Single-point and kinetics of peripheral residual disease by mass spectrometry to predict outcome in patients with high risk smoldering multiple myeloma included in the GEM-CESAR trial.

The value of quantitative immunoprecipitation mass spectrometry (QIP-MS) to identify the M-protein is being investigated in patients with monoclonal gammopathies but no data are yet available in high-risk smoldering myeloma (HRsMM). We have therefore investigated QIP-MS to monitor peripheral residual disease (PRD) in 62 HRsMM patients enrolled in the GEM-CESAR trial. After 24 cycles of maintenance, detecting the M-protein by MS or clonal plasma cells by NGF identified cases with a significantly shorter median PFS (mPFS; MS: not reached vs 1,4 years, p=0.001; NGF: not reached vs 2 years, p=0.0002) but reaching CR+sCR did not discriminate patients with different outcome. With NGF as a reference, the combined results of NGF and MS showed a high negative predictive value (NPV) of MS: 81% overall and 73% at treatment completion. When sequential results were considered, sustained negativity by MS or NGF was associated with a very favorable outcome with a mPFS not yet reached vs 1.66 years and 2.18 years in cases never attaining PRD or minimal residual disease (MRD) negativity, respectively. We can thus conclude that 1) the standard response categories of the IMWG do not seem to be useful for treatment monitoring in HRsMM patients, 2) MS could be used as a non-invasive, clinical valuable tool with the capacity of guiding timely bone marrow evaluations (based on its high NPV with NGF as a reference) and 3) similarly to NGF, sequential results of MS are able identify a subgroup of HRsMM patients with long-term disease control. This study was registered at www.clinicaltrials.gov (ClinicalTrials.gov identifier: NCT02415413).

Comparative Review of the Current and Future Strategies to Evaluate Bone Marrow Infiltration at Diffuse Large B-Cell Lymphoma Diagnosis.

Diffuse large B-cell lymphoma (DLBCL) requires a complete staging at diagnosis that may have prognostic and therapeutic implications. The role of bone marrow (BM) biopsy (BMB) is controversial in the era of nuclear imaging techniques. We performed a comparative review of 25 studies focused on BM evaluation at DLBCL diagnosis, including at least two of the following techniques: BMB, flow cytometry, and positron emission tomography (PET-FDG). The report about BM involvement (BMi), diagnostic accuracy, and prognostic significance was collected and compared among techniques. A concordance analysis between BMB, FCM, and PET was also performed, and we deeply evaluated the implications of the different types of BMi: concordant by LBCL or discordant by low-grade B-cell lymphoma for both BMB and FCM, and focal or diffuse uptake pattern for PET. As a main conclusion, BMB, FCM, and PET are complementary tools that provide different and clinically relevant information in the assessment of BMi in newly diagnosed DLBCL.

A Phase I/IIa Prospective, Randomized, Open-Label Study on the Safety and Efficacy of Nebulized Liposomal Amphotericin for Invasive Pulmonary Aspergillosis.

Although nebulized liposomal amphotericin B (NLAB) is being used in invasive pulmonary aspergillosis (IPA) prophylaxis, no clinical trial has shown its efficacy as a therapeutic strategy. NAIFI is the inaugural randomized, controlled clinical trial designed to examine the safety and effectiveness of NLAB (dosage: 25 mg in 6 mL, three times per week for 6 weeks) against a placebo, in the auxiliary treatment of IPA. Throughout the three-year clinical trial, thirteen patients (six NLAB, seven placebo) were included, with 61% being onco-hematological with less than 100 neutrophils/µL. There were no significant differences noted in their pre- and post-nebulization results of forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and oxygen saturation between the groups. Neither bronchospasm nor serum amphotericin B levels were reported in any patients given NLAB. 18F-Fluorodeoxyglucose positron emission tomography (FDG-PET-TC) was carried out at the baseline and after 6 weeks. A notable decrease in median SUV (standardized uptake value) was observed in NLAB patients after 6 weeks (-3.6 vs. -0.95, p: 0.039, one tail). Furthermore, a reduction in serum substance galactomannan and beta-D-Glucan was identified within NLAB recipients. NLAB is well tolerated and safe for patients with IPA. Encouraging indirect efficacy data have been derived from image monitoring or biomarkers. However, further studies involving more patients are necessary.

