RESUMO
The spontaneous formation of colony-forming units granulocyte/macrophage (CFU-GM) in semisolid cultures has been shown to be due to the endogenous release of cytokines and/or to the hypersensitivity of cells against growth factors. We have reported that increased autonomous CFU-GM growth is an in vitro characteristic of myelofibrosis (MF) which may reflect aberrant hematopoiesis in vivo. Because of its cytokine synthesis-inhibiting action, we speculated that interleukin-10 (IL-10) may inhibit pathological overproduction of myeloid cells in MF by suppression of autonomous myelopoiesis. In this study, IL-10 significantly inhibited autonomous CFU-GM formation in vitro from peripheral blood mononuclear cells (PB MNC) in 10 of 11 patients with MF tested. In all patients, there was a mean inhibition of 69% ranging from 35% to 100%. Suppression of autonomous CFU-GM formation by IL-10 was dose dependent and reversible by the addition of anti-IL-10 antibodies. Our results indicate that IL-10 is a potentially useful molecule to affect aberrant myelopoiesis in patients with MF.
Assuntos
Interleucina-10/metabolismo , Mielopoese , Mielofibrose Primária/metabolismo , Idoso , Idoso de 80 Anos ou mais , Ensaio de Unidades Formadoras de Colônias , Relação Dose-Resposta a Droga , Feminino , Células Progenitoras de Granulócitos e Macrófagos/efeitos dos fármacos , Células Progenitoras de Granulócitos e Macrófagos/metabolismo , Humanos , Interleucina-10/farmacologia , Masculino , Pessoa de Meia-IdadeRESUMO
Bleeding and thrombosis are important complications in patients with malignant lymphomas. They may be due to direct actions of the lymphoma, such as venous compression or bone marrow infiltration, but they may also be caused by paraneoplastic phenomena, which are immune-mediated in most of the cases. The most important paraneoplastic immune-mediated disorders in lymphomas causing bleeding are autoimmune thrombocytopenia, acquired hemophilia A and acquired von Willebrand syndrome. In addition, there are a variety of other less common immune-mediated bleeding conditions, such as acquired thrombasthenia, acquired factor X-, V-, XI-, XII-, or prothrombin deficiency. The presence of antiphospholipid antibodies is a rare condition predisposing to venous and arterial thrombosis and there are other very uncommon conditions, which predispose exclusively to arterial thrombosis such as hyperlipidemic xanthomatosis. Interestingly, there is hardly any correlation between the histological type and the aggressiveness of lymphoma and the type and prevalence of the immune-mediated conditions. Successful treatment of the underlying lymphoma is often associated with definite and sustained resolution of the immune-mediated disorder.
Assuntos
Hemorragia/imunologia , Linfoma/imunologia , Trombose/imunologia , Humanos , Linfoma/sangue , Trombose/sangueRESUMO
Autoimmune hemolytic anemia is a heterogeneous disease with respect to the type of the antibody involved and the absence or presence of an underlying condition. Treatment decisions should be based on careful diagnostic evaluation. Primary warm antibody autoimmune hemolytic anemias respond well to steroids, but most patients remain steroid-dependent, and many require second-line treatment. Currently, splenectomy can be regarded as the most effective and best-evaluated second-line therapy, but there are still only limited data on long-term efficacy and adverse effects. The monoclonal anti-CD20 antibody rituximab is another second-line therapy with documented short-term efficacy, but there is limited information on long-term efficacy and side effects. The efficacy of immunosuppressants is poorly evaluated. Primary cold antibody autoimmune hemolytic anemias respond well to rituximab but are resistant to steroids and splenectomy. The most common causes of secondary autoimmune hemolytic anemias are malignancies, immune diseases, or drugs. They may be treated in a way similar to primary autoimmune hemolytic anemias, by immunosuppressants or by treatment of the underlying disease.
