RESUMEN
The novel coronavirus SARS-CoV-2 and the associated infectious disease COVID-19 pose a significant challenge to healthcare systems worldwide. Patients with cancer have been identified as a high-risk population for severe infections, rendering prophylaxis and treatment strategies for these patients particularly important. Rapidly evolving clinical research, resulting in the recent advent of various vaccines and therapeutic agents against COVID-19, offers new options to improve care and protection of cancer patients. However, ongoing epidemiological changes and rise of new virus variants require repeated revisions and adaptations of prophylaxis and treatment strategies to meet these new challenges. Therefore, this guideline provides an update on evidence-based recommendations with regard to vaccination, pharmacological prophylaxis and treatment of COVID-19 in cancer patients in light of the currently dominant omicron variants. It was developed by an expert panel of the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO) based on a critical review of the most recent available data.
Asunto(s)
COVID-19 , Enfermedades Transmisibles , Neoplasias , Humanos , COVID-19/prevención & control , COVID-19/complicaciones , SARS-CoV-2 , Neoplasias/terapia , Neoplasias/tratamiento farmacológico , Enfermedades Transmisibles/complicaciones , Enfermedades Transmisibles/tratamiento farmacológico , VacunaciónRESUMEN
Patients with cancer are at increased risk of infection due to disease-associated or therapy-induced immunosuppression. Taking into account globally increasing antimicrobial resistance rates and negative effects associated with antibiotic treatments, the effective, appropriate and guideline-conform use of anti-infectives must be promoted in this clinical setting. The application of antibacterial prophylaxis should be limited to high-risk patients. Infection diagnostics and therapeutic strategies differ depending on the extent of expected immunosuppression and the patient's individual risk factors.
RESUMEN
Clinical reactivations of herpes simplex virus or varicella zoster virus occur frequently among patients with malignancies and manifest particularly as herpes simplex stomatitis in patients with acute leukaemia treated with intensive chemotherapy and as herpes zoster in patients with lymphoma or multiple myeloma. In recent years, knowledge on reactivation rates and clinical manifestations has increased for conventional chemotherapeutics as well as for many new antineoplastic agents. This guideline summarizes current evidence on herpesvirus reactivation in patients with solid tumours and hematological malignancies not undergoing allogeneic or autologous hematopoietic stem cell transplantation or other cellular therapy including diagnostic, prophylactic, and therapeutic aspects. Particularly, strategies of risk adapted pharmacological prophylaxis and vaccination are outlined for different patient groups. This guideline updates the guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO) from 2015 "Antiviral prophylaxis in patients with solid tumours and haematological malignancies" focusing on herpes simplex virus and varicella zoster virus.
Asunto(s)
Neoplasias Hematológicas/virología , Herpes Genital/terapia , Herpes Simple/terapia , Neoplasias/virología , Infección por el Virus de la Varicela-Zóster/terapia , Activación Viral , Aciclovir/uso terapéutico , Antivirales/uso terapéutico , Manejo de la Enfermedad , Alemania , Herpes Genital/diagnóstico , Herpes Genital/prevención & control , Herpes Simple/diagnóstico , Herpes Simple/prevención & control , Herpesvirus Humano 1/efectos de los fármacos , Herpesvirus Humano 1/aislamiento & purificación , Herpesvirus Humano 1/fisiología , Herpesvirus Humano 2/efectos de los fármacos , Herpesvirus Humano 2/aislamiento & purificación , Herpesvirus Humano 2/fisiología , Herpesvirus Humano 3/efectos de los fármacos , Herpesvirus Humano 3/aislamiento & purificación , Herpesvirus Humano 3/fisiología , Humanos , Vacunación , Infección por el Virus de la Varicela-Zóster/diagnóstico , Infección por el Virus de la Varicela-Zóster/prevención & control , Activación Viral/efectos de los fármacosRESUMEN
Hematologic and oncologic patients with chemo- or immunotherapy-related immunosuppression are at substantial risk for bacterial infections and Pneumocystis jirovecii pneumonia (PcP). As bacterial resistances are increasing worldwide and new research reshapes our understanding of the interactions between the human host and bacterial commensals, administration of antibacterial prophylaxis has become a matter of discussion. This guideline constitutes an update of the 2013 published guideline of the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO). It gives an overview about current strategies for antibacterial prophylaxis in cancer patients while taking into account the impact of antibacterial prophylaxis on the human microbiome and resistance development. Current literature published from January 2012 to August 2020 was searched and evidence-based recommendations were developed by an expert panel. All recommendations were discussed and approved in a consensus conference of the AGIHO prior to publication. As a result, we present a comprehensive update and extension of our guideline for antibacterial and PcP prophylaxis in cancer patients.