Real-World Experience with Isavuconazole in Allogeneic Stem Cell Transplantation in Spain.

Invasive fungal infections (IFI) pose a significant complication after hematopoietic stem cell transplantation (HSCT). Isavuconazole (ISV) is a new generation azole with a favourable adverse effect and interaction profile approved for the treatment of invasive aspergillosis and mucormycosis. We analyzed the indications, effectiveness, adverse event profile and drug interaction management of ISV in the real-world setting in adults who received allogeneic-HSCT (allo-HSCT) within the Spanish Group of HSCT and Cell Therapy (GETH-TC). We conducted a multicenter retrospective study of all consecutive adult allo-HSCT recipients (≥18 years) who received ISV either for IFI treatment or prophylaxis, from December 2017 to August 2021, in 20 centers within the Spanish Group of Hematopoietic Stem Cell Transplantation and Cell Therapy (GETH-TC). A total of 166 adult allografted patients who received ISV from 2017 to 2021 were included. Median age was 48 years with 43% females. In 81 (49%) patients, ISV was used for treatment of IFI, and in 85 (51%) for prophylaxis. Median duration of ISV administration for IFI treatment was 57 days (range 31-126) and 86 days (range 33-196) for prophylaxis. Most frequent indication for treatment was invasive aspergillosis (78%), followed by mucormycosis (6%). Therapeutic success (45%) was the most frequent reason for ISV withdrawal. In the prophylaxis group, the resolution of IFI risk factors was the most frequent reason for withdrawal (62%). Six (7%) breakthrough IFI were reported. The majority of patients (80%) presented pharmacologic interactions. Twenty-one patients (13%) reported adverse events related to ISV, mainly liver biochemistry abnormalities, which led to ISV withdrawal in 7 patients (4%). ISV was effective and well tolerated for IFI treatment and prophylaxis, with a manageable interaction profile.

Omicron SARS-CoV-2 infection management and outcomes in patients with hematologic disease and recipients of cell therapy.

Introduction: Scarce real-life data exists for COVID-19 management in hematologic disease (HD) patients in the Omicron era. Purpose: To assess the current clinical management and outcome of SARS-CoV-2 infection diagnosed, identify the risk factors for severe outcomes according to the HD characteristics and cell therapy procedures in a real-world setting. Methods: A retrospective observational registry led by the Spanish Transplant Group (GETH-TC) with 692 consecutive patients with HD from December 2021 to May 2023 was analyzed. Results: Nearly one-third of patients (31%) remained untreated and presented low COVID-19-related mortality (0.9%). Nirmatrelvir/ritonavir was used mainly in mild COVID-19 cases in the outpatient setting (32%) with a low mortality (1%), while treatment with remdesivir was preferentially administered in moderate-to-severe SARS-CoV-2 infection cases during hospitalization (35%) with a mortality rate of 8.6%. The hospital admission rate was 23%, while 18% developed pneumonia. COVID-19-related mortality in admitted patients was 14%. Older age, autologous hematopoietic stem cell transplantation (SCT), chimeric antigen receptor T-cell therapy, corticosteroids and incomplete vaccination were factors independently associated with COVID-19 severity and significantly related with higher rates of hospital admission and pneumonia. Incomplete vaccination status, treatment with prior anti-CD20 monoclonal antibodies, and comorbid cardiomyopathy were identified as independent risk factors for COVID-19 mortality. Conclusions: The results support that, albeit to a lower extent, COVID-19 in the Omicron era remains a significant problem in HD patients. Complete vaccination (3 doses) should be prioritized in these immunocompromised patients. The identified risk factors may help to improve COVID-19 management to decrease the rate of severe disease, ICU admissions and mortality.

COVID-19 Outcomes in Patients with Hematologic Malignancies in the Era of COVID-19 Vaccination and the Omicron Variant.