Assuntos
Algoritmos , Anemia Hemolítica Autoimune/diagnóstico , Anemia Hemolítica Autoimune/terapia , Adulto , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Murinos , Humanos , Fatores Imunológicos/uso terapêutico , Guias de Prática Clínica como Assunto , Rituximab , EsplenectomiaRESUMO
Although imatinib has become standard first-line therapy in chronic myelogenous leukemia (CML), allogeneic hematopoietic stem cell transplantation (HSCT) is still considered to be an important treatment alternative for patients with drug resistance or advanced disease. We retrospectively analyzed 175 adult CML patients who underwent HSCT at our institution between 1983 and 2007, with the aim to compare outcomes in patient subgroups and to identify prognostic variables. The median follow-up was 65 months. The probability of overall survival (OS) for all patients was 62%, with a significant improvement seen in the imatinib-era (2001-2007) compared to previous time periods (P <.05). Furthermore, a significantly better outcome for patients with chronic phase CML compared to patients with accelerated or blast phase could be observed (P < .05). Cumulative incidence (CI) of treatment-related mortality (TRM) was 9.7% at 100 days and 1 year after HSCT. CI of relapse was 5% at 1 year and 7.5% at 3 years after HSCT. Post-HSCT outcome was not influenced by pretreatment therapy with imatinib, donor type, or a conditioning regimen with total body irradiation (TBI). These data confirm earlier observations and suggest that allogeneic HSCT is still an important treatment option for high-risk patients with CML, and should thus remain an integral component in current and future treatment algorithms.
Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas/tendências , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Adulto , Benzamidas , Feminino , Seguimentos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Mesilato de Imatinib , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Masculino , Pessoa de Meia-Idade , Piperazinas/uso terapêutico , Prognóstico , Pirimidinas/uso terapêutico , Recidiva , Estudos Retrospectivos , Taxa de Sobrevida , Condicionamento Pré-Transplante/métodos , Transplante Homólogo , Resultado do Tratamento , Adulto JovemRESUMO
Diagnosis and management of immune thrombocytopenic purpura (ITP) remain largely dependent on clinical expertise and observations more than on evidence derived from clinical trials of high scientific quality. One major obstacle to the implementation of such studies and in producing reliable meta-analyses of existing data is a lack of consensus on standardized critical definitions, outcome criteria, and terminology. Moreover, the demand for comparative clinical trials has dramatically increased since the introduction of new classes of therapeutic agents, such as thrombopoietin receptor agonists, and innovative treatment modalities, such as anti-CD 20 antibodies. To overcome the present heterogeneity, an International Working Group of recognized expert clinicians convened a 2-day structured meeting (the Vicenza Consensus Conference) to define standard terminology and definitions for primary ITP and its different phases and criteria for the grading of severity, and clinically meaningful outcomes and response. These consensus criteria and definitions could be used by investigational clinical trials or cohort studies. Adoption of these recommendations would serve to improve communication among investigators, to enhance comparability among clinical trials, to facilitate meta-analyses and development of therapeutic guidelines, and to provide a standardized framework for regulatory agencies.
Assuntos
Púrpura Trombocitopênica Idiopática/classificação , Púrpura Trombocitopênica Idiopática/diagnóstico , Púrpura Trombocitopênica Idiopática/terapia , Terminologia como Assunto , Diretrizes para o Planejamento em Saúde , Humanos , Cooperação Internacional , Padrões de Referência , Resultado do TratamentoRESUMO
Patients undergoing splenectomy have an increased risk of splenic/portal vein thrombosis. We used several databases to identify publications dealing with this risk and analyzed incidence, risk factors and outcome. The risk of splenic portal vein thrombosis has been addressed in prospective and retrospective randomized or non-randomized studies. All studies combined, the overall risk is 3.3%. Risk factors are big spleens (i.e. myeloproliferative disorders) and hereditary hemolytic anemias, whereas the risk is low in autoimmune thrombocytopenia and trauma. The incidence is approximately the same in laparoscopic and open splenectomy. The median time from splenectomy to symptomatic splenic vein thrombosis is 8-12 days. Postoperative antithrombotic prophylaxis ranged from no prophylaxis to heparin for seven days or longer. Treatment of symptomatic splenic vein thrombosis with heparin and warfarin leads to complete resolution of thrombosis in 67%, to partial resolution in 13%, but persistent occlusion, portal hypertension or cavernoma occurred in 20%.The long-term outcome of treatment failures is unknown. Well-designed randomized studies on the prophylaxis of venous thromboembolism after splenectomy are urgently needed.
