Listeria monocytogenes Infections in Hematopoietic Cell Transplantation Recipients: Clinical Manifestations and Risk Factors. A Multinational Retrospective Case-Control Study from the Infectious Diseases Working Party of the European Society for Blood and Marrow Transplantation.

Listeriosis is rare after hematopoietic stem cell transplantation (HCT). Little is known about listeriosis in this population. In this retrospective international case-control study, we evaluated 41 listeriosis episodes occurring between 2000 and 2021 in HCT recipients (111 transplant centers in 30 countries) and assessed risk factors for listeriosis by comparisons with matched controls. The 41 listeriosis episodes (all due to Listeria monocytogenes [LM]) occurred in 30 allogeneic (allo)-HCT recipients and 11 autologous (auto)-HCT recipients at a median of 6.2 months (interquartile range [IQR], 1.6 to 19.3 months) post-HCT. The estimated incidence was 49.8/100,000 allo-HCT recipients and 13.7/100,000 auto-HCT recipients. The most common manifestations in our cohort were fever (n = 39; 95%), headache (n = 9; 22%), diarrhea, and impaired consciousness (n = 8 each; 20%). Four patients (10%) presented with septic shock, and 19 of 38 (50%) were severely lymphocytopenic. Thirty-seven patients (90%) had LM bacteremia. Eleven patients (27%) had neurolisteriosis, of whom 4 presented with nonspecific signs and 5 had normal brain imaging findings. Cerebrospinal fluid analysis revealed high protein and pleocytosis (mainly neutrophilic). Three-month mortality was 17% overall (n = 7), including 27% (n = 3 of 11) in patients with neurolisteriosis and 13% (n = 4 of 30) in those without neurolisteriosis. In the multivariate analysis comparing cases with 74 controls, non-first HCT (odds ratio [OR], 5.84; 95% confidence interval [CI], 1.10 to 30.82; P = .038); and lymphocytopenia <500 cells/mm3 (OR, 7.54; 95% CI, 1.50 to 37.83; P = .014) were significantly associated with listeriosis. There were no statistically significant differences in background characteristics, immunosuppression, and cotrimoxazole prophylaxis between cases and controls. HCT recipients are at increased risk for listeriosis compared to the general population. Listeriosis cause severe disease with septic shock and mortality. Neurolisteriosis can present with nonspecific signs and normal imaging. Lymphocytopenia and non-first HCT are associated with an increased risk of listeriosis, and cotrimoxazole was not protective.

Pneumocystis Pneumonia After Allogeneic Hematopoietic Cell Transplantation: A Case-Control Study on Epidemiology and Risk Factors on Behalf of the Infectious Diseases Working Party of the European Society for Blood and Marrow Transplantation.

Pneumocystis pneumonia (PCP) is a life-threatening complication after allogeneic hematopoietic cell transplantation (allo-HCT). However, allo-HCT procedures have evolved toward older patients, unrelated donors, and reduced-intensity conditioning, possibly modifying the risks. Polymerase chain reaction (PCR), widely used nowadays, is more sensitive than microscopy diagnostic methods. This study aimed to assess the factors associated with PCP in allo-HCT recipients within 2 years of HCT and managed according to current procedures. This multicenter, nested case-control study included PCP cases diagnosed by PCR, cytology, or immunofluorescence on bronchoalveolar lavage fluid between 2016 and 2018. Two controls per case were selected from the ProMISe registry and matched for the center, transplant date, and underlying disease. Fifty-two cases and 104 controls were included among the 5452 patients who underwent allo-HCT in the participating centers. PCP occurred at a median of 11.5 months after transplantation. The mortality rate was 24% on day 30 after the PCP diagnosis and 37% on day 90. The clinical presentation and mortality rates of the 24 patients diagnosed using only PCR were not different from those diagnosed with microscopy methods. Our study demonstrates a substantial incidence of, and mortality from, PCP, after allogeneic HCT despite well-established prophylactic approaches. In our experience, PCP nowadays occurs later after transplant than previously reported, justifying the prolongation of prophylaxis after six months in many cases. Allo-HCT recipients diagnosed with PCR as the only PCP marker should benefit from specific treatment as for other patients.

Influence of invasive aspergillosis during acute leukaemia treatment on survival after allogeneic stem cell transplantation: a prospective study of the EBMT Infectious Diseases Working Party.