Asunto(s)
Antibacterianos/uso terapéutico , Neoplasias Hematológicas/complicaciones , Pneumocystis carinii/efectos de los fármacos , Neumonía por Pneumocystis/prevención & control , Antineoplásicos/uso terapéutico , Farmacorresistencia Bacteriana , Fluoroquinolonas/uso terapéutico , Alemania , Neoplasias Hematológicas/tratamiento farmacológico , Hematología , Humanos , Oncología Médica , Microbiota/efectos de los fármacos , Neumonía por Pneumocystis/complicaciones , Sociedades MédicasRESUMEN
The worldwide spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the associated infectious coronavirus disease (COVID-19) has posed a unique challenge to medical staff, patients and their families. Patients with cancer, particularly those with haematologic malignancies, have been identified to be at high risk to develop severe COVID-19. Since publication of our previous guideline on evidence-based management of COVID-19 in patients with cancer, research efforts have continued and new relevant data has come to light, maybe most importantly in the field of vaccination studies. Therefore, an update of our guideline on several clinically important topics is warranted. Here, we provide a concise update of evidence-based recommendations for rapid diagnostics, viral shedding, vaccination and therapy of COVID-19 in patients with cancer. This guideline update was prepared by the Infectious Diseases Working Party (AGIHO) of the German Society for Haematology and Medical Oncology by critically reviewing the currently available data on these topics applying evidence-based medicine criteria.
Asunto(s)
Prueba de COVID-19/normas , Vacunas contra la COVID-19/uso terapéutico , COVID-19 , Neoplasias , SARS-CoV-2/fisiología , Esparcimiento de Virus/fisiología , Antivirales/uso terapéutico , COVID-19/diagnóstico , COVID-19/epidemiología , COVID-19/terapia , COVID-19/virología , Prueba de COVID-19/métodos , Medicina Basada en la Evidencia/normas , Medicina Basada en la Evidencia/estadística & datos numéricos , Alemania/epidemiología , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/epidemiología , Neoplasias Hematológicas/terapia , Neoplasias Hematológicas/virología , Hematología/organización & administración , Hematología/normas , Humanos , Inmunización Pasiva/métodos , Inmunización Pasiva/normas , Infectología/organización & administración , Infectología/normas , Oncología Médica/organización & administración , Oncología Médica/normas , Neoplasias/diagnóstico , Neoplasias/epidemiología , Neoplasias/terapia , Neoplasias/virología , SARS-CoV-2/inmunología , Sociedades Médicas/normas , Vacunación/métodos , Vacunación/normas , Sueroterapia para COVID-19RESUMEN
Since its first detection in China in late 2019 the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the associated infectious disease COVID-19 continue to have a major impact on global healthcare and clinical practice. Cancer patients, in particular those with haematological malignancies, seem to be at an increased risk for a severe course of infection. Deliberations to avoid or defer potentially immunosuppressive therapies in these patients need to be balanced against the overarching goal of providing optimal antineoplastic treatment. This poses a unique challenge to treating physicians. This guideline provides evidence-based recommendations regarding prevention, diagnostics and treatment of SARS-CoV-2 infection and COVID-19 as well as strategies towards safe antineoplastic care during the COVID-19 pandemic. It was prepared by the Infectious Diseases Working Party (AGIHO) of the German Society for Haematology and Medical Oncology (DGHO) by critically reviewing the currently available data on SARS-CoV-2 and COVID-19 in cancer patients applying evidence-based medicine criteria.
