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
A randomized inter-group trial comparing more intensive treatment strategies to a common standard arm 3 + 7 (CSA) was conducted in patients with non-M3 AML. Untreated patients ≥ 60 years were allocated to the CSA (n = 132) or to the study group arms (n = 1154) of the AMLCG (TAD/HAM versus HAM/HAM ± G-CSF followed by TAD and maintenance) and the OSHO (intermediate-dose ara-C/mitoxantrone followed by ara-C/mitoxantrone). Median age of the 1147 eligible patients was 69 (range 60-87) years. CR/CRi status at 90 days was not significantly different between the CSA (54% (95%CI: 45-64)) and the study group arms (53% (95%CI: 47-60) and 59% (95%CI: 58-63)). The five-year event-free survival (EFS) probability (primary endpoint) was 6.2% (95%CI: 2.7-14.0) in the CSA, 7.6% (95%CI: 4.5-12.8) in study group A and 11.1% (95%CI: 9.0-13.7) in B. The 5-year OS was 17.2% (95%CI: 11.0-26.9), 17.0% (95%CI: 2.0-23.9), and 19.5% (95%CI: 16.7-22.8) in CSA, study group A and B, respectively. Neither study group differed significantly from the CSA regarding EFS, OS, or relapse-free survival. In multivariate analyses, allocation to the treatment strategy was not significantly associated with the time-to-event endpoints. The evaluation of more intensive treatment strategies did not show clinically relevant outcome differences when compared to CSA.
Asunto(s)
Leucemia Mieloide Aguda , Mitoxantrona , Anciano , Anciano de 80 o más Años , Humanos , Persona de Mediana Edad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Citarabina/uso terapéutico , Daunorrubicina/efectos adversos , Supervivencia sin Enfermedad , Leucemia Mieloide Aguda/tratamiento farmacológico , Mitoxantrona/efectos adversos , Pronóstico , Inducción de RemisiónRESUMEN
OBJECTIVE: A post hoc subgroup analysis of two phase III trials (NCT00416273, NCT00416208) was carried out to investigate the influence of 100/140 and 200 mg/m² melphalan as well as single/double autologous stem cell transplantation (ASCT) on progression-free survival (PFS). Additionally, the effect of bortezomib consolidation on PFS was analyzed. METHODS: Following induction therapy and high-dose melphalan with subsequent ASCT, patients with newly diagnosed multiple myeloma (NDMM) were randomized 1:1 to either four 35-day cycles of bortezomib consolidation (1.6 mg/m² IV on days 1, 8, 15, 22) or observation. RESULTS: Of the 340 patients included in this analysis, 13.5% received 1 × MEL100/140, 22.9% 2 × MEL100/140, 31.2% 1 × MEL200, and 32.4% 2 × MEL200. With higher cumulative melphalan dose, PFS improved (P = .0085). PFS curves of patients treated with 2 × MEL100/140 and 1 × MEL200 were very similar. The superior dose effect of MEL200 over MEL100/140 was non-existent in the bortezomib consolidation arm but pronounced in the observation arm (P = .0015). Similarly, double ASCT was only beneficial in patients without bortezomib consolidation (P = .0569). CONCLUSIONS: Full dose melphalan and double transplantation seem advantageous only as long as patients are not receiving bortezomib consolidation afterwards.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bortezomib/administración & dosificación , Quimioterapia de Consolidación/métodos , Melfalán/administración & dosificación , Mieloma Múltiple/terapia , Anciano , Terapia Combinada , Relación Dosis-Respuesta a Droga , Femenino , Trasplante de Células Madre Hematopoyéticas , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/tratamiento farmacológico , Estudios Retrospectivos , Trasplante AutólogoRESUMEN
Relapse of acute leukemia is a frequent complication with uncertain outcome and poorly defined risk factors. From 1621 patients entered into two prospective clinical trials (AML02; n = 740 and AML04; n = 881), 74.2% reached complete remission (CR) 1 after induction(s) and 59 patients after additional induction ± hematopoietic cell transplantation (HCT). Of the non-refractory patients, 48.4% with a median age of 63 (range 17-85) years relapsed. Relapses occurred within 6 months after CR in 46.5%, between 7 and 18 months in 38.7%, and after 18 months in 14.8% of patients. Relapse treatment resulted in CR2 in 39% of patients depending upon age (54.5% of ≤ 60 and 28.6% of > 60 years), duration of CR1, and treatment of relapse. Overall survival (OS) was 10.9 (7.4-16.2) %, but OS after HCT ± intensive chemotherapy (ICT) was 39.3% (31.8-48.6) at 5 years and