RESUMO
The term Castleman's disease encompasses a group of rare lymphoproliferative diseases that show histopathological similarities in lymph node biopsy. Diagnostic criteria and a specific ICD-10 code have been available for a few years. Case studies listed at the beginning illustrate that close cooperation between clinicians and pathologists is required to enable a reliable diagnosis. For an optimal histopathological assessment, the pathologist is also dependent on the removal of a complete lymph node. Before distinguishing a potentially fatal multicentric idiopathic Castleman's disease from the resectable unicentric form, which is important in terms of prognosis and treatment, early diagnosis presupposes that Castleman's disease is considered in the differential diagnosis. Various immune phenomena and overlaps with autoimmune diseases can increase the probability of misdiagnosis or undetected cases in the clinical routine of rheumatologists. The intention of the present overview is therefore to point out the similarities with autoimmune diseases that are relevant for differential diagnoses and to point out situations that justify a review of the previous diagnosis.
RESUMO
Autologous haematopoietic SCT with PBSCs is regularly used to restore BM function in patients with multiple myeloma or lymphoma after myeloablative chemotherapy. Twenty-eight experts from the European Group for Blood and Marrow Transplantation developed a position statement on the best approaches to mobilising PBSCs and on possibilities of optimising graft yields in patients who mobilise poorly. Choosing the appropriate mobilisation regimen, based on patients' disease stage and condition, and optimising the apheresis protocol can improve mobilisation outcomes. Several factors may influence mobilisation outcomes, including older age, a more advanced disease stage, the type of prior chemotherapy (e.g., fludarabine or melphalan), prior irradiation or a higher number of prior treatment lines. The most robust predictive factor for poor PBSC collection is the CD34(+) cell count in PB before apheresis. Determination of the CD34(+) cell count in PB before apheresis helps to identify patients at risk of poor PBSC collection and allows pre-emptive intervention to rescue mobilisation in these patients. Such a proactive approach might help to overcome deficiencies in stem cell mobilisation and offers a rationale for the use of novel mobilisation agents.
Assuntos
Mobilização de Células-Tronco Hematopoéticas/métodos , Linfoma/terapia , Mieloma Múltiplo/terapia , Europa (Continente) , Humanos , Transplante AutólogoRESUMO
Monoclonal gammopathy of undetermined significance (MGUS) and monoclonal B lymphocytosis (MBL) are asymptomatic premalignant conditions which can progress to a symptomatic disease state requiring therapy. Considering the high prevalence rate of these disorders, precursor patients are often diagnosed during routine clinical examinations. Only a minor portion of cases progress to overt malignancies, which raises the question of how to identify patients with the probability of progression. In recent years improvements in the understanding of the pathogenesis of both disorders led to the development of risk models and the estimation of the individual risk of progression. The definition of high-risk and low-risk patients allows a tailored clinical management. This report provides information on the biology, risk stratification, diagnosis, and follow-up of patients with MGUS and MBL.
Assuntos
Linfocitose/diagnóstico , Linfocitose/terapia , Gamopatia Monoclonal de Significância Indeterminada/diagnóstico , Gamopatia Monoclonal de Significância Indeterminada/terapia , Mieloma Múltiplo/diagnóstico , Lesões Pré-Cancerosas/diagnóstico , Lesões Pré-Cancerosas/terapia , Humanos , Mieloma Múltiplo/prevenção & controleRESUMO
NOX-A12 is a PEGylated mirror-image oligonucleotide (a so-called Spiegelmer) that binds to CXCL12 (stromal cell-derived factor-1, SDF-1) with high affinity thereby inhibiting CXCL12 signaling on both its receptors, CXCR4 and CXCR7. In animals, NOX-A12 mobilized white blood cells (WBCs) and hematopoietic stem and progenitor cells (HSCs) into peripheral blood (PB). In healthy volunteers, single doses of NOX-A12 had a benign safety profile and also dose-dependently mobilized WBCs and HSCs into PB. HSC peak mobilization reached a plateau at five times the baseline level at an i.v. dose of 5.4 mg/kg. In accordance with the plasma half-life of 38 h, the duration of the WBC and HSC mobilization was long lasting and increased dose-dependently to more than 4 days at the highest dose (10.8 mg/kg). In conclusion, NOX-A12 may be appropriate for therapeutic use in and beyond mobilization of HSCs, e.g., in long-lasting mobilization and chemosensitization of hematological cancer cells.