Asunto(s)
Antineoplásicos/uso terapéutico , Betacoronavirus/aislamiento & purificación , Infecciones por Coronavirus/complicaciones , Atención a la Salud/normas , Práctica Clínica Basada en la Evidencia/normas , Neoplasias/tratamiento farmacológico , Neumonía Viral/complicaciones , Guías de Práctica Clínica como Asunto/normas , COVID-19 , Infecciones por Coronavirus/transmisión , Infecciones por Coronavirus/virología , Manejo de la Enfermedad , Alemania/epidemiología , Humanos , Neoplasias/epidemiología , Neoplasias/virología , Pandemias , Neumonía Viral/transmisión , Neumonía Viral/virología , Pronóstico , SARS-CoV-2 , Sociedades MédicasRESUMEN
BACKGROUND: Fludarabine-based chemoimmunotherapy with rituximab is frequently used in patients with indolent and mantle-cell lymphomas who relapse after alkylating chemotherapy. We aimed to compare the efficacy and safety of rituximab with bendamustine or fludarabine in patients with relapsed, indolent, non-Hodgkin lymphoma and mantle-cell lymphoma. METHODS: For this randomised, non-inferiority, open-label, phase 3 trial, we recruited patients from 55 centres in Germany, who were subsequently randomised centrally according to prespecified randomisation lists with permuted blocks of randomly variable block size to rituximab (375 mg/m(2), day 1) plus either bendamustine (90 mg/m(2), days 1 and 2) or fludarabine (25 mg/m(2), days 1-3) every 28 days for a maximum of six 28-day cycles. Patients were aged 18 years or older with a WHO performance status of 0-2 and had relapsed or refractory indolent or mantle-cell lymphoma; patients refractory to regimens that included rituximab, bendamustine, or purine analogue drugs were excluded. Patients were stratified by histological subtypes of lymphoma and by their latest previous therapies. Treatment allocation was not masked. The primary endpoint was progression-free survival and the final analysis was completed per protocol. Non-inferiority of bendamustine plus rituximab versus fludarabine plus rituximab was defined as a difference of less than 15% in 1-year progression-free survival. The protocol was amended in July, 2006, after approval of rituximab maintenance (375 mg/m(2) every 3 months for up to 2 years), which was then given to patients achieving a response to either trial treatment. This study is registered with ClinicalTrials.gov, number NCT01456351 (closed to enrolment, follow-up is ongoing). FINDINGS: Between Oct 8, 2003, and Aug 5, 2010, we randomly assigned 230 patients to treatment groups (116 bendamustine plus rituximab, 114 fludarabine plus rituximab). 11 patients were excluded for protocol violations and were not followed up further (two in the bendamustine plus rituximab group and nine in the fludarabine plus rituximab group). Thus, 219 patients were included in the per-protocol analysis (114 bendamustine plus rituximab, 105 fludarabine plus rituximab). 1-year progression-free survival with bendamustine plus rituximab was 0·76 (95% CI 0·68-0·84) and 0·48 (0·39-0·58) with fludarabine plus rituximab (non-inferiority p<0·0001). At a median follow-up of 96 months (IQR 73·2-112·9), median progression-free survival with bendamustine plus rituximab was 34·2 months (95% CI 23·5-52·7) and 11·7 months (8·0-16·1) with fludarabine plus rituximab (hazard ratio [HR] 0·54 [95% CI 0·38-0·72], log-rank test p<0·0001). Safety outcomes were similar in both groups, with 46 serious adverse events recorded (23 in the bendamustine plus rituximab group and 23 in the fludarabine plus rituximab group), most commonly myelosuppression and infections. INTERPRETATION: In combination with rituximab, bendamustine was more effective than fludarabine, suggesting that bendamustine plus rituximab may be the preferred treatment option for patients with relapsed indolent and mantle-cell lymphomas. FUNDING: Roche Pharma AG, Ribosepharm GmbH, Mundipharma GmbH, Studiengruppe indolente Lymphome (StiL).