Background: Infections are the main reason for mortality during acute leukaemia treatment and invasive aspergillosis (IA) is a major concern. Allogeneic stem cell transplantation (alloSCT) is a standard therapy and often is the only live-saving procedure in leukaemia patients. The profound immunodeficiency occurring after alloSCT led to high IA-associated mortality in the past. Therefore, patients with IA were historically considered transplant-ineligible. Recently, there has been improvement of anti-fungal management including novel anti-fungal agents. As a result, more leukaemia patients with IA are undergoing alloSCT. Outcome has not been prospectively assessed. Methods: We performed a prospective study in acute leukaemia patients undergoing alloSCT to analyse the impact of a prior history of probable or proven IA (pre-SCT IA). The primary endpoint was 1-year non-relapse mortality (NRM). Relapse free survival and overall survival were analysed as secondary endpoints. Findings: 1439 patients were included between 2016 and 2021. The incidence of probable or proven pre-SCT IA was 6.0% (n = 87). The cumulative incidence of 1-year NRM was 17.3% (95% CI 10.2-26.0) and 11.2% (9.6-13.0) for patients with and without pre-SCT IA. In multivariate analyses the hazard ratio (HR) for 1-year NRM was 2.1 (1.2-3.6; p = 0.009) for patients with pre-SCT IA. One-year relapse-free survival was inferior in patients with pre-SCT IA (59.4% [48.3-68.9] vs. 70.4 [67.9-72.8]; multivariate HR 1.5 [1.1-2.1]; p = 0.02). Consequently, 1-year overall survival was lower in patients with pre-SCT IA: (68.8% [57.8-77.4] vs. 79.0% [76.7-81.1]; multivariate HR 1.7 [1.1-2.5]; p = 0.01). Interpretation: Pre-SCT IA remains to be significantly associated with impaired alloSCT outcome. On the other hand, more than two thirds of patients with pre-SCT IA were alive at one year after alloSCT. IA is not anymore an absolute contraindication for alloSCT because the majority of patients with IA who undergo alloSCT benefit from this procedure. Funding: There was no external funding source for this study.

Impact of the COVID-19 pandemic on the diagnosis and treatment of onco-hematologic patients: a discussion paper / Impacto de la pandemia de COVID-19 en el diagnóstico y tratamiento de los pacientes onco-hematológicos: un documento de opinión

We do not know the precise figure for solid organ tumors diagnosed each year in Spain and it is therefore difficult to calculate whether there has been a decrease in cancer diagnoses as a consequence of the pandemic. Some indirect data suggest that the pandemic has worsened the stage at which some non-hematological neoplasms are diagnosed. Despite the lack of robust evidence, oncology patients seem more likely to have a poor outcome when they contract COVID-19. The antibody response to infection in cancer patients will be fundamentally conditioned by the type of neoplasia present, the treatment received and the time of its administration.In patients with hematological malignancies, the incidence of infection is probably similar or lower than in the general population, due to the better protective measures adopted by the patients and their environment. The severity and mortality of COVID-19 in patients with hematologic malignancies is clearly higher than the general population. Since the immune response to vaccination in hematologic patients is generally worse than in comparable populations, alternative methods of prevention must be established in these patients, as well as actions for earlier diagnosis and treatment.Campaigns for the early diagnosis of malignant neoplasms must be urgently resumed, post-COVID manifestations should be monitored, collaboration with patient associations is indisputable and it is urgent to draw the right conclusions to improve our preparedness to fight against possible future catastrophes. (AU)

No conocemos con precisión la cifra nacional de tumores sólidos diagnosticados en España anualmente y por tanto se hace difícil calcular si ha habido una disminución de diagnósticos de cáncer como consecuencia de la pandemia. Algunos datos indirectos permiten sospechar que la pandemia ha empeorado el estadio en que se diagnostican algunas neoplasias no hematológicas. A pesar de no existir una evidencia robusta, los pacientes oncológicos presentan una mayor tendencia a tener una mala evolución cuando contraen COVID-19. La respuesta de anticuerpos frente a la infección en pacientes con cáncer va a estar condicionada fundamentalmente por el tipo de neoplasia presente, el tratamiento recibido y el momento de su administración.En pacientes con hemopatías malignas la incidencia de infección es probablemente similar o inferior a la de la población general, debido a las mejores medidas de protección adoptadas por los pacientes y su entorno. La gravedad y letalidad de la COVID-19 en pacientes con hemopatías malignas es claramente más elevada que en la población general. Dado que la respuesta inmune a la vacunación es peor que en poblaciones comparables, hay que establecer métodos alternativos de prevención en estos pacientes, así como planes de diagnóstico y tratamiento precoces.Hay que retomar las campañas de diagnóstico precoz de neoplasias malignas con urgencia, vigilar las manifestaciones post-COVID, colaborar con las asociaciones de pacientes y hacer planes urgentes para hacer frente con más eficiencia a potenciales catástrofes futuras. (AU)

[Thrombosis with Thrombocytopenia Syndrome following adenovirus vector-based vaccines to prevent COVID-19: epidemiology and clinical presentation in Spain]. / Síndrome de Trombosis con Trombocitopenia asociado a vacunas de adenovirus frente a la COVID-19: epidemiología y presentación clínica de la serie española.