not different in younger and older patients. Donor lymphocyte infusion ± chemotherapy and ICT alone resulted only in OS of 15.4% and of 5%, respectively. Independent favorable factors for OS were long CR1 duration, and HCT, while non-monosomal disease was beneficial for OS in elderly patients. Leukemia-free survival [LFS; 24.9 (19.5-31.7) % at 10 years] was affected by similar risk factors. In a competing risk model, the relapse incidence at 5 years was 53.5 ± 3.5% and the non-relapse mortality rate 21.7 ± 2.9%. Lower relapse incidence was observed in patents with HCT, long CR1 duration, and female gender. Risk factors for non-relapse mortality were HCT in younger and type of AML in elderly patients. In conclusion, allogeneic HCT ± IC improved the results in relapsed AML in younger and elderly patients. Increasing CR2 rates and HCT frequency will be the challenge for the next years. Relapse of the disease remains the major problem.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda/terapia , Recurrencia Local de Neoplasia/terapia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Alemania/epidemiología , Humanos , Leucemia Mieloide Aguda/epidemiología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Trasplante Homólogo , Resultado del Tratamiento , Adulto JovenRESUMEN
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
Cancer patients frequently require central venous catheters for therapy and parenteral nutrition and are at high risk of central venous catheter-related infections (CRIs). Moreover, CRIs prolong hospitalization, cause an excess in resource utilization and treatment cost, often delay anti-cancer treatment, and are associated with a significant increase in mortality in cancer patients. We therefore summoned a panel of experts by the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO) and updated our previous guideline on CRIs in cancer patients. After conducting systematic literature searches on PubMed, Medline, and Cochrane databases, video- and meeting-based consensus discussions were held. In the presented guideline, we summarize recommendations on definition, diagnosis, management, and prevention of CRIs in cancer patients including the grading of strength of recommendations and the respective levels of evidence. This guideline supports clinicians and researchers alike in the evidence-based decision-making in the management of CRIs in cancer patients.
Asunto(s)
Infecciones Relacionadas con Catéteres/diagnóstico , Infecciones Relacionadas con Catéteres/terapia , Hematología/normas , Oncología Médica/normas , Guías de Práctica Clínica como Asunto/normas , Sociedades Médicas/normas , Infecciones Relacionadas con Catéteres/epidemiología , Catéteres Venosos Centrales/normas , Enfermedades Transmisibles/diagnóstico , Enfermedades Transmisibles/epidemiología , Enfermedades Transmisibles/terapia , Manejo de la Enfermedad , Alemania/epidemiología , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/epidemiología , Neoplasias Hematológicas/terapia , HumanosRESUMEN
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
This phase 3 trial compared tandem autologous stem cell transplantation (autoSCT) versus autoSCT followed by reduced-intensity conditioning allogeneic stem cell transplantation (auto/alloSCT) in patients with newly diagnosed multiple myeloma (MM) with deletion of (del) chromosome 13q (del13q). The availability/absence of a human leukocyte antigen-matched-related or matched-unrelated donor (MUD) determined the nature of the second SCT. The primary endpoint was progression-free survival (PFS) in the intention-to-treat population (n = 199). Auto/alloSCT was performed in 126 patients; 74 received MUD allografts. After 91 months median follow-up, median PFS with auto/allo versus tandem autoSCT was 34.5 versus 21.8 months (P = 0.003; adjusted hazard ratio 0.55, 95% confidence interval 0.36-0.84). Median overall survival (OS) was 70.2 versus 71.8 months (P = 0.856). Two-year non-relapse mortality with auto/allo versus tandem autoSCT was 14.3% versus 4.1% (P = 0.008). In patients harboring both del13q and del17p, median PFS and OS were 37.5 and 61.5 months with auto/allo (n = 19) versus 6.1 and 23.4 months with tandem autoSCT (n = 6) (P = 0.0002 and 0.032). Our findings suggest that auto/alloSCT significantly extends PFS versus tandem autoSCT in del13q MM, and indicate some survival benefit for first-line alloSCT in high-risk MM.