Assuntos
Quimiocina CXCL12/antagonistas & inibidores , Mobilização de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas/metabolismo , Leucócitos/metabolismo , Oligonucleotídeos/farmacologia , Adolescente , Adulto , Animais , Quimiocina CXCL12/metabolismo , Relação Dose-Resposta a Droga , Feminino , Humanos , Contagem de Leucócitos , Macaca , Masculino , Camundongos , Pessoa de Meia-Idade , Modelos Animais , Oligonucleotídeos/farmacocinética , Adulto JovemRESUMO
BACKGROUND: Cancer patients frequently suffer from gastrointestinal complications. However, a comprehensive, practical and evidence-based guideline on this issue is not yet available. PATIENTS AND METHODS: An expert group was put together by the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO) to develop a guideline on gastrointestinal complications in cancer patients. For each subtopic, a literature search was carried out in PubMed, Medline and Cochrane databases and the strength of recommendation and the quality of the published evidence for major therapeutic strategies were categorized using a modification of the 'Infectious Diseases Society of America' criteria. Consensus discussions were held on each of the topics. RESULTS: Recommendations were made with respect to non-infectious and infectious gastrointestinal complications. For all recommendations, the strength of the recommendation and the level of evidence are presented. CONCLUSION: This guideline is an evidence-based approach to the diagnosis and management of gastrointestinal complications in cancer patients.
Assuntos
Gastroenteropatias/etiologia , Gastroenteropatias/terapia , Neoplasias/complicações , Neoplasias/terapia , Adulto , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Diarreia/etiologia , Diarreia/microbiologia , Diarreia/terapia , Enterocolite/etiologia , Enterocolite/terapia , Febre/etiologia , Febre/terapia , Gastroenteropatias/diagnóstico , Humanos , Neutropenia/etiologia , Neutropenia/terapiaAssuntos
Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Mobilização de Células-Tronco Hematopoéticas/métodos , Compostos Heterocíclicos/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Benzilaminas , Índice de Massa Corporal , Contraindicações , Ciclamos , Feminino , Doença de Hodgkin/patologia , Humanos , Linfoma não Hodgkin/patologia , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/patologia , Obesidade/fisiopatologia , Sobrepeso/fisiopatologia , Estudos Retrospectivos , Magreza/fisiopatologia , Adulto JovemRESUMO
The effectiveness of the novel hematopoietic stem cell mobilizing agent plerixafor was evaluated in nationwide compassionate use programs in 13 European countries. A total of 580 poor mobilizers with non-Hodgkin's lymphoma (NHL), Hodgkin's lymphoma (HL) and multiple myeloma (MM) were enrolled. All patients received plerixafor plus granulocyte CSF with or without chemotherapy. Overall, the collection yield was significantly higher in MM patients (>2.0 × 10(6) CD34+ cells/kg: 81.6%; >5.0 × 10(6) CD34+ cells/kg: 32.0%) than in NHL patients (>2.0 × 10(6) CD34+ cells/kg: 64.8%; >5.0 × 10(6) CD34+ cells/kg: 12.6%; P<0.0001) and also significantly higher in HL patients (>2.0 × 10(6) CD34+ cells/kg: 81.5%; >5.0 × 10(6) CD34+ cells/kg: 22.2%) than in NHL patients (P=0.013). In a subgroup analysis, there were no significant differences in mobilization success comparing patients with diffuse large B-cell lymphoma, follicular lymphoma and mantle cell lymphoma. Our data emphasize the role of plerixafor in poor mobilizers, but further strategies to improve the apheresis yield especially in patients with NHL are required.