BACKGROUND: We describe the epidemiological and clinical characteristics of thrombosis with thrombocytopenia syndrome (TTS) cases reported in Spain. METHODS: We included all venous or arterial thrombosis with thrombocytopenia following adenovirus vector-based vaccines (AstraZeneca or Janssen) to prevent COVID-19 disease between February 1st and September 26th, 2021. We describe the crude rate and the standardized morbidity ratio. We assessed the predictors of mortality. RESULTS: Sixty-one cases were reported and 45 fulfilled eligibility criteria, 82% women. The crude TTS rate was 4/1,000,000 doses and 14-15/1,000,000 doses between 30-49 years. The number of observed cases of cerebral venous thrombosis was 6-18 higher than the expected in patients younger than 49 years. Symptoms started 10 (interquartile range (IQR): 7-14) days after vaccination. Eighty percent (95% confidence interval (CI): 65-90%) had thrombocytopenia at the time of the emergency department visit, and 65% (95% CI: 49-78%) had D-dimer >2000 ng/mL. Patients had multiple location thrombosis in 36% and fatal outcome in 24% cases. A platelet nadir <50,000 /µL (odds ratio (OR): 7.4; CI 95%: 1.2-47.5) and intracranial hemorrhage (OR: 7.9; IC95%: 1.3-47.0) were associated with fatal outcome. CONCLUSION: TTS must be suspected in patients with symptoms 10 days after vaccination and thrombocytopenia and/or D-dimer increase.

Estudio de resistencias de citomegalovirus en pacientes receptores de trasplante alogénico de progenitores hematopoyéticos / Study of cytomegalovirus resistance in allogeneic hematopoietic cell transplant recipients

INTRODUCCIÓN: El citomegalovirus (CMV) es el patógeno oportunista más importante asociado al trasplante. El objetivo de este trabajo fue la caracterización de mutaciones de resistencia de CMV en pacientes receptores de trasplante alogénico de progenitores hematopoyéticos (alo-TPH) y el estudio de factores asociados. MÉTODOS: Se llevó a cabo un estudio retrospectivo de una cohorte de pacientes receptores de alo-TPH con reactivaciones postrasplante de CMV con cargas virales (CV) estables o en aumento, a pesar de un adecuado tratamiento antiviral al menos durante 2semanas. Se realizó el estudio de mutaciones de resistencia de los genes UL97 y UL54 mediante secuenciación Sanger. RESULTADOS: La infección refractaria de CMV de nuestro grupo de pacientes alo-TPH se correspondió con una tasa de infección por virus resistente del 21,43% (3 de 14 pacientes). Todos los pacientes con mutaciones de resistencia presentaron múltiples episodios de reactivación (p-valor 0,01). Las mutaciones encontradas fueron A594V y H520Q en el gen UL97 que confieren resistencia de alto grado a ganciclovir (GCV). Uno de los 3 casos con resistencia antiviral, se documentó con una CV baja (< 1.000 copias/ml) y tras corto tratamiento acumulado de GCV (41 días). CONCLUSIÓN: La mayor parte de los fracasos en el tratamiento del CMV se debió posiblemente a resistencia clínica; la falta de respuesta satisfactoria al tratamiento antiviral no siempre se acompaña de resistencia virológica. No obstante, la aparición de resistencias puede ocurrir de forma temprana tras el inicio del tratamiento anticipado y con CV por debajo de 1.000 copias/ml. El número de episodios de reactivación fue mayor entre los pacientes que se demostró resistencia virológica frente a los que no