A greater understanding of clinical trends in COVID-19 outcomes among patients with hematologic malignancies (HM) over the course of the pandemic, particularly the Omicron era, is needed. This ongoing, observational, and registry-based study with prospective data collection evaluated COVID-19 clinical severity and mortality in 1818 adult HM patients diagnosed with COVID-19 between 27 February 2020 and 1 October 2022, at 31 centers in the Madrid region of Spain. Of these, 1281 (70.5%) and 537 (29.5%) were reported in the pre-Omicron and Omicron periods, respectively. Overall, patients aged ≥70 years (odds ratio 2.16, 95% CI 1.64-2.87), with >1 comorbidity (2.44, 1.85-3.21), or with an underlying HM of chronic lymphocytic leukemia (1.64, 1.19-2.27), had greater odds of severe/critical COVID-19; odds were lower during the Omicron BA.1/BA.2 (0.28, 0.2-0.37) or BA.4/BA.5 (0.13, 0.08-0.19) periods and among patients vaccinated with one or two (0.51, 0.34-0.75) or three or four (0.22, 0.16-0.29) doses. The hospitalization rate (75.3% [963/1279], 35.7% [191/535]), rate of intensive care admission (30.0% [289/963], 14.7% [28/191]), and mortality rate overall (31.9% [409/1281], 9.9% [53/536]) and in hospitalized patients (41.3% [398/963], 22.0% [42/191]) decreased from the pre-Omicron to Omicron period. Age ≥70 years was the only factor associated with higher mortality risk in both the pre-Omicron (hazard ratio 2.57, 95% CI 2.03-3.25) and Omicron (3.19, 95% CI 1.59-6.42) periods. Receipt of prior stem cell transplantation, COVID-19 vaccination(s), and treatment with nirmatrelvir/ritonavir or remdesivir were associated with greater survival rates. In conclusion, COVID-19 mortality in HM patients has decreased considerably in the Omicron period; however, mortality in hospitalized HM patients remains high. Specific studies should be undertaken to test new treatments and preventive interventions in HM patients.

Survival after allogeneic transplantation according to pretransplant minimal residual disease and conditioning intensity in patients with acute myeloid leukemia.

Background: The measurement of minimal residual disease (MRD) by multiparametric flow cytometry (MFC) before hematopoietic stem cell transplantation (HSCT) in patients with acute myeloid leukemia (AML) is a powerful prognostic factor. The interaction of pretransplant MRD and the conditioning intensity has not yet been clarified. Objective: The aim of this study is to analyze the transplant outcomes of patients with AML who underwent HSCT in complete remission (CR), comparing patients with positive MRD (MRD+) and negative MRD (MRD-) before HSCT, and the interaction between conditioning intensity and pre-HSCT MRD. Study design: We retrospectively analyzed the transplant outcomes of 118 patients with AML who underwent HSCT in CR in a single institution, comparing patients with MRD+ and MRD- before HSCT using a cutoff of 0.1% on MFC, and the interaction between conditioning intensity and pre-HSCT MRD. Results: Patients with MRD+ before HSCT had a significantly worse 2-year (2y) event-free survival (EFS) (56.5% vs. 32.0%, p = 0.018) than MRD- patients, due to a higher cumulative incidence of relapse (CIR) at 2 years (49.0% vs. 18.0%, p = 0.002), with no differences in transplant-related mortality (TRM) (2y-TRM, 19.0% and 25.0%, respectively, p = 0.588). In the analysis stratified by conditioning intensity, in patients who received MAC, those with MRD- before HSCT had better EFS (p = 0.009) and overall survival (OS) (p = 0.070) due to lower CIR (p = 0.004) than MRD+ patients. On the other hand, the survival was similar in reduced intensity conditioning (RIC) patients regardless of the MRD status. Conclusions: Patients with MRD+ before HSCT have worse outcomes than MRD- patients. In patients who received MAC, MRD- patients have better EFS and OS due to lower CIR than MRD+ patients, probably because they represent a more chemo-sensitive group. However, among RIC patients, results were similar regardless of the MRD status.

18F-FDG-PET/CT response after first-line treatment as a prognostic factor for survival in peripheral T-cell lymphoma: a Spanish retrospective study.