Assuntos
Fármacos Anti-HIV/administração & dosagem , Mobilização de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas , Compostos Heterocíclicos/administração & dosagem , Doença de Hodgkin/terapia , Linfoma não Hodgkin/terapia , Mieloma Múltiplo/terapia , Adolescente , Adulto , Idoso , Benzilaminas , Remoção de Componentes Sanguíneos/métodos , Criança , Ciclamos , União Europeia , Feminino , Fator Estimulador de Colônias de Granulócitos , Doença de Hodgkin/sangue , Humanos , Contagem de Leucócitos , Linfoma não Hodgkin/sangue , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/sangue , Transplante HomólogoAssuntos
Mobilização de Células-Tronco Hematopoéticas , Compostos Heterocíclicos/farmacologia , Transplante de Células-Tronco de Sangue Periférico , Receptores CXCR4/antagonistas & inibidores , Antígenos CD34/análise , Benzilaminas , Ciclamos , Fator Estimulador de Colônias de Granulócitos/farmacologia , Humanos , Transplante AutólogoRESUMO
Up to 10% of germ cell tumor patients require salvage high-dose chemotherapy with stem cell support, achieving cure rates in the range of 10-60%. Stem cell mobilization may be difficult in these patients because of multiple lines of treatment known to seriously hamper stem cell recovery. Plerixafor significantly enhances the success of the CD34+ cell harvest, even in cases where prior mobilization attempts have failed. Six germ cell tumor patients provided informed consent and were included in the compassionate use program. All patients were heavily pretreated, with a median of 3.5 prior lines of therapy. All failed prior mobilization with G-CSF in combination with chemotherapy. Five patients yielded a median of 2.6 × 10(6) CD34+ cells per kg body weight in a median of 4 apheresis days when plerixafor was used. Three patients underwent subsequent high-dose chemotherapy with autologous stem cell support. Median time to leukocyte engraftment was 11 days. Median time to platelet engraftment was 12.5 days, both of which are comparable to previous historical data. Accordingly, plerixafor seems to be safe and effective in germ cell tumor patients who have failed prior mobilization therapy. Larger prospective studies are warranted to further assess its use in germ cell cancer.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ensaios de Uso Compassivo , Mobilização de Células-Tronco Hematopoéticas/métodos , Compostos Heterocíclicos/uso terapêutico , Neoplasias Embrionárias de Células Germinativas/terapia , Neoplasias Testiculares/terapia , Adulto , Benzilaminas , Terapia Combinada , Ciclamos , Transplante de Células-Tronco Hematopoéticas , Compostos Heterocíclicos/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Embrionárias de Células Germinativas/sangue , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Neoplasias Embrionárias de Células Germinativas/cirurgia , Seminoma/sangue , Seminoma/diagnóstico por imagem , Seminoma/tratamento farmacológico , Seminoma/terapia , Neoplasias Testiculares/sangue , Neoplasias Testiculares/tratamento farmacológico , Neoplasias Testiculares/cirurgia , Ultrassonografia , Adulto JovemRESUMO
The CXCR4-inhibitor plerixafor mobilizes hematopoietic stem cells amplifying the effects of granulocyte-CSF (G-CSF). Before approval plerixafor was used in a compassionate use program (CUP) for patients who failed a previous mobilization. In the German CUP 60 patients from 23 centers (median age 56.5 years (2-75)) were given 240 µg/kg plerixafor SC 9-11 h before apheresis. A total of 78.3% (47/60) received G-CSF for 4 days before plerixafor administration; 76.6% of those (36/47) yielded at least 2.0 × 10(6) CD34(+) cells/µL. The median cell yield was 3.35 × 10(6) CD34+ cells/kg (0-29.53). Nine patients received plerixafor alone or with G-CSF for less than 4 days mobilizing a median of 3.30 × 10(6) CD34+ cells/kg (1.6-5.6). There was no significant difference between G-CSF application for 4 days and for a shorter period of time (P=0.157). A total of 47 patients received plerixafor plus G-CSF combined with chemotherapy yielding a median of 3.28 × 10(6) CD34+ cells/kg (0-24.79). In all, 40 of 60 patients (66.7%) proceeded to transplantation, and achieved a timely and stable engraftment. Side effects were rare and manageable. In conclusion, mobilization with plerixafor in poor mobilizers is safe and results in a sufficient stem cell harvest in the majority of patients.