Asunto(s)
Mieloma Múltiple/genética , Mieloma Múltiple/terapia , Trasplante Homólogo , Adulto , Deleción Cromosómica , Citogenética , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Enfermedad Injerto contra Huésped , Antígenos HLA/química , Humanos , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Acondicionamiento Pretrasplante , Resultado del TratamientoRESUMEN
OBJECTIVE: A post hoc analysis of two phase III trials was carried out to explore the influence of age and treatment factors on the effect of bortezomib consolidation on progression-free survival (PFS) post autologous stem cell transplantation (ASCT). METHODS: Patients with newly diagnosed multiple myeloma were assigned to one of two trials (ClinicalTrials.gov IDs: NCT00416273, NCT00416208), which were conducted in parallel, based on age (18-60 or 61-75 years, respectively). Following induction and ASCT, patients were randomized 1:1 to four 35-day cycles of bortezomib consolidation (1.6 mg/m2 IV on days 1, 8, 15, 22) or observation only. RESULTS: Median PFS with bortezomib consolidation vs observation was 33.6 vs 29.0 months (P = 0.3599) in patients aged 18-60 years (n = 202), and 33.4 vs 26.4 months (P = 0.0073) in patients aged 61-75 years (n = 155), respectively. Bortezomib consolidation post-ASCT appeared to equalize outcomes between older and younger patients who received prior treatment of differing intensity. This suggests that the effect of consolidation may be relative and may depend on the composition and intensity of induction and high-dose therapy. CONCLUSION: Older patients receiving less intensive prior treatment could experience a larger PFS benefit from bortezomib consolidation.
Asunto(s)
Antineoplásicos/uso terapéutico , Bortezomib/uso terapéutico , Trasplante de Células Madre Hematopoyéticas , Mieloma Múltiple/terapia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Bortezomib/administración & dosificación , Bortezomib/efectos adversos , Terapia Combinada , Quimioterapia de Consolidación , Femenino , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/mortalidad , Estadificación de Neoplasias , Pronóstico , Análisis de Supervivencia , Trasplante Autólogo , Resultado del Tratamiento , Adulto JovenRESUMEN
We assessed the safety and efficacy of bortezomib, cyclophosphamide and dexamethasone (VCD) induction therapy in previously untreated multiple myeloma patients. A total of 414 patients received three 21-day cycles of VCD prior to autologous stem-cell transplantation (ASCT). Most common grade ≥3 adverse events were leucopenia (31·4%) and thrombocytopenia (6·8%). The overall response rate (ORR) by investigator-based assessment was 85·4%. Most patients (74%) underwent successful central laboratory-based molecular cytogenetic analysis. No clinically relevant differences in ORR post-induction were seen between patients with or without high-risk cytogenetic abnormalities (86·2% vs. 84·3%). Further follow-up data are available for 113 patients receiving ASCT who were included in a prospective consolidation trial (median follow-up, 55·5 months); median progression-free survival (PFS) was 35·3 months and median overall survival (OS) was not reached. In patients with high-risk versus standard-risk cytogenetics, median PFS was 19·9 vs. 43·6 months (P < 0·0001), and median OS was 54·7 months versus not reached (P = 0·0022). VCD is an effective and tolerable induction regimen; results suggest that VCD induces high response rates independently of cytogenetic risk status, but after long-term follow-up, cytogenetic high risk is associated with markedly reduced PFS and OS post-ASCT.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioterapia de Inducción/métodos , Mieloma Múltiple/tratamiento farmacológico , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bortezomib/administración & dosificación , Quimioterapia de Consolidación , Ciclofosfamida/administración & dosificación , Citogenética , Dexametasona/administración & dosificación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/mortalidad , Medición de Riesgo/métodos , Trasplante de Células Madre , Análisis de Supervivencia , Trasplante Autólogo , Adulto JovenRESUMEN
BACKGROUND: Community acquired viruses (CRVs) may cause severe disease in cancer patients. Thus, efforts should be made to diagnose CRV rapidly and manage CRV infections accordingly. METHODS: A panel of 18 clinicians from the Infectious Diseases Working Party of the German Society for Haematology and Medical Oncology have convened to assess the available literature and provide recommendations on the management of CRV infections including influenza, respiratory syncytial virus, parainfluenza virus, human metapneumovirus and adenovirus. RESULTS: CRV infections in cancer patients may lead to pneumonia in approximately 30% of the cases, with an associated mortality of around 25%. For diagnosis of a CRV infection, combined nasal/throat swabs or washes/aspirates give the best results and nucleic acid amplification based-techniques (NAT) should be used to detect the pathogen. Hand hygiene, contact isolation and face masks have been shown to be of benefit as general infection management. Causal treatment can be given for influenza, using a neuraminidase inhibitor, and respiratory syncytial virus, using ribavirin in addition to intravenous immunoglobulins. Ribavirin has also been used to treat parainfluenza virus and human metapneumovirus, but data are inconclusive in this setting. Cidofovir is used to treat adenovirus pneumonitis. CONCLUSIONS: CRV infections may pose a vital threat to patients with underlying malignancy. This guideline provides information on diagnosis and treatment to improve the outcome.
