fisiopatologia , Insuficiência Respiratória/fisiopatologia , RessuscitaçãoRESUMO
A 74-year-old man developed a severe bleeding disorder on the basis of acquired Factor VIII (F VIII) inhibitor. Coagulation assays showed a prolonged activated partial thromboplastin time (APTT) with a normal prothrombin time (PT);F VIII level was 0.07 IU and F VIII inhibitor level 8.8 Bethesda units (BU). At least half the cases of acquired haemophilia A are associated with pregnancy, the postpartum period or an underlying malignancy or autoimmune disease. Haemorrhagic diathesis can be severe and life-threatening. Treatment of acute haemorrhages consists of human or porcine factor VIII concentrate, activated prothrombin complex concentrate (FEIBA) or recombinant factor VIIa, depending on the antibody titre. Immunosuppressive therapy is successful in at least 60% of the patients in making the inhibitor disappear. In patients with a spontaneous haemorrhagic diathesis, a thorough medical history should be taken, coagulation assays should be performed and a specialist should be consulted.
Assuntos
Fator VIII/antagonistas & inibidores , Hemofilia A/etiologia , Idoso , Hemofilia A/diagnóstico , Humanos , Masculino , Tempo de Tromboplastina ParcialRESUMO
Cysticercosis of the CNS, caused by the pork tapeworm Taenia solium, was diagnosed on the basis of serological and imaging examination in two patients, a woman aged 50 and a man aged 40 years. The former patient suffered from aphasia, headache and epileptic attacks, the latter mostly from epilepsy. Cysticercosis of the CNS occurs mainly in the tropics but is occasionally observed in the Netherlands in people who have been to the tropics, such as the patients reported. Both ultimately recovered after drug therapy which included praziquantel.
Assuntos
Encefalopatias/diagnóstico , Cisticercose/diagnóstico , Adulto , Anti-Helmínticos/uso terapêutico , Neoplasias Encefálicas/diagnóstico , Cisticercose/tratamento farmacológico , Diagnóstico Diferencial , Epilepsia/etiologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Praziquantel/uso terapêuticoRESUMO
A 16-year-old woman presented with anaemia, jaundice, vomiting and nosebleed. She had acute hepatic failure and haemolytic anaemia and developed acute respiratory distress syndrome (ARDS). Wilson's disease was diagnosed. After the ARDS resolved the patient underwent a successful orthotopic liver transplantation. Diagnostic combinations for Wilson's disease are ceruloplasmin < 0.2 g/l with Kayser-Fleischer rings, liver copper > 250 micrograms/g (dry weight) with Kayser-Fleischer rings, or homozygosity for a Wilson mutation on the 13th chromosome. In acute liver failure a copper excretion in 24 h-urine above 1 mg is diagnostic for Wilson's disease, while an elevated serum copper concentration makes this diagnosis very likely. Therapeutic options for Wilson's disease are chelation therapy and liver transplantation; in most cases of acute liver failure due to Wilson's disease orthotopic liver transplantation (preceded by albumin dialysis) is indicated. Nazer's index should be used in addition to the regular King's College criteria for liver transplantation indication.
Assuntos
Anemia Hemolítica/etiologia , Transtornos da Coagulação Sanguínea/etiologia , Degeneração Hepatolenticular/complicações , Degeneração Hepatolenticular/diagnóstico , Falência Hepática Aguda/etiologia , Síndrome do Desconforto Respiratório/etiologia , Adolescente , Diagnóstico Diferencial , Feminino , Degeneração Hepatolenticular/patologia , Degeneração Hepatolenticular/cirurgia , Humanos , Transplante de Fígado , Países Baixos , Guias de Prática Clínica como AssuntoRESUMO
Systemic mastocytosis may be accompanied by a second haematological malignancy, usually of myeloid origin. However, a number of case reports describe systemic mastocytosis coexisting with a second haematological malignancy of lymphoid origin. Here, we report a case of a 74-year-old man with systemic mastocytosis who developed a diffuse large B-cell lymphoma. A short overview of the literature concerning mastocytosis accompanied by a second haematological malignancy is presented.