INTRODUCTION: Cytomegalovirus (CMV) is the most important opportunistic pathogen associated with transplant. The objective of this study was the characterization of CMV resistance mutations in allogeneic haematopoietic cell transplant recipients (allo-TPH) and the study of associated factors. METHODS: A retrospective study of a cohort of allo-TPH recipients with post-transplant CMV reactivations with stable or increasing viral loads (CV), despite adequate antiviral treatment for at least 2weeks. The study of resistance mutations of the UL97 and UL54 genes was carried out by Sanger sequencing. RESULTS: Refractory CMV infection in our group of allo-TPH patients corresponded with a 21.43% rate of resistant virus infection (3 of 14 patients). All patients with resistance mutations had multiple reactivation episodes (P-value .01). The mutations found were A594V and H520Q in the UL97 gene that confers high-grade resistance to ganciclovir (GCV). One of the 3 cases with antiviral resistance was documented with a low VL (< 1000 copies/ml) and short accumulated GCV treatment (41 days). CONCLUSION: Most of the failures in the treatment of CMV were possibly due to clinical resistance; the lack of satisfactory response to antiviral treatment is not always accompanied by virological resistance. However, the appearance of resistances can occur early after the start of the treatment and with VL below 1000 copies / ml. The number of episodes of reactivation was higher among patients with virological resistance than those who did not

Executive summary of the consensus document of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC), the Spanish Network for Research in Infectious Diseases (REIPI) and the Spanish Society of Haematology and Haemotherapy (SEHH) on the management of febrile neutropenia in patients with hematological malignancies / Resumen ejecutivo del documento de la Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica (SEIMC), la Red Española de Investigación en Patología Infecciosa (REIPI) y la Sociedad Española de Hematología y Hemoterapia (SEHH) sobre el manejo de la neutropenia febril en el paciente hematológico

Febrile neutropenia is a very common complication in patients with hematological malignancies receiving chemotherapy, and is associated with high morbidity and mortality. Infections caused by multidrug-resistant bacteria have become a therapeutic challenge in this high-risk patient population, since inadequate initial empirical treatment can seriously compromise prognosis. However, reducing antimicrobial exposure is one of the most significant cornerstones in the fight against resistance. The objective of these new guidelines is to update recommendations for the initial management of hematological patients who develop febrile neutropenia in this scenario of multidrug resistance. The two participating Societies (the Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica [Spanish Society of Infectious Diseases and Clinical Microbiology] and the Sociedad Española de Hematología y Hemoterapia [Spanish Society of Haematology and Haemotherapy]), designated a panel of experts in the field to provide evidence-based recommendations in response to common clinical questions. This document is primarily focused on bacterial infections. Other aspects related to opportunistic infections, such as those caused by fungi or other microorganisms, especially in hematopoietic stem cell transplantation, are also touched upon

La neutropenia febril es una complicación muy frecuente en los pacientes hematológicos que reciben tratamiento quimioterápico, y se asocia a una importante morbimortalidad. Las infecciones por bacterias multirresistentes se han convertido en un reto terapéutico en esta población de pacientes de alto riesgo, en los que un tratamiento empírico inicial inadecuado puede comprometer gravemente su pronóstico. Sin embargo, reducir la exposición a los antimicrobianos es uno de los pilares más importantes en la lucha frente a las resistencias. El objetivo de esta nueva guía es actualizar las recomendaciones sobre el manejo inicial del paciente hematológico que desarrolla neutropenia febril en el escenario actual de multirresistencia. Para la elaboración de este documento, las 2 sociedades implicadas (la Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica y la Sociedad Española de Hematología y Hemoterapia) designaron expertos en este tema, quienes han realizado recomendaciones basadas en la evidencia, en respuesta a cuestiones clínicas habituales. Este documento está enfocado básicamente a la infección bacteriana. Otros aspectos relacionados con las infecciones oportunistas, como las producidas por hongos u otros microorganismos, sobre todo en el seno del trasplante de progenitores hematopoyéticos, se abordan de forma tangencial

Posicionamiento y actitudes de manejo sobre la profilaxis antifúngica en el paciente hematológico (proyecto PROMIC) / Consensus opinion on antifungal prophylaxis in haematologic patients: Results of the PROMIC project

Introducción. La enfermedad fúngica invasora (EFI) es una importante causa de morbimortalidad en pacientes hematológicos. La profilaxis antifúngica (PAF) está indicada en muchos episodios de este grupo de pacientes. El objetivo de este trabajo fue alcanzar un consenso sobre el abordaje profiláctico de las EFI en el paciente hematológico con el fin de optimizar su manejo. Métodos. Un comité de expertos en hematología y enfermedades infecciosas planteó un cuestionario de 79 ítems con aspectos controvertidos sobre la profilaxis antifúngica en el paciente hematológico. El cuestionario fue evaluado en dos rondas por un panel de expertos siguiendo una metodología Delphi modificada. Resultados. El cuestionario fue respondido por 44 expertos en hematología y enfermedades infecciosas. Tras dos rondas de evaluación se consensuaron 48 ítems en el acuerdo (60,7%) y 19 en el desacuerdo (24%) por lo que hubo consenso en 67 de los 79 ítems planteados (84,8%). Se consensuaron los perfiles de pacientes candidatos a profilaxis y se dilucidaron cuestiones relacionadas con indicaciones, mecanismos de acción, espectro de actividad, toxicidad e interacciones de los antifúngicos. Se analizó particularmente la utilidad de micafungina como profilaxis de EFI. Se consensuó que micafungina es un antifúngico a considerar en este contexto. Puede presentar ventajas sobre otros antifúngicos por su seguridad y menor potencial de interacciones. Conclusiones. Se encontró un alto nivel de consenso en el manejo de la profilaxis de la EFI en el paciente hematológico. Este consenso ofrece indicaciones prácticas sobre su manejo óptimo y puede ayudar a determinar el perfil de los pacientes idóneos a recibir este tipo de intervención (AU)