Asunto(s)
Antivirales/uso terapéutico , Infecciones Comunitarias Adquiridas/terapia , Inmunoglobulinas Intravenosas/uso terapéutico , Factores Inmunológicos/uso terapéutico , Neoplasias/epidemiología , Infecciones del Sistema Respiratorio/terapia , Virosis/terapia , Infecciones por Adenovirus Humanos/diagnóstico , Infecciones por Adenovirus Humanos/epidemiología , Infecciones por Adenovirus Humanos/terapia , Cidofovir , Infecciones Comunitarias Adquiridas/diagnóstico , Infecciones Comunitarias Adquiridas/epidemiología , Citosina/análogos & derivados , Citosina/uso terapéutico , Alemania , Higiene de las Manos , Humanos , Gripe Humana/diagnóstico , Gripe Humana/epidemiología , Gripe Humana/terapia , Pulmón/diagnóstico por imagen , Máscaras , Oncología Médica , Metapneumovirus , Neuraminidasa/antagonistas & inhibidores , Técnicas de Amplificación de Ácido Nucleico , Organofosfonatos/uso terapéutico , Oseltamivir/uso terapéutico , Infecciones por Paramyxoviridae/diagnóstico , Infecciones por Paramyxoviridae/epidemiología , Infecciones por Paramyxoviridae/terapia , Aislamiento de Pacientes , Neumonía Viral/diagnóstico , Neumonía Viral/epidemiología , Neumonía Viral/terapia , Infecciones por Virus Sincitial Respiratorio/diagnóstico , Infecciones por Virus Sincitial Respiratorio/epidemiología , Infecciones por Virus Sincitial Respiratorio/terapia , Infecciones del Sistema Respiratorio/diagnóstico , Infecciones del Sistema Respiratorio/epidemiología , Ribavirina/uso terapéutico , Tomografía Computarizada por Rayos X , Virosis/diagnóstico , Virosis/epidemiologíaRESUMEN
Autologous transplantation is controversial for older patients with multiple myeloma. The role of age-adjusted high-dose melphalan and the impact of induction chemotherapy cycles is still unclear. A total of 434 patients aged 60-70 years were randomly assigned to 4 cycles of standard anthracycline-based induction chemotherapy or no induction. For all patients, double autologous transplantation after melphalan 140 mg/m2 (MEL140) was planned. The primary end point was progression-free survival. Of 420 eligible patients, 85% received a first transplant and 69% completed double transplantation. Treatment duration was short with a median of 7.7 months with induction chemotherapy cycles and 4.6 months without induction. On an intention-to-treat basis, median progression-free survival with induction chemotherapy cycles (207 patients) was 21.4 months versus 20.0 months with no induction cycles (213 patients) (hazard ratio 1.04, 95% confidence interval 0.84-1.28; P=0.36). Per protocol, progression-free survival was 23.7 months versus 23.0 months (P=0.28). Patients aged 65 years or over (55%) did not have an inferior outcome. Patients with low-risk cytogenetics [absence of del17p13, t(4;14) and 1q21 gains] showed a favorable overall survival and included the patients with sustained first remission. MEL140 was associated with a low rate of severe mucositis (10%) and treatment-related deaths (1%). Based on hazard ratio, the short treatment arm consisting of mobilization chemotherapy and tandem MEL140 achieved 96% of the progression-free survival, demonstrating its value as an independent component of therapy in older patients with multiple myeloma who are considered fit for autologous transplantation. (clinicaltrials.gov identifier: 02288741).