BACKGROUND: An accurate assessment of tumor viability after first-line treatment is critical for predicting treatment failure in peripheral T-cell lymphomas (PTCLs). 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) has been adopted as the preferred assessment method in clinical trials, but its impact in clinical practice should be examined. This study aims to determine the prognostic significance of18F-FDG-PET/CT for survival following first-line treatment in PTCL patients. RESEARCH DESIGN AND METHODS: Retrospective observational study including 175 patients diagnosed with PTCL between 2008 and 2013 in 13 Spanish sites. RESULTS: Fifty patients were evaluated with18F-FDG-PET/CT following first-line therapy: 58% were18F-FDG-PET/CT-negative and 42% were18F-FDG-PET/CT-positive. Disease progression occurred in 37.9% of18F-FDG-PET/CT-negative patients and in 80.9% of18F-FDG-PET/CT-positive patients (p = 0.0037). Median progression-free survival and overall survival were 67 and 74 months for18F-FDG-PET/CT-negative patients, and 5 (p < 0.0001) and 10 months (p < 0.0001), respectively, in18F-FDG-PET/CT-positive patients. After multivariate analysis, only B symptoms emerged as a negative predictive factor of complete response (RR 7.08; 95% CI 1.60-31.31; p = 0.001). CONCLUSIONS: 18F-FDG-PET/CT identifies high-risk PTCL patients who will have poor prognosis and survival following first-line treatment. However, more research is needed to confirm the best treatment options for PTCL patients.

Curative Strategy for High-Risk Smoldering Myeloma: Carfilzomib, Lenalidomide, and Dexamethasone (KRd) Followed by Transplant, KRd Consolidation, and Rd Maintenance.

PURPOSE: Early treatment of high-risk smoldering myeloma has been shown to delay progression to multiple myeloma (MM). We conducted this trial with curative intention using a treatment approach employed for newly diagnosed patients with MM. METHODS: Patients with high-risk smoldering myeloma (>50% progression risk at 2 years) and transplant candidates were included and received induction therapy with carfilzomib, lenalidomide, and dexamethasone (KRd), six cycles, followed by high-dose melphalan (200 mg/m2) autologous stem-cell transplantation (HDM-ASCT), two KRd consolidation cycles, and Rd maintenance for 2 years. The primary end point was undetectable measurable residual disease (uMRD) rate by next-generation flow after ASCT. Sustained uMRD 4 years after ASCT was the secondary end point. RESULTS: Between June 2015 and June 2017, 90 patients were included, and 31% met at least one SixtyLightchain MRI (SLiM)-hypercalcemia, renal impairment, anemia, bone disease (CRAB) criterion. After a median follow-up of 70.1 months, 3 months after ASCT, in the intention-to-treat population, 56 (62%) of 90 patients had uMRD, and 4 years later, it was sustained in 29 patients (31%). Five patients progressed to MM, and the 70-month progression rate was 94% (95% CI, 84 to 89). The presence of any SLiM CRAB criteria predicted progression to MM (four of the five patients; hazard ratio, 0.12; 95% CI, 0.14 to 1.13; P = .03). Thirty-six patients showed biochemical progression, and failure to achieve uMRD at the end of treatment predicted it. The 70-month overall survival was 92% (95% CI, 82 to 89). Neutropenia and infections were the most frequent adverse events during treatment, resulting in one treatment-related death. Three second primary malignancies have been reported. CONCLUSION: Although a longer follow-up is needed, this curative approach is encouraging and more effective than active MM, with 31% of the patients maintaining the uMRD 4 years after HDM-ASCT.

Use of micafungin as antifungal prophylaxis in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) in Spain (GETH-MIC) / Profilaxis antifúngica con micafungina en pacientes que reciben un trasplante alogénico de progenitores hematopoyéticos (alo-TPH) en España (GETH-MIC)