Introduction. Invasive fungal disease (IFD) is an important cause of morbidity and mortality in haematological patients. Antifungal prophylaxis (AFP) is indicated for a number of clinical scenarios in this group of patients. The aim of this study was to reach a consensus on IFD prophylaxis in haematological patients in order to optimize their management. Methods. A committee of experts in haematology and infectious diseases compiled a survey of 79 items with controversial aspects about antifungal prophylaxis in haematological patients. The survey was evaluated in two rounds by a panel of experts following a modified Delphi methodology. Results. Forty-four experts in haematology and infectious diseases answered the survey. After two evaluation rounds, consensus was reached in 67 of the 79 items (84.8%), specifically 48 items were consensually agreed on (60.7%) and 19 were disagreed on (24.0%). Consensus was reached on prophylaxis candidates profiles and questions related to indications, mechanisms of action, spectrum of activity, toxicity and interactions of antifungal were elucidated. The usefulness of micafungin in IFD prophylaxis was particularly analysed. The consensus reached was that micafungin is an antifungal to be considered in this context as its safety profile and lower interaction potential may be advantageous. Conclusions. A broad consensus was found in the management of IFD prophylaxis in the haematological patient. This consensus provides practical indications about its optimal management and can help determine the profile of patients eligible for this type of intervention (AU)

Consenso sobre la vacunación anti-neumocócica en el adulto por riesgo de edad y patología de base. Actualización 2017 / Consensus document on pneumococcal vaccination in adults at risk by age and underlying clinical conditions. 2017 Update

La enfermedad neumocócica invasiva (ENI) y la neumonía neumocócica (NN) suponen un grave problema de salud entre los adultos de mayor edad y aquellos con determinadas condiciones y patologías de base, entre los que destacan los inmunodeprimidos y algunos inmunocompetentes, que les hacen más susceptibles a la infección y favorecen cuadros de mayor gravedad y peor evolución. Entre las estrategias para prevenir la ENI y la NN se encuentra la vacunación, aunque las coberturas vacunales son más bajas de lo deseable. Actualmente, existen 2 vacunas disponibles para el adulto. La vacuna polisacárida (VNP23), que se emplea en mayores de 2 años de edad desde hace décadas, es la que mayor número de serotipos (23) incluye, pero no genera memoria inmunitaria, los niveles de anticuerpos disminuyen con el tiempo, provoca un fenómeno de tolerancia inmunitaria y no actúa sobre la colonización nasofaríngea. La vacuna conjugada (VNC13) puede emplearse a cualquier edad de la vida a partir de las 6 semanas de vida y genera una respuesta inmunitaria más potente que la VNP23 frente a la mayoría de los 13 serotipos en ella incluidos. En el año 2013 las 16 Sociedades Científicas más directamente relacionadas con los grupos de riesgo para padecer ENI publicamos un documento de Consenso con una serie de recomendaciones basadas en las evidencias científicas respecto a la vacunación antineumocócica en el adulto con condiciones especiales y patología de base. Se estableció un compromiso de discusión y actualización ante la aparición de nuevas evidencias. Fruto de este trabajo de revisión, presentamos una actualización del anterior documento junto a otras nuevas Sociedades Científicas donde destaca la recomendación por edad (AU)