Asunto(s)
Mieloma Múltiple/terapia , Trasplante de Células Madre/métodos , Anciano , Citogenética , Supervivencia sin Enfermedad , Femenino , Movilización de Célula Madre Hematopoyética/métodos , Humanos , Quimioterapia de Inducción/métodos , Masculino , Melfalán/administración & dosificación , Persona de Mediana Edad , Mucositis/inducido químicamente , Mieloma Múltiple/complicaciones , Mieloma Múltiple/mortalidad , Trasplante de Células Madre/mortalidad , Trasplante Autólogo , Resultado del TratamientoRESUMEN
BACKGROUND: High-dose methotrexate-based chemotherapy is standard for primary CNS lymphoma, but most patients relapse. High-dose chemotherapy with autologous stem cell transplantation (HCT-ASCT) is supposed to overcome the blood-brain barrier and eliminate residual disease in the CNS. We aimed to investigate the safety and efficacy of HCT-ASCT in patients with newly diagnosed primary CNS lymphoma. METHODS: In this prospective, single-arm, phase 2 trial, we recruited patients aged 18-65 years with newly diagnosed primary CNS lymphoma and immunocompetence, with no limitation on clinical performance status, from 15 hospitals in Germany. Patients received five courses of intravenous rituximab 375 mg/m(2) (7 days before first high-dose methotrexate course and then every 10 days) and four courses of intravenous high-dose methotrexate 8000 mg/m(2) (every 10 days) and then two courses of intravenous rituximab 375 mg/m(2) (day 1), cytarabine 3 g/m(2) (days 2 and 3), and thiotepa 40 mg/m(2) (day 3). 3 weeks after the last course, patients commenced intravenous HCT-ASCT (rituximab 375 mg/m(2) [day 1], carmustine 400 mg/m(2) [day 2], thiotepa 2â×â5 mg/kg [days 3 and 4], and infusion of stem cells [day 7]), irrespective of response status after induction. We restricted radiotherapy to patients without complete response after HCT-ASCT. The primary endpoint was complete response at day 30 after HCT-ASCT in all registered eligible patients who received at least 1 day of study treatment. This trial is registered at ClinicalTrials.gov, number NCT00647049. FINDINGS: Between Jan 18, 2007, and May 23, 2011, we recruited 81 patients, of whom two (2%) were excluded, therefore we included 79 (98%) patients in the analysis. All patients started induction treatment; 73 (92%) commenced HCT-ASCT. 61 (77·2% [95% CI 66·1-86·6]) patients achieved a complete response. During induction treatment, the most common grade 3 toxicity was anaemia (37 [47%]) and the most common grade 4 toxicity was thrombocytopenia (50 [63%]). During HCT-ASCT, the most common grade 3 toxicity was fever (50 [68%] of 73) and the most common grade 4 toxicity was leucopenia (68 [93%] of 73). We recorded four (5%) treatment-related deaths (three [4%] during induction and one [1%] 4 weeks after HCT-ASCT). INTERPRETATION: HCT-ASCT with thiotepa and carmustine is an effective treatment option in young patients with newly diagnosed primary CNS lymphoma, but further comparative studies are needed. FUNDING: University Hospital Freiburg and Amgen.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Sistema Nervioso Central/terapia , Trasplante de Células Madre Hematopoyéticas , Linfoma no Hodgkin/terapia , Adolescente , Adulto , Anciano , Carmustina/administración & dosificación , Neoplasias del Sistema Nervioso Central/diagnóstico , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Linfoma no Hodgkin/diagnóstico , Masculino , Metotrexato/administración & dosificación , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Rituximab/administración & dosificación , Tasa de Supervivencia , Tiotepa/administración & dosificación , Trasplante Autólogo , Adulto JovenRESUMEN
This report describes the clinical course over almost one decade of a male patient presenting with immune-mediated pure autonomic neuropathy resembling a distinct variant of chronic dysimmune polyneuropathies. We suppose autoantibodies directed against epitopes on autonomic axons or neurons causative for the symptoms.