Assuntos
Veia Porta , Complicações Pós-Operatórias/prevenção & controle , Esplenectomia/efeitos adversos , Veia Esplênica , Trombose Venosa/etiologia , Trombose Venosa/prevenção & controle , Adulto , Humanos , Incidência , Laparoscopia/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Trombose Venosa/epidemiologiaRESUMO
Autoimmune thrombocytopenia is a common immunehematologic complication in non-Hodgkin's lymphomas and may complicate the treatment. We analyzed an original series from our institute as well as published cases of non-Hodgkin's lymphomas (excluding chronic lymphocytic leukemia) associated with autoimmune thrombocytopenia with regard to demographic factors, prevalence in non-Hodgkin's lymphoma subtypes and treatment outcome. The male/female ratio is 1.75. Half of the cases occurred prior to diagnosis of lymphoma. Chemotherapy is the best treatment in many non-Hodgkin's lymphomas patients with autoimmune thrombocytopenia compared with standard treatment of autoimmune thrombocytopenia. Splenectomy is effective in splenic marginal zone lymphoma. Autoimmune thrombocytopenia in patients with non-Hodgkin's lymphomas is potentially life-threatening and difficult to treat.
Assuntos
Linfoma não Hodgkin/epidemiologia , Púrpura Trombocitopênica Idiopática/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Criança , Terapia Combinada , Comorbidade , Feminino , Humanos , Leucemia de Células Pilosas/tratamento farmacológico , Leucemia de Células Pilosas/epidemiologia , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/imunologia , Linfoma não Hodgkin/cirurgia , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/epidemiologia , Transplante de Células-Tronco de Sangue Periférico , Complicações Pós-Operatórias/epidemiologia , Prevalência , Esplenectomia , Resultado do Tratamento , Macroglobulinemia de Waldenstrom/epidemiologiaRESUMO
Autoimmune haemolytic anaemia (AIHA) is an immune disorder caused by antibodies directed against unmodified autologous red cells. The disorder may be a primary (idiopathic) or a secondary disease. The diagnosis is based on the presence of anaemia, signs of haemolysis with reticulocytosis, low haptoglobin, increased lactate dehydrogenase, elevated indirect bilirubin, and a positive direct antiglobulin test (Coombs test). Sometimes, not all of these typical features are present. Most AIHA are caused by warm antibodies, whereas cold antibodies are less commonly detected. While half of the warm antibody-based AIHA are idiopathic anaemias, almost all cold antibody AIHA are secondary anaemias. Underlying diseases are Non Hodgkin's lymphomas and systemic autoimmune disorders, and less frequently organ transplantation, infections, or solid tumors. Moreover, AIHA is an important complication of treatment with nucleoside analogs. Most patients with AIHA require therapy. In warm antibody AIHA, standard first line therapy are glucocorticosteroids with or without high dose immunoglobulins, whereas splenectomy is considered second-line therapy. Response rates of primary AIHA to corticosteroid therapy are high. After initial remission, the dose should be tapered down slowly and with caution, and in some cases, low-dose maintenance therapy is required. The efficacy of standard therapy is low in secondary AIHA that develops in lymphoma patients, posttransplant patients, or tumor patients. Among other immunosuppressive treatments, rituximab (anti-CD20) appears to be highly effective in patients with warm antibody AIHA refractory to standard therapy. Mycophenolate mofetil is quite effective in AIHA patients with an underlying autoimmune or lymphoproliferative disease. Patients with cold agglutinins are refractory to steroids and splenectomy. Half of these patients may respond to rituximab, although responses usually are short-lived. Sometimes, AIHA that is associated with malignant lymphomas or tumors, disappears after successful anti-lymphoma or anti-tumor therapy.