Invasive pneumococcal disease (IPD) and pneumococcal pneumonia (PP) represent an important health problem among aging adults and those with certain underlying pathologies and some diseases, especially immunosuppressed and some immunocompetent subjects, who are more susceptible to infections and present greater severity and worse evolution. Among the strategies to prevent IPD and PP, vaccination has its place, although vaccination coverage in this group is lower than desirable. Nowadays, there are 2 vaccines available for adults. Polysacharide vaccine (PPV23), used in patients aged 2 and older since decades ago, includes a greater number of serotypes (23), but it does not generate immune memory, antibody levels decrease with time, causes an immune tolerance phenomenon, and have no effect on nasopharyngeal colonization. PCV13 can be used from children 6 weeks of age to elderly and generates an immune response more powerful than PPV23 against most of the 13 serotypes included in it. In the year 2013 the 16 most directly related to groups of risk of presenting IPD publised a series of vaccine recommendations based on scientific evidence regarding antipneumococcal vaccination in adults with underlying pathologies and special conditions. A commitment was made about updating it if new scientific evidence became available. We present an exhaustive revised document focusing mainly in recommendation by age in which some more Scientific Societies have been involved (AU)

Consenso sobre la vacunación anti-neumocócica en el adulto con patología de base / No disponible

La enfermedad neumocócica invasiva (ENI) supone un grave problema de salud entre los adultos con determinadas condiciones y patologías de base, entre los que destacan los inmunodeprimidos y algunos inmunocompetentes, que les hacen más susceptibles a la infección y favorecen cuadros de mayor gravedad y peor evolución. Entre las estrategias para prevenir la ENI se encuentra la vacunación, aunque las coberturas vacunales en este grupo son más bajas de lo deseable. Actualmente, existen 2 vacunas disponibles para el adulto. La vacuna polisacárida (VNP23), que se emplea en mayores de 2 años de edad desde hace décadas, es la que mayor número de serotipos (23) incluye, pero no genera memoria inmunitaria, los niveles de anticuerpos disminuyen con el tiempo, provoca un fenómeno de tolerancia inmunitaria y no actúa sobre la colonización nasofaríngea. La vacuna conjugada (VNC13) puede emplearse desde lactantes hasta la edad adulta (la indicación en mayores de 18 años ha recibido la aprobación de la Agencia Europea del Medicamento en julio de 2013) y genera una respuesta inmunitaria más potente que la VNP23 frente a la mayoría de los 13 serotipos en ella incluidos. Las 16 Sociedades Científicas más directamente relacionadas con los grupos de riesgo para padecer ENI han trabajado en la discusión y elaboración de una serie de recomendaciones vacunales basadas en las evidencias científicas respecto a la vacunación anti-neumocócica en el adulto con condiciones y patología de base que se detallan en este documento. Se trata de un documento “vivo” que seguirá actualizándose ante nuevas evidencias científicas disponibles (AU)

Response to rituximab-based therapy and risk factor analysis in Epstein Barr Virus-related lymphoproliferative disorder after hematopoietic stem cell transplant in children and adults: a study from the Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation.

BACKGROUND: The objective of this analysis was to investigate prognostic factors that influence the outcome of Epstein-Barr virus (EBV)-related posttransplant lymphoproliferative disorder (PTLD) after a rituximab-based treatment in the allogeneic hematopoietic stem cell transplant (HSCT) setting. METHODS: A total of 4466 allogeneic HSCTs performed between 1999 and 2011 in 19 European Group for Blood and Marrow Transplantation centers were retrospectively analyzed for PTLD, either biopsy-proven or probable disease. RESULTS: One hundred forty-four cases of PTLD were identified, indicating an overall EBV-related PTLD frequency of 3.22%, ranging from 1.16% for matched-family donor, 2.86% for mismatched family donor, 3.97% in matched unrelated donors, and 11.24% in mismatched unrelated donor recipients. In total, 69.4% patients survived PTLD. Multivariable analysis showed that a poor response of PTLD to rituximab was associated with an age ≥30 years, involvement of extralymphoid tissue, acute GVHD, and a lack of reduction of immunosuppression upon PTLD diagnosis. In the prognostic model, the PTLD mortality increased with the increasing number of factors: 0-1, 2, or 3 factors being associated with mortality of 7%, 37%, and 72%, respectively (P < .0001). Immunosuppression tapering was associated with a lower PTLD mortality (16% vs 39%), and a decrease of EBV DNAemia in peripheral blood during therapy was predictive of better survival. CONCLUSIONS: More than two-thirds of patients with EBV-related PTLD survived after rituximab-based treatment. Reduction of immunosuppression was associated with improved outcome, whereas older age, extranodal disease, and acute graft-vs-host disease predicted poor outcome.