INTRODUCTION: The fungal infections remain an important problem in the allogeneic stem cell trasnsplantation (allo-SCT) setting and thus, anti-fungal prophylaxis is commonly used. The antifungal drug should offer activity, at least against Candida and Aspergillus spp., a good safety profile and low probability interactions. Micafungin could theoretically fulfill these requisites. The aim of the study was to describe the experience with micafungin as primary prophylaxis in patients undergoing allo-SCT in a cohort of Spanish centres, and to evaluate its efficacy and tolerability in this population. MATERIAL AND METHODS: Retrospective multicentre observational study including all consecutive adult patients admitted for allo-SCT in participating centres of the Grupo Español de Trasplante Hematopoyético (GETH), from January 2010 to December 2013, who received micafungin as primary prophylaxis during the neutropenic period. RESULTS: A total of 240 patients from 13 centres were identified and 159 patients were included for the analysis. Most patients (95.6%) received 50 mg/day of micafungin. During the follow-up, 7 (4.4%) patients developed breakthrough invasive fungal disease, 1 proven and 6 probable; one patient discontinued the drug because of serious drug interactions. Prophylaxis with micafungin was considered effective in 151 (94.9%) patiens. CONCLUSIONS: According to our experience, micafungin is an appropriate alternative for antifungal prophylaxis in patients undergoing an allo-HSCT, because its efficacy, its low profile of drug interactions and side-effects

INTRODUCCIÓN: Las infecciones fúngicas siguen representando un problema en el trasplante alogénico de progenitores hematopoyéticos (alo-TPH) por lo que es habitual el uso de profilaxis antifúngica en estos PACIENTES: El tratamiento antifúngico debe presentar al menos actividad frente a Candida y Aspergillus spp, un buen perfil de seguridad y baja probabilidad de infecciones, siendo micafungina una de las opciones que podría cumplir todos estos requisitos. El objetivo del estudio fue describir la experiencia con micafungina como profilaxis primaria en pacientes sometidos a alo-TPH en una cohorte de hospitales españoles, y evaluar su eficacia y seguridad en esta población. MATERIAL Y MÉTODOS: Estudio retrospectivo multicéntrico observacional consecutivo de todos los pacientes adultos ingresados para alo-TPH en los centros del Grupo Español de Trasplante Hematopoyético (GETH) desde enero de 2010 a diciembre de 2013 y que recibieron micafungina como profilaxis primaria durante el periodo de neutropenia. RESULTADOS: Se identificaron 240 pacientes de 13 hospitales y 159 fueron incluidos para el análisis. La mayoría (95.6%) de ellos recibieron dosis de 50mg/día de micafungina. Durante el seguimiento, 7 (4.4%) pacientes desarrollaron infecciones de brecha, 1 probada y 6 probables; en un paciente se suspendió el tratamiento por interacciones medicamentosas graves. La profilaxis con micafungina se consideró efectiva en el 94,9% de los pacientes (151 de 159). CONCLUSIONES: En base a nuestros resultados, consideramos que micafungina es una buena alternativa como profilaxis antifúngica en pacientes sometidos a alo-TPH, por su eficacia, el bajo riesgo de interacciones y de efectos adversos

Nocardiosis sistémica en pacientes con aplasia medular adquirida: descripción de 2 casos / Systemic nocardiosis in acquired aplastic anaemia: Report of 2 cases

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Bacteriemia e infección del catéter vascular en el ámbito hematológico: posicionamiento y actitudes de manejo basados en el método Delphi / Bacteraemia and infection of the vascular catheter in the haematology patient: positioning and management based on the Delphi method

Introducción. Las complicaciones infecciosas son una causa importante de morbi-mortalidad en los pacientes hematológicos con neutropenia febril. El objetivo del presente trabajo fue desarrollar un documento de recomendaciones consensuado para optimizar el manejo del paciente hematológico con neutropenia febril o infecciones por catéteres vasculares en áreas en las que no se dispone de una sólida evidencia científica. Material y métodos. Tras la revisión de las evidencias científico-médicas, un comité científico formado por especialistas expertos en hematología y enfermedades infecciosas elaboró una encuesta con 55 aseveraciones. Para el consenso se utilizó un método Delphi modificado con dos rondas de evaluación. Resultados. La encuesta fue respondida online por 52 especialistas en hematología y en enfermedades infecciosas. Tras las dos rondas de evaluación fue posible el consenso en 43 de los 55 ítems planteados (un 78,2%): 40 en el acuerdo y 3 en el desacuerdo. Con ello, se proporcionan una serie de recomendaciones relativas al tratamiento antibiótico empírico del paciente con neutropenia febril, a cuestiones relacionadas con mecanismos de acción, toxicidad y sinergia de los antibióticos en este contexto, a las modificaciones del tratamiento antibiótico en el curso de la neutropenia febril y al manejo de las infecciones de catéter vascular central en el ámbito hematológico. Conclusiones. Existe un alto grado de acuerdo entre los expertos consultados sobre algunos aspectos controvertidos relativos al manejo de la neutropenia febril y la infección por catéter en pacientes hematológicos. Este acuerdo se ha traducido en unas recomendaciones que pueden ser de utilidad en la práctica clínica (AU)