Assuntos
Anemia Hemolítica Autoimune/diagnóstico , Adulto , Algoritmos , Anemia Hemolítica Autoimune/etiologia , Anemia Hemolítica Autoimune/terapia , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Murinos , Autoanticorpos/sangue , Diagnóstico Diferencial , Glucocorticoides/uso terapêutico , Humanos , Imunização Passiva , Prognóstico , Fatores de Risco , Rituximab , EsplenectomiaRESUMO
BACKGROUND: Imatinib, a selective inhibitor of the BCR-ABL tyrosine kinase, produces high response rates in patients with chronic-phase chronic myeloid leukemia (CML) who have had no response to interferon alfa. We compared the efficacy of imatinib with that of interferon alfa combined with low-dose cytarabine in newly diagnosed chronic-phase CML. METHODS: We randomly assigned 1106 patients to receive imatinib (553 patients) or interferon alfa plus low-dose cytarabine (553 patients). Crossover to the alternative group was allowed if stringent criteria defining treatment failure or intolerance were met. Patients were evaluated for hematologic and cytogenetic responses, toxic effects, and rates of progression. RESULTS: After a median follow-up of 19 months, the estimated rate of a major cytogenetic response (0 to 35 percent of cells in metaphase positive for the Philadelphia chromosome) at 18 months was 87.1 percent (95 percent confidence interval, 84.1 to 90.0) in the imatinib group and 34.7 percent (95 percent confidence interval, 29.3 to 40.0) in the group given interferon alfa plus cytarabine (P<0.001). The estimated rates of complete cytogenetic response were 76.2 percent (95 percent confidence interval, 72.5 to 79.9) and 14.5 percent (95 percent confidence interval, 10.5 to 18.5), respectively (P<0.001). At 18 months, the estimated rate of freedom from progression to accelerated-phase or blast-crisis CML was 96.7 percent in the imatinib group and 91.5 percent in the combination-therapy group (P<0.001). Imatinib was better tolerated than combination therapy. CONCLUSIONS: In terms of hematologic and cytogenetic responses, tolerability, and the likelihood of progression to accelerated-phase or blast-crisis CML, imatinib was superior to interferon alfa plus low-dose cytarabine as first-line therapy in newly diagnosed chronic-phase CML.
Assuntos
Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Mieloide de Fase Crônica/tratamento farmacológico , Piperazinas/uso terapêutico , Pirimidinas/uso terapêutico , Adolescente , Adulto , Idoso , Antineoplásicos/administração & dosagem , Benzamidas , Citarabina/administração & dosagem , Progressão da Doença , Feminino , Humanos , Mesilato de Imatinib , Interferon-alfa/administração & dosagem , Leucemia Mieloide de Fase Crônica/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Taxa de SobrevidaRESUMO
BACKGROUND AND OBJECTIVES: Rituximab, a monoclonal chimeric antibody to the CD20 antigen, is an effective therapy for the treatment of non-Hodgkin's lymphomas. Moreover, rituximab has also shown to be effective in various autoimmune diseases including spontaneous antibodies to factor VIII. The aim of this study was to assess the efficacy of rituximab treatment of spontaneous inhibitors to factor VIII. DESIGN AND METHODS: We studied the efficacy of rituximab by analyzing the data of 42 previously published cases as well as one so far unpublished case. For comparison, we also analyzed 44 patients treated with cyclophosphamide/prednisone reported in the literature. RESULTS: Treatment with rituximab resulted in an overall rate of complete remission (CR) of 78.6%. Similar results were found when analyzing patients who had (75%) or had not (77%) received previous treatment with other immunosuppressive drugs. The median time to CR was 8.3 weeks. In follow-up 66% of the patients were still in CR after 2 years and the plateau in the Kaplan-Meier analysis suggests that a substantial number of patients had been cured. Among the 44 patients treated with cyclophosphamide/prednisone reported in the literature, the CR-rate was 84.1%, which was slightly higher than that for rituximab. The median time to CR with cyclophosphamide/prednisone treatment was 6.3 weeks, which was similar to that in the rituximab-treated patients; the probability of continuous CR at 2 years was 94%. INTERPRETATION AND CONCLUSIONS: All in all, both treatment schemes are effective therapies in patients with spontaneous antibodies to factor VIII. Our data analysis is only descriptive and no conclusions can be drawn as to the relative efficacy of the two regimens. However, these data may serve as a useful basis for planning randomized studies to definitively resolve these issues.