Infección pulmonar recurrente por Aspergillus fumigatus con resistencia a múltiples triazoles en un paciente español con leucemia mieloide crónica / Breakthrough pulmonary Aspergillus fumigatus infection with multiple triazole resistance in a Spanish patient with chronic myeloid leukemia

Antecedentes. Un paciente sometido a un trasplante alogénico de progenitores hematopoyéticos se presentó con aspergilosis pulmonar crónica, asociada a enfermedad pulmonar injerto contra huésped, y fue tratado durante un período prolongado con diversos antimicóticos administrados como profilaxis, tratamiento de combinación y tratamiento de mantenimiento. El paciente experimentó una aspergilosis pulmonar invasiva recurrente debida a Aspergillus fumigatus tras el tratamiento antimicótico prolongado. Material y métodos. Se analizarán diversos aislamientos. Los primeros aislamientos eran sensibles in vitro a todos los azoles. No obstante, tras tratamiento prolongado con itraconazol y voriconazol, a partir de líquido de lavado broncopulmonar (LBA) cuando el paciente experimentó una infección invasiva, se cultivó un aislamiento de A. fumigatus resistente a múltiples azólicos y se observaron lesiones cavitarias. Resultados. El análisis de los mecanismos de resistencia que actuaron en la última cepa nos condujo a publicar un artículo sobre el primer aislamiento en España de una cepa de A. fumigatus resistente a un azol que albergaba la mutación L98H en combinación con una alteración de repeticiones en tándem (RT) en el gen CYP51A (TR-L98H). El tratamiento prolongado con un azol puede aumentar la selección de cepas con una disminución de la sensibilidad a estos fármacos. Sin embargo, en este caso, puesto que los aislamientos eran genéticamente diferentes, se sugirió que la resistencia no estuvo inducida durante el tratamiento prolongado con azólicos sino que el paciente adquirió este aislamiento resistente del entorno y fue seleccionado por el tratamiento. Conclusiones. Los hallazgos del presente estudio sugieren que en todos los tratamientos crónicos con antimicóticos, en particular con azólicos, puede ser necesaria la obtención de muestras repetidas, al igual que la realización de exámenes a intervalos regulares de la sensibilidad de las cepas aisladas, ya que pueden seleccionarse aislamientos resistentes(AU)

Background. An allogeneic hematopoietic cell transplantation (allo-HCT) patient presented with chronic pulmonary aspergillosis associated to pulmonary graft versus host disease (GVHD) and was treated for a long time with several antifungal agents that were administered as prophylaxis, combination therapies, and maintenance treatment. The patient suffered from a breakthrough invasive pulmonary aspergillosis due to Aspergillus fumigatus after long-term antifungal therapy. Material and methods. Several isolates were analyzed. First isolates were susceptible in vitro to all azole agents. However, after prolonged treatment with itraconazole and voriconazole a multiple azole resistant A. fumigatus isolate was cultured from bronchoalveolar lavage (BAL) when the patient was suffering from an invasive infection, and cavitary lesions were observed. Results. Analysis of the resistant mechanisms operating in the last strain led us to report the first isolation in Spain of an azole resistant A. fumigatus strain harboring the L98H mutation in combination with the tandem repeat (TR) alteration in CYP51A gene (TR-L98H). Long-term azole therapy may increase the risk of resistance selecting strains exhibiting reduced susceptibility to these compounds. However, since the isolates were genetically different the suggestion that could be made is that the resistance was not induced during the prolonged azole therapy but the patient might simply have acquired this resistant isolate from the environment, selected by the therapy. Conclusions. These findings suggest that in all long-term treatments with antifungal agents, especially with azoles, repeated sampling and regular susceptibility testing of strains isolated is necessary as resistant isolates could be selected(AU)

Recomendaciones sobre el tratamiento de la enfermedad fúngica invasiva por Aspergillus spp. y otros hongos filamentosos de la Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica (SEIMC). Actualización 2011 (AU) / Guidelines for the Treatment of Invasive Fungal Disease by Aspergillus spp. and Other Fungi Issued by the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC). 2011 Update

El presente trabajo actualiza las recomendaciones para el tratamiento de la aspergilosis invasiva y las infecciones producidas por otros hongos filamentosos, elaboradas por el Grupo de Estudio de Micología Médica (GEMICOMED), incluido dentro de la Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica (SEIMC). Se analiza el tratamiento de estas infecciones en cuatro grupos de patologías médicas: oncohematología, trasplante de órgano sólido, paciente crítico ingresado en cuidados intensivos y pediatría. Se realiza una revisión exhaustiva de las novedades terapéuticas y de los niveles de evidencia. Estas guías han sido elaboradas, siguiendo las normativas de la SEIMC, por un grupo de trabajo formado por especialistas en enfermedades infecciosas, microbiología clínica, medicina intensiva, pediatría y oncohematología. Se proporciona también unas recomendaciones para la prevención de estas infecciones (AU)