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma de Células del Manto/tratamiento farmacológico , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Clorhidrato de Bendamustina/administración & dosificación , Clorhidrato de Bendamustina/efectos adversos , Supervivencia sin Enfermedad , Femenino , Humanos , Infecciones/inducido químicamente , Masculino , Persona de Mediana Edad , Recurrencia , Retratamiento , Rituximab/administración & dosificación , Rituximab/efectos adversos , Tasa de Supervivencia , Resultado del Tratamiento , Vidarabina/administración & dosificación , Vidarabina/efectos adversos , Vidarabina/análogos & derivadosRESUMEN
Reactivation of viral infections is common in patients with solid tumour or haematological malignancy. Incidence and severity depend on the extent of cellular immunosuppression. Antiviral prophylaxis may be effective to prevent viral reactivation. In 2006, the Infectious Diseases Working Party of German Society for Hematology and Medical Oncology (DGHO) published guidelines for antiviral prophylaxis in these patient populations. Here, we present an update of these guidelines for patients with solid and haematological malignancies undergoing antineoplastic treatment but not allogeneic stem cell transplantation. Relevant literature for reactivation of different viruses (herpes simplex virus (HSV), varicella zoster virus (VZV), hepatitis B virus (HBV) and respiratory viruses) is discussed to provide evidence-based recommendations for clinicians taking care of this patient population. We recommend a risk-adapted approach with (val)acyclovir against HSV and VZV in patients treated with alemtuzumab, bortezomib or purine analogues. Seasonal vaccination against influenza is recommended for all patients with solid or haematological malignancies regardless of antineoplastic therapy. Hepatitis B screening is recommended in lymphoproliferative disorders, acute leukaemia, and breast cancer, and during treatment with monoclonal anti-B-cell antibodies, anthracyclines, steroids and in autologous stem cell transplantation. In those with a history of hepatitis B prophylactic lamivudine, entecavir or nucleotide analogues as adefovir are recommended to prevent reactivation.
Asunto(s)
Antivirales/uso terapéutico , Neoplasias de la Mama/terapia , Leucemia/terapia , Virosis/prevención & control , Enfermedad Aguda , Antineoplásicos/uso terapéutico , Autoinjertos , Femenino , Alemania , Hematología , Humanos , Masculino , Oncología Médica , Guías de Práctica Clínica como Asunto , Sociedades Médicas , Trasplante de Células MadreRESUMEN
The patient granulocyte-colony stimulating factor (G-CSF) response is represented by the leukocyte peak in the blood induced by a single dose of G-CSF after chemotherapy, and is correlated with subsequent neutropenic infection risk. General patterns for a meaningful risk group stratification, have not yet been determined. Two independent data sets including a total of 306 cases with myeloma or lymphoma and autologous blood stem cell transplant were available. An infection susceptibility curve plotted according to ranked G-CSF responses from a multicenter study reproduced and validated a curve from the previous single center. Two trend changes were seen within these curves at around 11,000 and 22,000 leukocytes/µL, which separated three groups with a high, medium and low risk of infection. While G-CSF response is related to the consecutive duration of neutropenia, it retains additional independent predictive information for infection risk (p<0.0001) and, more important, is a tool available before the onset of the critical period.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/métodos , Linfoma/terapia , Mieloma Múltiple/terapia , Neutropenia/prevención & control , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Infecciones Bacterianas/etiología , Infecciones Bacterianas/prevención & control , Terapia Combinada , Relación Dosis-Respuesta a Droga , Femenino , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Recuento de Leucocitos , Modelos Lineales , Masculino , Persona de Mediana Edad , Análisis Multivariante , Micosis/etiología , Micosis/prevención & control , Neutropenia/etiología , Factores de Riesgo , Factores de Tiempo , Trasplante Autólogo , Resultado del TratamientoRESUMEN
Invasive fungal infections cause substantial morbidity and mortality in immunocompromised patients, particularly in those with haematological malignancies and recipients of allogeneic haematopoietic stem cell transplantation. Difficulties in diagnosing invasive fungal infections and subsequent delays in treatment initiation lead to unfavourable outcomes and emphasise the importance of prophylaxis. Since the recommendations of the Infectious Diseases Working Party of the German Society for Haematology and Oncology in 2009, results of 14 additional clinical studies have been published comprising 2,899 patients and initiating this update. Key recommendations for adult patients are as follows: Posaconazole remains the drug of choice during remission-induction chemotherapy in acute myeloid leukaemia, myelodysplastic syndrome and allogeneic haematopoietic stem cell transplantation with graft versus host disease (AI). In the pre-engraftment period of allogeneic transplantation, several antifungals are appropriate and can be recommended with equal strength: voriconazole (BI), micafungin (BI), fluconazole (BI) and posaconazole (BII). There is poor evidence regarding antifungal prophylaxis in the post-engraftment period of allogeneic haematopoietic stem cell transplantation if no steroids for treatment of graft versus host disease are required. Aerosolised liposomal amphotericin B inhalation in conjunction with fluconazole can be used in patients with prolonged neutropenia (BII).