Assuntos
Anticorpos Monoclonais/farmacologia , Fator VIII/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Murinos , Antígenos CD20/imunologia , Criança , Ciclofosfamida/uso terapêutico , Fator VIII/química , Feminino , Seguimentos , Humanos , Imunossupressores/farmacologia , Masculino , Pessoa de Meia-Idade , Indução de Remissão , RituximabRESUMO
BACKGROUND AND OBJECTIVES: Few data are available on the long-term risk of recurrence of venous thromboembolism (VTE) and on the impact of established thrombosis risk factors in young women. We aimed to study the recurrence rate and the predictive value of laboratory and clinical thrombosis risk factors in young women. DESIGN AND METHODS: Three-hundred and sixty-one women with a first objectively confirmed VTE under 45 years of age (median age 29.6 years, interquartile range 21.9-36.9) known to our outpatient department were included in this retrospective analysis. These women were re-examined with regard to recurrence of thrombosis and laboratory thrombosis risk factors. RESULTS: Within a median observation period of 11.3 years, recurrent VTE occurred in 141 patients (39.2%). The cumulative probability of recurrence was 10.9% after 2 years, 29% after 10 years and 56% after 20 years. There were no significant associations between recurrence of VTE and laboratory risk factors such as natural inhibitor deficiency, factor V Leiden, the G20210A prothrombin variation, elevated factor VIII or hyperhomocysteinemia. Even women with more than one risk factor were not found to have a higher risk of recurrent VTE. Among the clinical characteristics only an increased body mass index (p=0.03) was associated with a higher probability of recurrence. INTERPRETATION AND CONCLUSIONS: The risk of recurrent VTE in young women is higher than previously expected and remains constant over at least 20 years. Neither clinical features nor laboratory parameters help predict this risk. Thus, also in young women VTE should be regarded as a chronic disease.
Assuntos
Tromboembolia Venosa/complicações , Adolescente , Adulto , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Fatores de Risco , Tromboembolia Venosa/epidemiologiaRESUMO
We analyzed 108 cases of non-CLL non-Hodgkin lymphoma (NHL) associated with autoimmune hemolytic anemia (AIHA) (+/- pure red cell aplasia (PRCA)) or Evans' syndrome. The analysis was based on cases reported in the literature, which were retrieved by means of Pubmed and Medline searches and of an original series of 121 patients with NHL as well as reference lists of papers in the field. The number of cases in various NHL subtypes was small (n = 6-25). Nevertheless, interesting and sometimes unexpected differences in sex prevalence, temporal relationship between onset of lymphoma and AIHA, stage of lymphoma, relative frequency of warm antibody-AIHA (WA-AIHA) and cold antibody (CA-AIHA), association with PRCA and response of AIHA to treatments were noted for various lymphoma entities. WA-AIHA was more frequent in B-cell lymphomas, while CA-AIHA and PRCA predominantly occurred in T-cell lymphomas. Anti-lymphoma treatment seemed to be more effective against AIHA than conventional therapy with steroids or immunoglobulin. Although generated by a literature survey, this compilation of data indicates a complex relation of lymphoma and AIHA and warrants more attention and specific studies.
Assuntos
Anemia Hemolítica Autoimune/etiologia , Linfoma não Hodgkin/complicações , Púrpura Trombocitopênica Idiopática/etiologia , Aplasia Pura de Série Vermelha/etiologia , Anemia Hemolítica Autoimune/diagnóstico , Anemia Hemolítica Autoimune/terapia , Humanos , Leucemia de Células Pilosas/complicações , Leucemia Linfocítica Crônica de Células B/complicações , Linfoma de Células B/complicações , Linfoma Folicular/complicações , Linfoma de Célula do Manto/complicações , Linfoma de Células T Periférico/complicações , Mieloma Múltiplo/complicações , Prognóstico , Fatores de Risco , SíndromeRESUMO
BACKGROUND AND OBJECTIVES: Splenectomy is the most effective treatment for patients with severe autoimmune thrombocytopenia (AITP) who do not have a spontaneous or drug- induced remission. However, this treatment has some short and long term risks. There is no consensus on the indications and optimal timing of splenectomy, since it is unknown up to which time from onset of symptoms a remission can be expected without splenectomy. DESIGN AND METHODS: We studied the incidence of complete or partial remissions in a cohort of 114 adult patients (68 women, 46 men, median age 49.8 years, interquartile range 28.3-68.4) with severe AITP (platelet count < 20x10(9)/L at diagnosis) using Kaplan Meier analysis. Patients who underwent splenectomy during the observation period were censored at the time of splenectomy. RESULTS: The probability of a complete remission was 61% and that of at least a partial remission was 86% at 5 years. The incidence of complete remission was highest within the first 6 months (30%), but increased up to 53% between 6 months and 3 years after diagnosis. The probability of a remission was not related to age, gender, or the presence or absence of platelet antibodies, but was higher in patients with an acute onset of symptoms in comparison to those with an insidious onset (p = 0.0003). The chance of a late remission was higher in patients with an insidious onset of disease. INTERPRETATION AND CONCLUSIONS: These data indicate that splenectomy may be delayed for up to 3 years, in particular in those patients whose AITP has had an insidious onset.