Introduction. Infectious complications are an important cause of morbidity and mortality in haematological patients with febrile neutropenia. The aim of this study was to develop a consensus document of recommendations to optimize the management of febrile neutropenic patients with haematological or vascular catheter infections in areas where there is no solid scientific evidence. Materials and Methods. After reviewing the scientific evidence, a scientific committee composed of experts in haematology and infectious diseases developed a survey with 55 statements. A two- round modified Delphi method was used to achieve consensus. Results. The online survey was answered by 52 experts in the field of haematology and infectious diseases. After two rounds of evaluation, a consensus was possible in 43 of the 55 statements (78.2%): 40 in agreement and 3 in disagreement. Recommendations are given related to empirical antibiotic treatment of patients with febrile neutropenia, mechanisms of action, toxicity and synergism of antibiotics in this context, modifications of antibiotic treatment in the course of febrile neutropenia, and the management of central vascular catheter infections in the haematological setting. Conclusions. There is a high degree of agreement among experts on some controversial issues concerning the management of febrile neutropenia and catheter infection in hematologic patients. This agreement has resulted in recommendations that may be useful in clinical practice (AU)

Treatment of invasive fungal infections in high risk hematological patients. The outcome with liposomal amphotericin B is not negatively affected by prior administration of mold-active azoles

Existe cierta inquietud sobre una reducción del efecto de la anfotericina B liposomal (L-AmB) administrada secuencialmente después de la administración de azoles activos frente a mohos debido a un posible antagonismo en su mecanismo antifúngico. Para investigar este posible efecto en la práctica clínica, hemos estudiado retrospectivamente 182 pacientes hematológicos con infecciones fúngicas invasivas (IFI) de alto riesgo que fueron tratados con L- AmB. En total, 96 pacientes (52,7%) tenían IFI posible, 52 (28,6%) probable y 34 (18,7%) probada de acuerdo con la clasificación de la EORTC. La mayoría presentaban aspergilosis invasiva. Comparamos los pacientes con exposición previa a azoles activos frente a mohos (n=100) con aquellos no expuestos (n=82). El grupo con exposición previa a azoles activos frente a mohos incluía más pacientes con características de alto riesgo de IFI, como leucemia mieloide aguda (p<0,05) y neutropenia prolongada (p<0,05). Se alcanzó una respuesta favorable en la IFI, definida como una respuesta completa o parcial, en 75,0% y 74,4% de los pacientes de la cohorte completa y en 66,0% y 74,4% de los pacientes con IFI probable o probada en los dos grupos. Ninguna de estas diferencias fue significativa. El análisis multivariante mostró que la enfermedad basal y la disfunción renal eran factores adversos para la respuesta en la IFI (p<0,05). La supervivencia fue peor en los pacientes tratados con azoles de amplio espectro (p<0,05) y en aquellos en los que no se resolvió la neutropenia (p<0,05). En conclusión, la eficacia del tratamiento con LAmB de una infección fúngica de brecha probablemente no se vea afectada por la exposición previa a un tratamiento profiláctico con azoles activos frente a mohos, dependiendo la supervivencia más bien de los factores del huésped y de la enfermedad de base(AU)