Asunto(s)
Antifúngicos/uso terapéutico , Quimioprevención , Neoplasias Hematológicas/tratamiento farmacológico , Micosis/prevención & control , Guías de Práctica Clínica como Asunto , Prevención Primaria/normas , Adulto , Azoles/uso terapéutico , Quimioprevención/métodos , Quimioprevención/normas , Alemania , Humanos , Huésped Inmunocomprometido , Infecciones Oportunistas/prevención & control , Prevención Primaria/métodos , Sociedades Médicas/normasRESUMEN
More than 18,000 autolgous transplantation were performed in Europe in the year 2009. It as a routine procedure in experienced centres. Even if there is a low mortality rate, infections are a major issue after transplantation, occurring in more than 60 % of the patients. In this review we discuss all aspects of infections after autologous stem transplantation, including epidemiology, diagnostics, therapeutic algorithms, prophylaxis and supportive therapy.
Asunto(s)
Antiinfecciosos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Enfermedades Transmisibles/tratamiento farmacológico , Fiebre/tratamiento farmacológico , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Guías de Práctica Clínica como Asunto , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Enfermedades Transmisibles/epidemiología , Relación Dosis-Respuesta a Droga , Alemania , Hematología/legislación & jurisprudencia , Hematología/organización & administración , Trasplante de Células Madre Hematopoyéticas/estadística & datos numéricos , Humanos , Oncología Médica/legislación & jurisprudencia , Oncología Médica/organización & administración , Medicina del Trabajo/legislación & jurisprudencia , Medicina del Trabajo/organización & administración , Sociedades Médicas , Trasplante Autólogo/efectos adversos , Trasplante Autólogo/estadística & datos numéricosRESUMEN
The individual risk of infection and requirements for medical treatment after high-dose chemotherapy have been unpredictable. In this prospective, multicenter, open-label study we investigated the potential of granulocyte colony-stimulating factor (G-CSF) responsiveness as a predictor. A total of 168 patients with multiple myeloma or lymphoma received a single dose of subcutaneous G-CSF (lenograstim, 263 µg) after high-dose chemotherapy. Highly variable leukocyte peaks were measured and grouped as low (quartile 1; leukocytes 100-10 100/µL), medium (quartile 2; leukocytes > 10 100-18 300/µL), and high (quartiles 3/4; leukocytes > 18 300-44 800/µL). G-CSF responsiveness (low vs medium vs high) was inversely correlated with febrile neutropenia (77% vs 60% vs 48%; P = .0037); the rate of infection, including fever of unknown origin (91% vs 67% vs 54%; P < .0001); days with intravenous antibiotics (9 vs 6 vs 5; P < .0001); and antifungal therapy (P = .042). In multivariate analysis, G-CSF responsiveness remained the only factor significantly associated with infection (P = .016). In addition, G-CSF responsiveness was inversely correlated with grade 3/4 oral mucositis (67% vs 33% vs 23%; P < .0001). G-CSF responsiveness appears as a signature of the myeloid marrow reserve predicting defense against neutropenic infection after intensive chemotherapy. This study is registered at http://www.clinicaltrials.gov as NCT01085058.