Assuntos
Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Púrpura Trombocitopênica Idiopática/fisiopatologia , Esplenectomia , Corticosteroides/uso terapêutico , Adulto , Análise de Variância , Humanos , Prontuários Médicos , Púrpura Trombocitopênica Idiopática/cirurgia , Recidiva , Estudos Retrospectivos , Esplenectomia/efeitos adversos , Resultado do TratamentoRESUMO
PURPOSE: Recent data suggest that tryptase is produced by blast cells in a group of patients with acute myeloid leukemia (AML). In these patients, serum tryptase levels are elevated at diagnosis and decrease to normal (<15 ng/mL) or near normal values in those achieving complete hematologic remission (CR) after chemotherapy. PATIENTS: In this study, we examined the value of tryptase as a marker of minimal residual AML. In 61 patients with de novo AML exhibiting elevated serum tryptase (>15 ng/mL) at diagnosis, tryptase levels were measured serially during and after chemotherapy by a fluoroenzyme immunoassay. RESULTS: Of the 61 patients, 42 (68.9%) entered hematologic CR in response to induction chemotherapy. Twenty-nine of these 42 patients also entered biochemical remission (BR) defined by a decrease of tryptase levels to normal (<15 ng/mL). The remaining 13 patients exhibited elevated enzyme levels despite of hematologic CR. As assessed by multivariate analysis, the elevated tryptase in CR was found to be an independent prognostic variable concerning disease-free survival. Thus, AML relapses occurred in 15 of 29 patients with CR + BR (52%) and in 12 of 13 patients with CR without BR (92%), resulting in a significantly reduced probability of continuous CR for patients with CR without BR (P < 0.05). In all patients with continuous hematologic CR, tryptase levels remained constantly normal, whereas a recurrent elevation of tryptase in CR was invariably followed by a hematologic relapse. CONCLUSION: A persistently elevated tryptase level in AML in CR is indicative of minimal residual AML and associated with a high risk of relapse.
Assuntos
Leucemia Mieloide/patologia , Neoplasia Residual/patologia , Serina Endopeptidases/sangue , Doença Aguda , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Leucemia Mieloide/tratamento farmacológico , Leucemia Mieloide/enzimologia , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , Recidiva Local de Neoplasia , Neoplasia Residual/enzimologia , Neoplasia Residual/genética , Proteínas de Fusão Oncogênica/genética , Prognóstico , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Risco , Análise de Sobrevida , Fatores de Tempo , TriptasesRESUMO
The incidence of AITP is 20-30/million/year. The diagnosis is based on the finding of an isolated thrombocytopenia without other blood abnormalities and absence of a palpable spleen. Additional tests such as bone marrow examination, determination of platelet antibodies and of thrombopoetin are required only in special cases. The usual first line therapy in patients with bleeding tendency and a low platelet count is prednisolone at a dose of 1 mg/kg/day. Patients who have platelet counts of less than 20,000/microl 3-6 months after steroid therapy are candidates for splenectomy, in particular if more than 0.1 mg/kg/day prednisolone is required to keep the patient free of bleedings. Laparoscopic splenectomy has a low mortality (0.2%) and morbidity (10%). The risk of post-splenectomy overwhelming pneumococcal septicaemia can be minimized by preoperative vaccination. Older patients, who have low platelet counts after splenectomy, have a high bleeding risk. The most effective treatment options for these patients are cyclophosphamide, azathioprine and rituximab, but the choice of treatment should be carefully considered, since the risk of adverse effects may be greater than the risk of fatal bleeding.