There are concerns of a reduced effect of liposomal amphotericin B (L-AmB) given sequentially after mold-active azoles due to a possible antagonism in their antifungal mechanism. To investigate this possible effect in the clinic, we retrospectively studied 182 high risk hematologic patients with invasive fungal infections (IFI) who were treated with L-AmB. Overall, 96 patients (52.7%) had possible, 52 (28.6%) probable and 34 (18.7%) proven IFI according to EORTC classification. Most had suspected or proven invasive aspergillosis. We compared patients with prior exposure to mold-active azoles (n=100) to those having not (n=82). The group with prior mold-active azoles included more patients with poor risk features for IFI as acute myeloid leukemia (p<0.05) and prolonged neutropenia (p<0.05). A favorable response in the IFI, defined as a complete or partial response, was achieved in 75% and 74.4% of patients in the whole cohort, and in 66% and 74.4% of patients with probable or proven IFI in the two groups. None of these differences were significant. Multivariate analysis showed that refractory baseline disease and renal dysfunction were adverse factors for response in the IFI (p<0.05). Survival was poorer for patients with prior broad spectrum azoles (p<0.05), and for those who did not recover from neutropenia (p<0.05). In conclusion, the effectiveness of treatment of breakthrough fungal infection with L-AmB is not likely to be affected by prior exposure to mold-active azoles prophylaxis, but survival largely depends on host and disease factors(AU)

Guía de consenso nacionales para el estudio y tratamiento de los pacientes con leucemia linfocítica crónica / National guidelines for the management of patients with chronic lymphocytic leukemia

La leucemia linfocítica crónica es el síndrome linfoproliferativo crónico más frecuente en nuestro país, existiendo una amplia heterogeneidad en su abordaje clínico. En la actualidad, en España no se dispone de guías de consenso nacionales similares a las publicadas en otros países para su diagnóstico, clasificación pronóstica y tratamiento. El presente trabajo revisa la evidencia científica actual y aborda cuestiones relacionadas con el diagnóstico, el estudio de extensión, la presencia de comorbilidades y la clasificación de escalas pronósticas, los esquemas de tratamiento habituales estratificados por grupos de riesgo, el tratamiento de las complicaciones asociadas tanto a la enfermedad como a los procedimientos, así como diferentes controversias que rodean a la enfermedad y su tratamiento. El documento, realizado con la colaboración de expertos nacionales, permite establecer unas recomendaciones de carácter práctico, con su correspondiente nivel de evidencia y grado de recomendación, que facilitarán el diagnóstico, tratamiento y seguimiento de los pacientes con leucemia linfocítica crónica (AU)

Chronic lymphocytic leukemia is the most common chronic lymphoproliferative disorder in Spain. The clinical management of this entity varies widely. Currently, in Spain, there are no national consensus guidelines, such as those published in other countries, to guide the diagnosis and treatment of this malignancy and the use of prognostic scores. This article reviews the current scientific literature and addresses issues on the diagnosis of chronic lymphocytic leukemia, the spread of the disease, the presence of comorbidities, the classification of prognostic scores, the common treatment regimens stratified by risk factors, and the management of complications associated with both the disease and its treatment, as well as the various controversies related to this entity. This document was drafted with the collaboration of national experts and aims to establish practical guidelines with their corresponding levels of evidence and grades of recommendation to guide the diagnosis, treatment and follow-up of patients with chronic lymphocytic leukemia (AU)

Recommendations for the treatment of invasive fungal infection caused by filamentous fungi in the hematological patient

El tratamiento antifúngico del paciente hematológico ha alcanzado una gran complejidad con la llegada de nuevos antifúngicos y pruebas diagnósticas que han dado lugar a diferentes estrategias terapéuticas. La utilización del tratamiento más adecuado en cada caso es fundamental en infecciones con tanta mortalidad. La disponibilidad de recomendaciones como éstas, realizadas con la mejor evidencia por un amplio panel de 48 expertos, en las que se intenta responder a cuándo está indicado tratar y con qué hacerlo considerando diferentes aspectos del paciente (riesgo de infección fúngica, manifestaciones clínicas, galactomanano, TC de tórax y profilaxis realizada), puede ayudar a los clínicos a mejorar los resultados(AU)