Asunto(s)
Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Factor Estimulante de Colonias de Granulocitos , Infecciones/etiología , Linfoma/complicaciones , Linfoma/tratamiento farmacológico , Mieloma Múltiple/complicaciones , Mieloma Múltiple/tratamiento farmacológico , Adolescente , Adulto , Anciano , Femenino , Humanos , Infecciones/sangre , Lenograstim , Linfoma/sangre , Masculino , Melfalán/administración & dosificación , Melfalán/efectos adversos , Persona de Mediana Edad , Mieloma Múltiple/sangre , Análisis Multivariante , Neutropenia/sangre , Neutropenia/etiología , Trasplante de Células Madre de Sangre Periférica , Valor Predictivo de las Pruebas , Pronóstico , Estudios Prospectivos , Proteínas Recombinantes , Factores de Riesgo , Adulto JovenRESUMEN
Although B-cell chronic lymphocytic leukemia (CLL) is treatable, it remains an incurable disease and most patients inevitably suffer relapse. Many therapeutic options exist for those requiring therapy, including monoclonal antibodies and stem cell transplantation, but remissions tend to last shorter in the course of the disease. Targeting the cell cycle has recently been realized to be an attractive therapeutic approach in solid and hematological malignancies, and the proliferative nature of B-CLL is increasingly accepted. Here, we report data on a phase II pilot trial with the oral mammalian target of rapamycin (mTOR) inhibitor RAD001 5 mg/daily in patients with advanced B-CLL who had progressive disease after at least two lines of treatment. After treatment of seven patients, this trial was stopped because of toxicity concerns, although some degree of activity was observed (one partial remission, three patients with stable disease). Interestingly, cyclin E expression decreased in responding patients. Further strategies of mTOR inhibition by RAD001 in B-CLL should focus on different treatment schedules, adequate anti-infectious prophylaxis, or combinations with cytotoxic drugs.
Asunto(s)
Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Proteínas Quinasas/fisiología , Sirolimus/análogos & derivados , Ciclo Celular/efectos de los fármacos , Ciclo Celular/fisiología , Everolimus , Humanos , Leucemia Linfocítica Crónica de Células B/mortalidad , Leucemia Linfocítica Crónica de Células B/patología , Proyectos Piloto , Neumonía/inducido químicamente , Neumonía/diagnóstico , Sirolimus/efectos adversos , Sirolimus/farmacología , Sirolimus/uso terapéutico , Serina-Treonina Quinasas TORRESUMEN
There is no widely accepted standard for antifungal prophylaxis in patients with hematologic malignancies. The Infectious Diseases Working Party of the German Society for Haematology and Oncology assigned a committee of hematologists and infectious disease specialists to develop recommendations. Literature data bases were systematically searched for clinical trials on antifungal prophylaxis. The studies identified were shared within the committee. Data were extracted by two of the authors (OAC and MSi). The consensus process was conducted by email communication. Finally, a review committee discussed the proposed recommendations. After consensus was established the recommendations were finalized. A total of 86 trials were identified including 16,922 patients. Only a few trials yielded significant differences in efficacy. Fluconazole 400 mg/d improved the incidence rates of invasive fungal infections and attributable mortality in allogeneic stem cell recipients. Posaconazole 600 mg/d reduced the incidence of IFI and attributable mortality in allogeneic stem cell recipients with severe graft versus host disease, and in patients with acute myelogenous leukemia or myelodysplastic syndrome additionally reduced overall mortality. Aerosolized liposomal amphotericin B reduced the incidence rate of invasive pulmonary aspergillosis. Posaconazole 600 mg/d is recommended in patients with acute myelogenous leukemia/myelodysplastic syndrome or undergoing allogeneic stem cell recipients with graft versus host disease for the prevention of invasive fungal infections and attributable mortality (Level A I). Fluconazole 400 mg/d is recommended in allogeneic stem cell recipients until development of graft versus host disease only (Level A I). Aerosolized liposomal amphotericin B is recommended during prolonged neutropenia (Level B II).
Asunto(s)
Neoplasias Hematológicas/complicaciones , Micosis/complicaciones , Micosis/prevención & control , Antifúngicos/uso terapéutico , Alemania/epidemiología , Neoplasias Hematológicas/epidemiología , Neoplasias Hematológicas/cirugía , Hematología , Trasplante de Células Madre Hematopoyéticas , Humanos , Oncología Médica , Micosis/tratamiento farmacológico , Micosis/epidemiología , Guías de Práctica Clínica como Asunto , Sociedades Médicas , Trasplante HomólogoRESUMEN
Advanced age alone should never be the reason for refusing elderly people an effective oncological therapy which could improve their quality of life and possibly also meaningfully extend their survival. However, age-related physiological organ changes and potential cognitive, emotional and social problems must be precisely analyzed before beginning a therapy. Only then can a decision be made for a specific tumour therapy or perhaps symptom management with supportive measures. Treatability is evaluated using test instruments that have been developed for geriatric assessment.