Asunto(s)
Enfermedades del Sistema Nervioso Autónomo/fisiopatología , Enfermedades Autoinmunes Desmielinizantes SNC/fisiopatología , Polineuropatías/fisiopatología , Enfermedades del Sistema Nervioso Autónomo/patología , Vasos Sanguíneos/patología , Enfermedades Autoinmunes Desmielinizantes SNC/patología , Progresión de la Enfermedad , Respuesta Galvánica de la Piel , Frecuencia Cardíaca , Humanos , Masculino , Persona de Mediana Edad , Polineuropatías/patología , Pruebas de Mesa InclinadaRESUMEN
Philadelphia-negative myeloproliferative neoplasms (Ph-negative MPN) comprise a heterogeneous group of chronic hematologic malignancies. The quality of life, morbidity, and mortality of patients with MPN are primarily affected by disease-related symptoms, thromboembolic and hemorrhagic complications, and progression to myelofibrosis and acute leukemia. Major bleeding represents a common and important complication in MPN, and the incidence of such bleeding events will become even more relevant in the future due to the increasing disease prevalence and survival of MPN patients. This review discusses the causes, differential diagnoses, prevention, and management of bleeding episodes in patients with MPN, aiming at defining updated standards of care in these often challenging situations.
Asunto(s)
Hemorragia/etiología , Técnicas Hemostáticas , Trastornos Mieloproliferativos/complicaciones , Anticoagulantes/efectos adversos , Anticoagulantes/uso terapéutico , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Factores de Coagulación Sanguínea/uso terapéutico , Pérdida de Sangre Quirúrgica/prevención & control , Transfusión Sanguínea , Vasos Sanguíneos/efectos de los fármacos , Vasos Sanguíneos/patología , Ensayos Clínicos como Asunto , Contraindicaciones , Desamino Arginina Vasopresina/uso terapéutico , Manejo de la Enfermedad , Procedimientos Quirúrgicos Electivos , Hemorragia/diagnóstico , Hemorragia/prevención & control , Hemorragia/terapia , Humanos , Leucemia Mieloide Crónica Atípica BCR-ABL Negativa/complicaciones , Leucemia Mieloide Crónica Atípica BCR-ABL Negativa/tratamiento farmacológico , Leucemia Mieloide Crónica Atípica BCR-ABL Negativa/genética , Hígado/fisiopatología , Estudios Multicéntricos como Asunto , Trastornos Mieloproliferativos/tratamiento farmacológico , Trastornos Mieloproliferativos/genética , Inhibidores de Agregación Plaquetaria/efectos adversos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Pruebas de Función Plaquetaria , Transfusión de Plaquetas , Hemorragia Posoperatoria/etiología , Hemorragia Posoperatoria/prevención & control , Hemorragia Posoperatoria/terapia , Trombofilia/tratamiento farmacológico , Trombofilia/etiología , Ácido Tranexámico/uso terapéutico , Enfermedades de von Willebrand/etiología , Factor de von Willebrand/análisisRESUMEN
PURPOSE: Positron emission tomography (PET) after chemotherapy can guide consolidating radiotherapy in advanced-stage Hodgkin lymphoma (HL). This analysis aims to improve outcome prediction by integrating additional criteria derived by computed tomography (CT). PATIENTS AND METHODS: The analysis set consisted of 739 patients with residues≥2.5 cm after chemotherapy from a total of 2,126 patients treated in the HD15 trial (HD15 for advanced stage Hodgkin's disease: Quality assurance protocol for reduction of toxicity and the prognostic relevance of fluorodeoxyglucose-positron-emission tomography [FDG-PET] in the first-line treatment of advanced-stage Hodgkin's disease) performed by the German Hodgkin Study Group. A central panel performed image analysis and interpretation of CT scans before and after chemotherapy as well as PET scans after chemotherapy. Prognosis was evaluated by using progression-free survival (PFS); groups were compared with the log-rank test. Potential prognostic factors were investigated by using receiver operating characteristic analysis and logistic regression. RESULTS: In all, 548 (74%) of 739 patients had PET-negative residues after chemotherapy; these patients did not receive additional radiotherapy and showed a 4-year PFS of 91.5%. The 191 PET-positive patients (26%) receiving additional radiotherapy had a 4-year PFS of 86.1% (P=.022). CT alone did not allow further separation of patients in partial remission by risk of recurrence (P=.9). In the subgroup of the 54 PET-positive patients with a relative reduction of less than 40%, the risk of progression or relapse within the first year was 23.1% compared with 5.3% for patients with a larger reduction (difference, 17.9%; 95% CI, 5.8% to 30%). CONCLUSION: Patients with HL who have PET-positive residual disease after chemotherapy and poor tumor shrinkage are at high risk of progression or relapse.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Enfermedad de Hodgkin/diagnóstico , Enfermedad de Hodgkin/tratamiento farmacológico , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Bleomicina/administración & dosificación , Estudios de Cohortes , Ciclofosfamida/administración & dosificación , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Etopósido/administración & dosificación , Femenino , Fluorodesoxiglucosa F18 , Enfermedad de Hodgkin/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Imagen Multimodal/métodos , Tomografía de Emisión de Positrones/métodos , Prednisona/administración & dosificación , Procarbazina/administración & dosificación , Pronóstico , Estudios Prospectivos , Radiofármacos , Tomografía Computarizada por Rayos X/métodos , Resultado del Tratamiento , Carga Tumoral , Vincristina/administración & dosificación , Adulto JovenRESUMEN
The Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO) here presents its updated recommendations for the treatment of documented fungal infections. Invasive fungal infections are a main cause of morbidity and mortality in cancer patients undergoing intensive chemotherapy regimens. In recent years, new antifungal agents have been licensed, and agents already approved have been studied in new indications. The choice of the most appropriate antifungal treatment depends on the fungal species suspected or identified, the patient's risk factors (e.g., length and depth of neutropenia), and the expected side effects. This guideline reviews the clinical studies that served as a basis for the following recommendations. All recommendations including the levels of evidence are summarized in tables to give the reader rapid access to the information.