Assuntos
Prednisolona/uso terapêutico , Púrpura Trombocitopênica Idiopática/diagnóstico , Púrpura Trombocitopênica Idiopática/terapia , Esplenectomia , Adulto , Anti-Inflamatórios/uso terapêutico , Humanos , Guias de Prática Clínica como Assunto , Padrões de Prática Médica , Púrpura Trombocitopênica Idiopática/epidemiologia , Medição de Risco , Resultado do TratamentoRESUMO
We retrospectively studied the prevalence of C1 esterase inhibitor (C1 INH) deficiency in 131 patients with various lymphomas. We determined C1 INH activity, C1 INH antigen, and C4 concentration at diagnosis and after chemotherapy. In follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL) and chronic lymphocytic leukemia (CLL) consecutive patients were studied. In these entities, the prevalence of C1 INH deficiency was 10.2% in DLBCL, 4.1% in CLL, and 0% in FL and Hodgkin lymphoma. In indolent lymphomas, we identified only single cases of C1 INH deficiency, predominantly in splenic marginal zone lymphomas (SMZL) (four cases). Only three patients were symptomatic while the majority (11 cases) was asymptomatic. In DLBCL patients who were successfully treated with chemotherapy, complete normalization of C1 INH activity and C4 was observed. In contrast, C1 INH deficiency remained in SMZL patients after splenectomy. We conclude that C1 INH deficiency in lymphomas is frequently asymptomatic and responsive to immunochemotherapy.
Assuntos
Angioedemas Hereditários/complicações , Angioedemas Hereditários/epidemiologia , Linfoma/complicações , Linfoma/epidemiologia , Adulto , Idoso , Angioedemas Hereditários/diagnóstico , Angioedemas Hereditários/terapia , Biomarcadores , Terapia Combinada , Complemento C1/imunologia , Proteínas Inativadoras do Complemento 1/genética , Proteínas Inativadoras do Complemento 1/imunologia , Proteínas Inativadoras do Complemento 1/metabolismo , Complemento C4/imunologia , Feminino , Humanos , Imunoterapia , Linfoma/diagnóstico , Linfoma/terapia , Masculino , Pessoa de Meia-Idade , Fenótipo , Prevalência , Esplenectomia , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Primary warm autoimmune hemolytic anemia (WAIHA) is a rare autoimmune disorder frequently responding to corticosteroid first-line treatment and effective second-line treatment options such as splenectomy or anti-CD20 antibody therapy. Disease management is frequently hampered by a lack of evidence. METHODS: We have investigated the probability of sustained treatment-free remission after steroid induction to facilitate clinical decision making regarding timing and necessity of second-line treatments. Response data from 31 patients with primary WAIHA initially treated with steroids were retrospectively analyzed. All patients responded by achieving a hemoglobin of at least 10 mg/dl. RESULTS: After steroid tapering and final withdrawal, 9 of 30 patients remained in unsustained complete remission (CR). The probability of remaining in CR after steroid treatment only was 38.2 % (2 SD 20.6 %) at 15 months. The median remission duration was 100 + months with a range of 12 + to 163 + months. Of note, none of the remaining patients still on steroids achieved CR beyond 15 + months. CONCLUSION: These data indicate that a considerable proportion of patients do not need further treatment and that relapses will not occur after 15 months in CR.