Asunto(s)
Evaluación Geriátrica , Neoplasias/terapia , Factores de Edad , Anciano , Anciano de 80 o más Años , Anemia/tratamiento farmacológico , Antineoplásicos/administración & dosificación , Antineoplásicos/uso terapéutico , Eritropoyetina/uso terapéutico , Humanos , Esperanza de Vida , Persona de Mediana Edad , Neoplasias/tratamiento farmacológico , Neoplasias/mortalidad , Neoplasias/radioterapia , Neoplasias/cirugía , Cuidados Paliativos , Selección de Paciente , Pronóstico , Calidad de Vida , Factores de RiesgoRESUMEN
BACKGROUND: Safety, tolerability and efficacy of itraconazole and amphotericin B (AMB) were compared for empirical antifungal treatment of febrile neutropenic cancer patients. PATIENTS AND METHODS: In an open, randomised study, 162 patients with at least 72 h of antimicrobial treatment received either intravenous followed by oral itraconazole suspension or intravenous AMB for a maximum of 28 days. Permanent discontinuation of study medication due to any adverse event was the primary safety parameter. Efficacy parameters included response and success rate for both treatment groups. RESULTS: Significantly fewer itraconazole patients discontinued treatment due to any adverse event (22.2 vs. 56.8% AMB; p < 0.0001). The main reason for discontinuation was a rise in serum creatinine (1.2% itraconazole vs. 23.5% AMB). Renal toxicity was significantly higher and more drug-related adverse events occurred in the AMB group. Intention-to-treat (ITT) analysis showed favourable efficacy for itraconazole: response and success rate were both significantly higher than for AMB (61.7 vs. 42% and 70.4 vs. 49.3%, both p < 0.0001). Treatment failure was markedly reduced in itraconazole patients (25.9 vs. 43.2%), largely due to the better tolerability. CONCLUSIONS: Itraconazole was tolerated significantly better than conventional AMB and also showed advantages regarding efficacy. This study confirms the role of itraconazole as a useful and safe agent in empirical antifungal therapy of febrile neutropenic cancer patients.
Asunto(s)
Anfotericina B/efectos adversos , Antifúngicos/efectos adversos , Fiebre de Origen Desconocido/tratamiento farmacológico , Neoplasias Hematológicas/tratamiento farmacológico , Itraconazol/efectos adversos , Micosis/tratamiento farmacológico , Neutropenia/tratamiento farmacológico , Infecciones Oportunistas/tratamiento farmacológico , Administración Oral , Adolescente , Adulto , Anciano , Anfotericina B/uso terapéutico , Antifúngicos/uso terapéutico , Estudios Cruzados , Empirismo , Femenino , Fiebre de Origen Desconocido/etiología , Alemania , Humanos , Infusiones Intravenosas , Itraconazol/uso terapéutico , Masculino , Persona de Mediana Edad , Pacientes Desistentes del Tratamiento/estadística & datos numéricos , Resultado del TratamientoRESUMEN
A sequential regimen of chemotherapy, reduced-intensity conditioning (RIC) for allogeneic stem cell transplantation (SCT), and prophylactic donor lymphocyte transfusion (pDLT) was studied in 103 patients with refractory acute myeloid leukemia (AML). According to published criteria, refractoriness was defined by primary induction failure (PIF; n = 37), early (n = 53), refractory (n = 8), or second (n = 5) relapse. Chemotherapy consisted of fludarabine (4 x 30 mg/m(2)), cytarabine (4 x 2 g/m(2)), and amsacrine (4 x 100 mg/m(2)), followed 4 days later by RIC, comprising 4 Gy total body irradiation (TBI), cyclophosphamide, and antithymocyte globulin. Patients without graft-versus-host disease (GvHD) at day +120 received pDLT in escalating doses. Patients' median age was 51.8 years. Before conditioning, 99 patients had active disease, 3 were aplastic, 1 was in second complete remission (CR2). Forty-one patients had family donors, 62 had unrelated donors. With a 25-month median follow-up, overall survival (OS) at 1, 2, and 4 years was 54%, 40%, and 32%; the respective leukemia-free survival (LFS) was 47%, 37%, and 30%. Patients with PIF showed a 2-year OS of 62.5%. OS was 87% in 17 patients receiving pDLT. One-year cumulative incidence of leukemic death and non-relapse-mortality was 28.7% and 17.2%. In a multivariate analysis, more than 2 courses of prior chemotherapy were the strongest predictor for poor outcome (P = .007; HR = 3.01 [OS]; P = .002; HR = 3.25 [LFS]). These results indicate a high activity of the regimen in refractory AML.