The guidelines on the treatment of invasive fungal disease by Aspergillus spp. and other fungi issuedby the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) are presented. These recommendations are focused on four clinical categories: oncology-haematology patients, solid organtransplant recipients, patients admitted to intensive care units, and children. An extensive review ismade of therapeutical advances and scientific evidence in these settings. These guidelines have been prepared according the SEIMC consensus rules by a working group composed of specialists in infectious diseases, clinical microbiology, critical care medicine, paediatrics and oncology-haematology. Specific recommendations on the prevention of fungal infections in these patients are included (AU)

Update on fungemia in oncology and hematology

El trabajo que se presenta es una revisión de la bibliografía reciente más relevante del último año publicadaen relación con la funginemia en pacientes oncohematológicos. Un grupo multidisciplinar compuesto pordiferentes especialistas españoles con interés en este campo revisan los artículos más novedosos. Los trabajospertenecen a áreas de epidemiología, factores de riesgo, patogénesis, diagnóstico, evolución, prevencióny tratamiento. Se analizan diferentes aspectos, incluyendo estrategias del manejo de la fiebre en el pacienteneutropénico. La identificación precoz de factores de riesgo de infección fúngica, así como de los factoresde riesgo de infección por cepas resistentes a fluconazol es objetivo de especial interés (AU)

The present article is an update of the literature on fungemia in onco-hematologic patients. Amultidisciplinary group of Spanish physicians with an interest in this field selected the most importantpapers published lately. Papers from the fields of epidemiology, risk factors, pathogenesis, diagnosis,outcome, prevention and treatment are discussed. Important aspects of these studies include theassessment of different strategies in the management of fever in neutropenic patients. Moreover, earlyidentification of patients at risk of fungal infections, as well as identification of patients at risk forfluconazole-resistant strains are topics of increasing interest (AU)

Immune response to the 23-valent polysaccharide pneumococcal vaccine after the 7-valent conjugate vaccine in allogeneic stem cell transplant recipients: results from the EBMT IDWP01 trial.

The current recommendations for active immunization after stem cell transplant (SCT) include 3 doses of 7-valent pneumococcal conjugate vaccine (PCV7) from 3 months after transplant, followed by a 23-valent polysaccharide pneumococcal vaccine (PPV23). However, until now, the immune response to PPV23 after PCV7 has not been assessed after SCT. In the EBMT IDWP01 trial, 101 patients received 1 dose of PPV23 at 12 or 18 months, both after 3 doses of PCV7. The efficacy of PPV23 was assessed 1 month later and at 24 months after transplant by the pneumococcal serotype 1 and 5 antibody levels. Serotype 1 and 5 are not included in PCV7. Although the geometric mean concentrations were significantly higher 1 month after PPV23, for both antigens, the response rates (> or =0.15 microg/mL), in the range of 68-94%, were not different between groups independent of the assessment date. One PPV23 dose after 3 PCV7 doses, already known to increase the response to PCV7, also extends the serotype coverage given 12 or 18 months after transplant.

Profilaxis antifúngica en pacientes oncohematológicos: revisión de la bibliografía médica y recomendaciones / Antifungal prophylaxis in oncohematologic patients: Literature review and recommendations

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Meropenem: experiencia clínica en el paciente neutropénico / No disponible

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Tratamiento de las infecciones fúngicas en pacientes con neoplasias hematológicas / Treatment of fungal infections in patients with hematologic neoplasia

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Actualización de las infecciones pulmonares en los pacientes con procesos hematológicos malignos y en los receptores de células madre hematopoyéticas / Update on pulmonary infections in patients with hematologic malignancies and hematopoietic stem cell recipients

The present article is an update of the literature onpulmonary infections in patients with hematologicmalignancies and in hematopoietic stem cell recipients.A multidisciplinary group of Spanish physicians with aninterest in these infections selected the most importantpapers produced in the field during 2005 and 2006. Oneof the members of the group discussed the contentof each of the selected papers, with a critical review byother members of the panel.After a review of the state of the art, papers from the fieldsof viral and fungal infections were discussed by the group(AU)

El presente artículo es una actualización de la literaturasobre infecciones pulmonares en los pacientes conprocesos hematológicos malignos y en los receptores decélulas madre hematopoyéticas.Un grupo multidisciplinario de médicos españoles coninterés en estas infecciones seleccionó los trabajos másimportantes publicados sobre el tema durante 2005 y 2006.Un miembro del grupo discutió el contenido de cadaartículo seleccionado, y otros componentes del panelefectuaron una revisión crítica del trabajo.Después de una revisión del estado del arte, el grupodiscutió los artículos sobre las infecciones víricasy micóticas(AU)