Assuntos
Corticosteroides/administração & dosagem , Anemia Hemolítica Autoimune/tratamento farmacológico , Anemia Hemolítica Autoimune/epidemiologia , Esquema de Medicação , Modelos Estatísticos , Indução de Remissão/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia Hemolítica Autoimune/diagnóstico , Áustria/epidemiologia , Simulação por Computador , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Adulto JovemRESUMO
High dose intermittent ARA-C (2x3 g/m(2) i.v., days 1, 3, 5)=HiDAC was introduced as consolidation in AML by the CALGB-group in 1994. We treated 44 de novo AML patients in CR with up to four cycles of HiDAC (four cycles: 56.8%; three cycles: 22.7%; two cycles: 6.8%; one cycle: 13.7%). Median duration of aplasia (ANC<0.5x10(9)/l) was 12 days. Neutropenic fever occurred in 38.6% of the patients during the first, 52.6% during the second, 45.7% during the third, and in 40% during the fourth cycle. Non-hematologic toxicity was tolerable. The median overall- and disease-free survival were 19.3 and 11.3 months, respectively. The best outcome was seen in patients aged <40 years. These results confirm that HiDAC is a safe and effective consolidation in AML.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Citarabina/uso terapêutico , Daunorrubicina/uso terapêutico , Etoposídeo/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Adolescente , Adulto , Fatores Etários , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Análise de Sobrevida , Resultado do TratamentoRESUMO
The association between malignant disorders and occurrence of venous thromboembolism is well established. Patients with cancer and venous thromboembolism have adverse prognosis. No systematic study on the incidence and prognostic impact of venous thromboembolism in acute leukemia has been performed as yet. We retrospectively evaluated the incidence of symptomatic venous thromboembolism before chemotherapy in 719 patients (371 males and 348 females, median age of 57.4 years), diagnosed with acute leukemia [534 with acute myelogenous leukemia, 185 with acute lymphoblastic leukemia]. Furthermore, the relationship of venous thromboembolism to clinical and laboratory parameters and its impact on prognosis was assessed. Fifteen patients (2.09%) had venous thromboembolism (objectively confirmed in 13 patients) in close temporal relationship to the onset of acute leukemia. The incidence of venous thromboembolism was the same in acute myelogenous and lymphoblastic leukemia. In five patients, pulmonary embolism was documented. Venous thromboembolism occurred in all subtypes of acute leukemia, but was most common in promyelocytic leukemia. All but one patient were treated with anticoagulants. No patient died from treatment-related bleedings or venous thromboembolism. Overall, survival, disease-free survival, and remission duration did not differ between the patient groups with and without venous thromboembolism. In contrast to solid tumors, venous thromboembolism before or at diagnosis of acute leukemia is not associated with poor prognosis.
Assuntos
Leucemia/complicações , Tromboembolia/etiologia , Trombose Venosa/etiologia , Doença Aguda , Anticoagulantes/uso terapêutico , Antineoplásicos/uso terapêutico , Feminino , Humanos , Incidência , Leucemia/epidemiologia , Leucemia/mortalidade , Leucemia Mieloide Aguda/epidemiologia , Leucemia Mieloide Aguda/etiologia , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/etiologia , Prognóstico , Indução de Remissão , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Tromboembolia/epidemiologia , Tromboembolia/mortalidade , Trombose Venosa/epidemiologia , Trombose Venosa/mortalidadeRESUMO
PURPOSE: High-dose intermittent cytarabine is an effective postremission treatment for patients with acute myeloid leukemia (AML). This regimen is a safe approach in patients < 60 years but produced severe neurotoxicity in the elderly. EXPERIMENTAL DESIGN: We have established a dose-reduced age-adapted consolidation using intermediate dose (IDAC; 2 x 1 g/m(2) i.v., days 1, 3, and 5) for AML patients >/= 60 years. Forty-seven de novo AML patients in complete remission (CR; median age, 70 years) were scheduled to receive four consolidation cycles of IDAC. RESULTS: In 25 of 47 patients (53%), all four cycles were administered: 9 (19%) received three cycles; 7 (15%) received two cycles; and 6 patients (12%) one cycle. Treatment was well tolerated without neurotoxicity. The median number of days with severe neutropenia (absolute neutrophil count < 500/microl) was 9. Neutropenic fever occurred in 22 of 47 patients (49%) during the first cycle, in 24 of 41 (60%) during the second, in 15 of 34 (44%) during the third, and in 18 of 25 (72%) during the fourth cycle. Only 1 patient died during consolidation (cardiac failure). The median overall survival, disease-free survival, and continuous CR were 10.6, 15.5, and 15.9 months, respectively. The probability of overall survival, disease-free survival, and continuous CR at 5 years were 18, 22, and 30%, respectively. CONCLUSIONS: IDAC is a safe and effective postremission therapy for elderly patients with AML.