Assuntos
Linfoma Difuso de Grandes Células B/complicações , Mastocitose Sistêmica/complicações , Idoso , Anticorpos Monoclonais Murinos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Evolução Fatal , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Masculino , Mastocitose Sistêmica/tratamento farmacológico , Prednisolona/administração & dosagem , RituximabRESUMO
We describe a case of haemophagocytic syndrome caused by Histoplasma capsulatum reactivation in a patient with chronic lymphocytic leukaemia treated with fludarabine and alemtuzumab. He presented with fever, pancytopenia, increased serum ferritin, lactate dehydrogenase and soluble interleukin-2 receptor. A bone marrow aspirate showed haemophagocytosis and possibly a yeast infection. Treatment with cyclosporine, dexamethasone, etoposide and caspofungin was started. After initial improvement his condition deteriorated. A second bone marrow examination confirmed a Histoplasma infection. After treatment with amphotericin B, the fever resolved and blood counts normalised. Haemophagocytic syndrome is a critical condition with high mortality that requires immunosuppressive therapy. The underlying cause should be investigated and treated. In this case a Histoplasma reactivation is described in a severely immunocompromised host years after the patient had left the endemic area.
Assuntos
Antibacterianos/uso terapêutico , Histoplasmose/complicações , Hospedeiro Imunocomprometido , Leucemia Linfocítica Crônica de Células B/imunologia , Linfo-Histiocitose Hemofagocítica/etiologia , Histoplasmose/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
The expression of adhesion and co-stimulatory molecules, and chemokine and death receptors such as tumour necrosis factor (TNF) and FAS on acute myeloid leukaemia (AML) may influence the biology of the disease and response to chemotherapy and immunotherapy. In this study, we analysed the expression of these molecules in 99 AML patients using monoclonal antibodies and flow cytometry, and correlated the expression with French-American-British (FAB) classification and survival. The following molecules were studied: the co-stimulatory molecules CD80, CD86 and CD40; the adhesion molecules CD11a-c, CD31, CD43, CD50, CD54, CD102, CD58 and CD62L; the chemokine receptor CXCR4; and the death receptors TNFR1 and TNFR2 and FAS. The expression of all molecules was significantly higher in the M4/M5 FAB subgroups except for CD80, CD43, CD54 and CD62L. The AML M3 subgroup had a significant lower expression of CD11a (P = 0.02) and CD11c (P = 0.03). Five-year survival was significantly shorter in cases of high CD40 expression [> 20% positive cells, relative risk (RR) 2.56, P = 0.02] or high CD11a expression (> 80% positive cells, RR 2.6, P = 0.03). This effect was most prominently present in the AML M4/M5 FAB subgroups. We conclude that the expression levels of adhesion and co-stimulatory molecules, CXCR4 and apoptosis-receptors are predominantly FAB subtype-related with high CD40 and CD11a expression as poor prognostic factors.
Assuntos
Antígenos CD/metabolismo , Antígenos de Neoplasias/metabolismo , Biomarcadores Tumorais/metabolismo , Moléculas de Adesão Celular/metabolismo , Leucemia Mieloide/metabolismo , Doença Aguda , Adolescente , Adulto , Idoso , Antígenos CD40/metabolismo , Feminino , Humanos , Antígeno-1 Associado à Função Linfocitária/metabolismo , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Receptores CXCR4/metabolismo , Receptores do Fator de Necrose Tumoral/metabolismo , Taxa de Sobrevida , Receptor fas/metabolismoRESUMO
We evaluated the efficacy of recombinant human interleukin-3 (rhIL-3) in reducing the number of platelet transfusions and major infections after autologous bone marrow transplantation (ABMT) in patients with malignant lymphoma. 198 patients with non-Hodgkin's lymphoma (NHL, n = 111) and Hodgkin's disease (HD, n = 87) were randomized to receive rhIL-3 10 microgram/kg/d (n = 130) or placebo (n = 68) for a maximum of 28 d after ABMT. Several well-known conditioning regimens were used. From day 1 after ABMT patients were treated with placebo or rhIL-3 at a dose of 10 microgram/kg/d by continuous i.v. infusion for 7 d and then by s.c. administration for 21 d or until platelet (50 x 109/l) and neutrophil (0.5 x 109/l) recovery had occurred. Treatment was completed in 54% of the patients in the rhIL-3 group versus 75% in the placebo group (P < 0.004). Adverse events were the main reason for premature discontinuation in the IL-3 group (23% IL-3 v 5% placebo). The median number of platelet transfusions was not significantly different between the IL-3 group and the placebo group (8.0 IL-3 v 6.0 placebo, P = 0.09). Platelet engraftment (>/= 20 x 109/l) was not significantly faster in the IL-3 group (28 d in the IL-3 and 27 d in the placebo group, P = 0.06) and the incidence of haemorrhagic complications was similar in both groups. In patients receiving the full intended dose of rhIL-3, platelet engraftment to >/= 20 x 109/l was delayed (P = 0.007). The median time to neutrophil engraftment was 23 d in the IL-3 and 25 d for the placebo group (P = 0.39). There was no difference in the incidence of major infections. We conclude that treatment with IL-3 has no clinical benefit in patients receiving ABMT for malignant lymphoma.