Asunto(s)
Antifúngicos/uso terapéutico , Micosis/tratamiento farmacológico , Neoplasias/complicaciones , Anfotericina B/administración & dosificación , Anfotericina B/efectos adversos , Anfotericina B/uso terapéutico , Antifúngicos/administración & dosificación , Antifúngicos/efectos adversos , Candidiasis Invasiva/tratamiento farmacológico , Candidiasis Invasiva/etiología , Infecciones Relacionadas con Catéteres/tratamiento farmacológico , Infecciones Relacionadas con Catéteres/prevención & control , Neutropenia Febril Inducida por Quimioterapia/complicaciones , Ensayos Clínicos como Asunto , Terapia Combinada , Monitoreo de Drogas , Quimioterapia Combinada , Equinocandinas/administración & dosificación , Equinocandinas/efectos adversos , Equinocandinas/uso terapéutico , Fungemia/tratamiento farmacológico , Fungemia/prevención & control , Humanos , Huésped Inmunocomprometido , Inmunoterapia , Aspergilosis Pulmonar Invasiva/tratamiento farmacológico , Aspergilosis Pulmonar Invasiva/etiología , Aspergilosis Pulmonar Invasiva/cirugía , Micosis/etiología , Micosis/cirugía , Micosis/terapia , Terapia Recuperativa , Triazoles/administración & dosificación , Triazoles/efectos adversos , Triazoles/uso terapéuticoRESUMEN
OBJECTIVES: Diagnosing invasive pulmonary aspergillosis (IPA) remains a challenge in patients with hematological malignancies. The clinical significance of testing bronchoalveolar lavage (BAL) samples both with polymerase chain reaction (PCR) and Aspergillus galactomannan ELISA (GM) is unclear, and the BAL cutoff for GM has not been clearly evaluated yet. METHODS: Using a validated nested PCR assay and a GM ELISA, we prospectively examined BAL samples from 87 hematological patients at high risk of IPA. Of 76 (87%) evaluable patients, 29 patients had proven or probable disease. RESULTS: The receiver operating characteristic (ROC) analysis of GM optical density (OD) cutoff levels yielded a BAL OD of 0.5 to be optimal. We identified 29 probable or proven cases based on this OD. Sensitivity and specificity for BAL GM were 0.79 (95% CI, 0.62-0.9) and 0.96 (95% CI, 0.86-0.99), respectively. For BAL PCR, sensitivity and specificity were 0.59 (95% CI, 0.41-0.75) and 0.87 (95% CI, 0.75-0.94), respectively. Combining BAL GM and PCR for diagnosis showed a sensitivity and specificity rate of 0.55 (95% CI, 0.38-0.72) and 1.0 (95% CI, 0.93-1.0), respectively, if positivity was defined by positive results for both tests. If either positive BAL GM or positive BAL PCR results defined test positivity, the sensitivity was 0.83 (95% CI, 0.65-0.92), and the specificity was 0.83 (95% CI, 0.70-0.91) CONCLUSIONS: In terms of optimal sensitivity and specificity, a GM OD cutoff of 0.5 was determined for BAL samples. Positivity for both GM and Aspergillus PCR in BAL makes a pulmonary aspergillosis highly likely.