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/métodos , Leucemia Mieloide/terapia , Terapia Recuperativa/métodos , Acondicionamiento Pretrasplante/métodos , Enfermedad Aguda , Adolescente , Adulto , Anciano , Terapia Combinada , Femenino , Enfermedad Injerto contra Huésped , Humanos , Leucemia Mieloide/mortalidad , Transfusión de Linfocitos , Masculino , Persona de Mediana Edad , Análisis de Supervivencia , Tasa de Supervivencia , Trasplante HomólogoRESUMEN
The clinical course of chronic lymphocytic leukemia is variable. While some patients have indolent disease, others require aggressive treatment within a short time after diagnosis. Differences in the expression of proteins regulating cell cycle and apoptosis may be responsible for the heterogeneous course of the disease. Recently, protein ZAP 70 [zeta-chain (T-cell receptor) associated protein kinase 70 kDa] has been found to be differentially expressed within two biologic subgroups, characterized by the presence or absence of somatic mutations in specific immunoglobulin heavy-chain variable region genes. In the present work, we analyzed highly purified B-CLL cells from 60 patients for ZAP 70 expression and the expression of cyclin E, bcl-2, bax, and mcl-1 as well as the ratios of bcl-2/bax and mcl-1/bax. The results indicate that cyclin E is expressed significantly higher in ZAP 70-positive as in ZAP 70-negative samples. We did not observe significant differences within the expression of Bcl-2 family member proteins. We conclude that higher cyclin E expression in samples of ZAP 70-positive patients may reflect a larger proliferating compartment in vivo compared to ZAP 70-negative patients and that cyclin E may add prognostic information in this context for patients with B-CLL.
Asunto(s)
Ciclina E/genética , Leucemia Linfocítica Crónica de Células B/genética , Proteínas de Neoplasias/genética , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteína Tirosina Quinasa ZAP-70/metabolismo , Proteína X Asociada a bcl-2/genética , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales , Regulación Neoplásica de la Expresión Génica , Humanos , Leucemia Linfocítica Crónica de Células B/patología , Persona de Mediana Edad , Proteína 1 de la Secuencia de Leucemia de Células Mieloides , Proteínas de Neoplasias/deficiencia , Estadificación de Neoplasias , Proteínas Proto-Oncogénicas c-bcl-2/deficiencia , Células Tumorales Cultivadas , Proteína Tirosina Quinasa ZAP-70/deficiencia , Proteína X Asociada a bcl-2/deficienciaRESUMEN
We report on 232 patients undergoing autologous haematopoietic stem cell transplantation (ASCT) entered into a multicentre, randomised trial comparing the efficacy and tolerability of meropenem (MPM) with that of piperacillin/tazobactam (P/T) as empirical antimicrobial first-line therapy for febrile neutropenia. In 27.6% of patients in the MPM group and 22.4% in the P/T group, therapy was initially supplemented with a glycopeptide for venous catheter infection or bacteraemia because of coagulase-negative staphylococci. Complete response rate after 72 h was 63.8% in the MPM group and 49.6% in the P/T group (P = 0.034). Overall complete response rate after treatment modification was 94.0% in the MPM group and 93.1% in the P/T group. Median time to defervescence was 2 d in the MPM group and 3 d in the P/T group. The most frequently isolated pathogens were Gram-positive cocci. Treatment was well tolerated in both groups. One patient (0.4%) died from infection. Empirical first-line therapy with MPM as well as with P/T is safe and effective in febrile episodes emerging after ASCT. Higher response rates to primary treatment can be achieved with MPM.