Assuntos
Ensaios de Uso Compassivo , Mobilização de Células-Tronco Hematopoéticas/métodos , Compostos Heterocíclicos/uso terapêutico , Doença de Hodgkin/terapia , Linfoma não Hodgkin/terapia , Mieloma Múltiplo/terapia , Adolescente , Adulto , Idoso , Benzilaminas , Remoção de Componentes Sanguíneos/métodos , Criança , Pré-Escolar , Terapia Combinada , Ciclamos , Feminino , Alemanha , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Compostos Heterocíclicos/efeitos adversos , Doença de Hodgkin/sangue , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/cirurgia , Humanos , Linfoma não Hodgkin/sangue , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/cirurgia , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/sangue , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/cirurgia , Resultado do Tratamento , Adulto JovemRESUMO
This report describes the first investigational use of plerixafor in Europe and the determination of tumor cell mobilization by polymerase chain-reaction after plerixafor treatment in a subset of patients with multiple myeloma (MM). Thirty-five patients (31 MM and 4 NHL) received granulocyte colony-stimulating factor (G-CSF) (10 microg/kg) each morning for 4 days. Starting the evening of Day 4, patients recieved plerixafor 0.24 mg/kg. Apheresis was initiated 10-11 h later, in the morning of Day 5. This regimen of G-CSF treatment each morning before apheresis and plerixafor treatment in the evening was repeated for up to 5 consecutive days. Mobilization with plerixafor and G-CSF resulted in a median 2.6-fold increase in peripheral blood (PB) CD34+ cell count compared with before plerixafor treatment. All patients collected > or =2 x 10(6) CD34+ cells/kg and 32 of 35 patients collected > or =5 x 10(6) CD34+ cells/kg. After plerixafor treatment, 3 of 7 patients had a small increase and 4 of 7 patients had a small decrease in PB tumor cells. No G-CSF was given post transplant. The median number of days to polymorphonuclear leukocyte and platelet engraftment was 14.0 and 11.0, respectively. There were no reports of graft failure. Plerixafor was generally well tolerated. Mobilization of PB CD34+ cells was consistent with previous clinical trials. The addition of plerixafor did not significantly increase the relative number of PB MM tumor cells.
Assuntos
Mobilização de Células-Tronco Hematopoéticas/métodos , Compostos Heterocíclicos/uso terapêutico , Linfoma não Hodgkin/terapia , Mieloma Múltiplo/terapia , Adulto , Idoso , Antígenos CD34/sangue , Benzilaminas , Contagem de Células Sanguíneas , Remoção de Componentes Sanguíneos/métodos , Ciclamos , Feminino , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Resultado do TratamentoAssuntos
Doenças Hematológicas/terapia , Neoplasias Hematológicas/terapia , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada , Fibrinolíticos/uso terapêutico , Doenças Hematológicas/diagnóstico , Neoplasias Hematológicas/diagnóstico , Hemoglobinúria Paroxística/diagnóstico , Hemoglobinúria Paroxística/terapia , Humanos , Morfolinas/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Rivaroxabana , Tiofenos/uso terapêutico , Tromboembolia/terapiaAssuntos
Corticosteroides/uso terapêutico , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doença Enxerto-Hospedeiro/mortalidade , Transplante de Células-Tronco Hematopoéticas/estatística & dados numéricos , Agonistas Mieloablativos/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Análise de Sobrevida , Condicionamento Pré-Transplante/métodos , Transplante HomólogoRESUMO
Based on Bayesian statistics and the Bayesian theory of measurement uncertainty, characteristic limits such as the decision threshold, detection limit and limits of a confidence interval can be calculated taking into account all sources of uncertainty. This approach consists of the complete evaluation of a measurement according to the ISO Guide to the Expression of Uncertainty in Measurement (GUM) and the successive determination of the characteristic limits by using the standard uncertainty obtained from the evaluation. This procedure is elaborated here for several particular models of evaluation. It is, however, so general that it allows for a large variety of applications to similar measurements. It is proposed for the revision of those parts of DIN 25482 and ISO 11929 that are still based on conventional statistics and, therefore, do not allow to take completely into account all the components of measurement uncertainty in the calculation of the characteristic limits.
Assuntos
Radiação Ionizante , Radiometria/métodos , Algoritmos , Teorema de Bayes , Calibragem , Intervalos de Confiança , Modelos Estatísticos , Modelos Teóricos , Probabilidade , EspectrofotometriaRESUMO
Pneumonia remains the number one cause of death from infectious diseases in Western Europe and the United States despite the introduction of potent broad-spectrum antibiotics. Granulocyte colony-stimulating factor is considered to improve host defense during infection and may be an effective adjunctive in the treatment of severe infections. We examined the efficacy of granulocyte colony-stimulating factor (r-metHUG-CSF, filgrastim) with regard to clinical response in non-neutropenic ICU patients with nosocomial pneumonia in a prospective, randomized, placebo-controlled trial. 28 patients with newly diagnosed nosocomial pneumonia were randomly assigned to receive 300-480 microg filgrastim or placebo subcutaneously for up to seven days. Study endpoints were death within 15 days, duration of antibiotic therapy and occurrence of serious adverse events (SAE). No significant differences were observed in respect of 15-day (filgrastim1/12 vs. placebo 2/16) or 30-day mortality (1/12 vs.4/16, p=0.355), and length of antibiotic treatment (13.5 vs.11.5 days, p=0.985). Sepsis developed in 1/12 patients in the filgrastim and 6/16 patients in the placebo group (p=0.184). None of the patients developed ARDS or any other SAE related to the study medication. Filgrastim is safe in non-neutropenic ICU patients with nosocomial pneumonia. A benefit of filgrastim with regard to clinical endpoints could not be observed, while there was a trend toward reduced sepsis rate.