Antifungal treatment in the hematological patient has reached a high complexity with the advent of new antifungals and diagnostic tests, which have resulted in different therapeutic strategies. The use of the most appropriate treatment in each case is essential in infections with such a high mortality. The availability of recommendations as those here reported based on the best evidence and developed by a large panel of 48 specialists aimed to answer when is indicated to treat and which agents should be used, considering different aspects of the patient (risk of fungal infection, clinical manifestations, galactomanann test, chest CT scan and previous prophylaxis) may help clinicians to improve the results(AU)

Update on viral infections in immunocompromised patients / Actualización de las infecciones víricas en los pacientes con inmunosupresión

Viral infections are one of the most frequent complications of oncohematologic and transplanted patients. Here we review some of the most interesting clinical publications of 2004 and 2005. A brief introduction of each virus or issue is given followed by a discussion of the related publications. In relation to CMV we reviewed: 1) the recommendations of the European Group for Blood and Marrow Transplantation for CMV management in stem-cell hematopoietic transplants (HSCT); 2) a meta-analysis that evaluated the efficacy of different strategies for the prevention of CMV in solid organ transplants; 3) the impact of CMV disease before HSCT in the outcome of the transplants. A recent publication found a relation between herpesvirus 6 infection and increased mortality. This is a novel finding, not previously described, that reinforces the importance of the so-called “indirect effects” of the beta-herpesvirus. In the largest study performed until now of influenza in HSCT recipients, early antiviral therapy with oseltamivir was more effective than rimantadine for both preventing progression from influenza-A upper respiratory infection to pneumonia and reducing influenza-A pneumonia mortality. The human metapneumovirus (hMPV) is a newly described virus identified in 2001. The epidemiological and clinical characteristics of hMPV respiratory infections were described in a large group of oncohematologic patients. A novel approach was published for the treatment of HLTV-1 infections based on the pathogenesis of this infection. Finally, an exciting paper from the Perugia group showed that cloning of pathogen-specific T-cells seems a promising approach in the management of certain infections after HSCT

Las infecciones víricas constituyen una de las complicaciones más frecuentes de los pacientes oncohematológicos y de los que reciben un trasplante. En este documento se revisan algunas de las publicaciones clínicas más interesantes de 2004 y 2005. Se ofrece una breve introducción de cada virus o proceso patológico, seguida de la discusión de las publicaciones relacionadas. En lo relativo al citomegalovirus (CMV), se han revisado: 1) las recomendaciones del European Group for Blood and Marrow Transplantation respecto al tratamiento del CMV en los trasplantes de células progenitoras hematopoyéticas (TPH); 2) un metaanálisis en el que se evaluó la eficacia de las distintas estrategias para la prevención de la infección por CMV en los pacientes intervenidos mediante trasplante de órganos sólidos; 3) la repercusión de la infección por CMV antes del TPH en lo relativo a la supervivencia del trasplante. En una publicación reciente se demuestra la existencia de una relación entre la infección por el virus herpes 6 y el incremento de la mortalidad. Este hallazgo es novedoso, en el sentido de que no se había descrito previamente, y refuerza la importancia de los denominados «efectos indirectos» de los virus herpes-beta. En el estudio más amplio efectuado hasta el momento del virus influenza en receptores de TPH, el tratamiento antivírico temprano con oseltamivir fue más efectivo que la administración de rimantadina tanto para la prevención de la progresión de la infección del tracto respiratorio superior por el virus de la gripe A hacia neumonía como en la reducción de la mortalidad por neumonía. El metaneumovirus humano (MNVh) fue descrito en 2001. Las características epidemiológicas y clínicas de las infecciones respiratorias causadas por MNVh fueron evaluadas en un grupo grande de pacientes oncohematológicos. Se ha propuesto un nuevo enfoque en el tratamiento de las infecciones causadas por el virus de la leucemia T humana del adulto tipo I, fundamentado en la patogenia de esta infección. Finalmente, en un artículo muy interesante del grupo de Perugia se demuestra que la clonación de linfocitos T con especificidad de patógeno parece constituir un abordaje prometedor en el tratamiento de ciertas infecciones asociadas al TCPH

Neumonía grave por virus respiratorio sincitial en paciente receptora de trasplante de progenitores hematopoyéticos / Severe respiratory syncytial virus pneumonia after blood progenitor cell transplantation

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