Assuntos
Infecção Hospitalar/tratamento farmacológico , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Neutropenia , Pneumonia/tratamento farmacológico , Adulto , Idoso , Infecção Hospitalar/mortalidade , Infecção Hospitalar/fisiopatologia , Feminino , Filgrastim , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Nível de Saúde , Humanos , Injeções Subcutâneas , Masculino , Pessoa de Meia-Idade , Neutropenia/complicações , Pneumonia/complicações , Pneumonia/mortalidade , Pneumonia/fisiopatologia , Proteínas Recombinantes , Taxa de SobrevidaRESUMO
Severe fungal infections remain a significant cause of morbidity and mortality in neutropenic patients undergoing dose-intensive chemotherapy for malignant diseases. Chronic disseminated candidiasis (CDC) is a life-threatening complication in neutropenic patients because of the lack of responsive hematopoietic precursor cells. Resolution of Candida organ lesions after hematopoietic reconstitution may take months. Here, we report the case of a 19-year-old neutropenic woman with relapsed acute myelogenous leukemia and candidiasis of liver, spleen, and kidneys. Antifungal treatment was initiated using fluconazole and caspofungin but was changed to itraconazole and caspofungin. Despite elevated C-reactive protein (CRP) levels and detectable Candida organ lesions, antileukemic therapy was restarted with interleukin 2 at the same time as antimicrobial treatment. Eight weeks after the start of interleukin therapy, CRP levels and organ lesions were decreased significantly irrespective of continuing neutropenia. This case report describes the successful treatment of CDC during neutropenia using combination antifungal therapy and suggests controlled studies to establish optimal therapeutic strategies.
Assuntos
Candidíase/tratamento farmacológico , Itraconazol/administração & dosagem , Leucemia Mieloide Aguda/complicações , Neutropenia/etiologia , Peptídeos Cíclicos , Peptídeos/administração & dosagem , Adulto , Antifúngicos/administração & dosagem , Candidíase/etiologia , Candidíase/patologia , Caspofungina , Doença Crônica , Equinocandinas , Feminino , Humanos , Interleucina-2/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Lipopeptídeos , Infecções Oportunistas/tratamento farmacológico , Resultado do TratamentoRESUMO
The discovery of granulocyte colony-stimulating factor (G-CSF) and its potential to regulate neutrophil production and function in the inflammatory process has opened an exciting new era for the supportive care of patients with hematological and malignant diseases. Extensive experience has been gained worldwide with G-CSF therapy, and G-CSF is widely employed clinically, primarily because the safety profile appears to be fairly innocuous. A broad consensus has emerged regarding the clinical utility of G-CSF in neutropenic conditions due to chemotherapy. Furthermore, much interest has focused on the use of G-CSF to mobilize CD34+ hematopoietic stem cells from the marrow to the peripheral blood for use in hematopoietic transplantation. The promising results with G-CSF have promoted further studies, e.g., in immunocompetent patients or in granulocyte transfusion therapy. Here, we review the potential clinical role of G-CSF and describe its future perspectives.
Assuntos
Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Neutrófilos/fisiologia , Granulócitos/efeitos dos fármacos , Granulócitos/fisiologia , Humanos , Transfusão de Leucócitos , Neutropenia/tratamento farmacológico , Neutrófilos/efeitos dos fármacos , Proteínas RecombinantesRESUMO
Opportunistic fungal infections and antibiotic-refractory bacterial infections remain important causes of morbidity and mortality in neutropenic individuals. Furthermore, the expanding use of dose-intensive cancer treatment strategies has increased the frequency of prolonged neutropenia. Therefore, the transfusion of granulocytes should be a logical therapeutic approach. Substantial progress has been made in the field of granulocyte transfusion therapy during the past decade. Interest in granulocyte transfusion therapy has been rekindled by both the use of hematopoietic growth factors to mobilize neutrophils and modern leukapheresis techniques. Moreover, promising results were observed in the use of community donors and in granulocyte storage experiments, which could enhance the ability of blood banks for institution of granulocyte concentrates. Recent clinical trials suggest that granulocyte transfusion therapy may be effective and well-tolerated in the neutropenic patient affected by life-threatening infections. These results must be confirmed in controlled, clinical trials.