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Find video protocols related to scientific articles indexed in Pubmed.
Celebrating 40 years of progress in bone marrow transplantation: a report from the 40th Annual Meeting of the European Society for Blood and Marrow Transplantation.
Future Microbiol
PUBLISHED: 11-19-2014
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ABSTRACT? The European Society for Blood and Marrow Transplantation was established in 1974 to enable scientists and physicians involved in clinical bone marrow transplantation to share their experience and develop cooperative studies. The organization celebrated its 40th anniversary with a meeting that considered hematopoietic stem cell transplantation not as a standalone procedure, but as part of a complex therapeutic program managed by a multidisciplinary professional team. The role of antifungal prophylaxis, emerging resistance in Aspergillus, the management of mucormycosis and new guidelines on antifungal therapy were among the topics discussed by the physicians, nurses, allied health professionals and scientists attending the 40th Annual Meeting of the European Society for Blood and Marrow Transplantation.
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Systemic antifungal treatment after posaconazole prophylaxis: results from the SEIFEM 2010-C survey.
J. Antimicrob. Chemother.
PUBLISHED: 06-19-2014
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To investigate the incidence, treatment and outcome of breakthrough invasive fungal infections (IFIs) in adult acute myeloid leukaemia (AML) patients after posaconazole prophylaxis.
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Primary prophylaxis of invasive fungal diseases in allogeneic stem cell transplantation: revised recommendations from a consensus process by Gruppo Italiano Trapianto Midollo Osseo (GITMO).
Biol. Blood Marrow Transplant.
PUBLISHED: 02-21-2014
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This document updates and expands the recommendations on primary prophylaxis of invasive fungal diseases (IFD) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients, published in 2009 by the Gruppo Italiano Trapianto Midollo Osseo (GITMO). A consensus process was undertaken to describe and evaluate current information and practice regarding risk stratification and primary antifungal prophylaxis during the pre-engraftment and postengraftment phases after allo-HSCT. The revised recommendations were based on the evaluation of recent literature including a large, prospective, multicenter epidemiological study of allo-HSCT recipients conducted among the GITMO transplantation centers during the period of 2008 to 2010. It is intended as a guide for the identification of types and phases of transplantation at low, standard, and high risk for IFD, according to the underlying disease, transplantation, and post-transplantation factors. The risk stratification was the critical determinant of the primary antifungal approach for allo-HSCT recipients.
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Genetic PTX3 deficiency and aspergillosis in stem-cell transplantation.
N. Engl. J. Med.
PUBLISHED: 01-31-2014
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The soluble pattern-recognition receptor known as long pentraxin 3 (PTX3) has a nonredundant role in antifungal immunity. The contribution of single-nucleotide polymorphisms (SNPs) in PTX3 to the development of invasive aspergillosis is unknown.
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Characterization of specific immune responses to different Aspergillus antigens during the course of invasive Aspergillosis in hematologic patients.
PLoS ONE
PUBLISHED: 01-01-2013
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Several studies in mouse model of invasive aspergillosis (IA) and in healthy donors have shown that different Aspergillus antigens may stimulate different adaptive immune responses. However, the occurrence of Aspergillus-specific T cells have not yet been reported in patients with the disease. In patients with IA, we have investigated during the infection: a) whether and how specific T-cell responses to different Aspergillus antigens occur and develop; b) which antigens elicit the highest frequencies of protective immune responses and, c) whether such protective T cells could be expanded ex-vivo. Forty hematologic patients have been studied, including 22 patients with IA and 18 controls. Specific T cells producing IL-10, IFN-?, IL-4 and IL-17A have been characterized through enzyme linked immunospot and cytokine secretion assays on 88 peripheral blood (PB) samples, by using the following recombinant antigens: GEL1p, CRF1p, PEP1p, SOD1p, ?1-3glucan, ?1-3glucan, galactomannan. Specific T cells were expanded through short term culture. Aspergillus-specific T cells producing non-protective interleukin-10 (IL-10) and protective interferon-gamma (IFN-?) have been detected to all the antigens only in IA patients. Lower numbers of specific T cells producing IL-4 and IL-17A have also been shown. Protective T cells targeted predominantly Aspergillus cell wall antigens, tended to increase during the IA course and to be associated with a better clinical outcome. Aspergillus-specific T cells could be successfully generated from the PB of 8 out of 8 patients with IA and included cytotoxic subsets able to lyse Aspergillus hyphae. Aspergillus specific T-cell responses contribute to the clearance of the pathogen in immunosuppressed patients with IA and Aspergillus cell wall antigens are those mainly targeted by protective immune responses. Cytotoxic specific T cells can be expanded from immunosuppressed patients even during the infection by using the above mentioned antigens. These findings may be exploited for immunotherapeutic purposes in patients with IA.
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Incidence of acute myeloid leukemia after breast cancer.
Mediterr J Hematol Infect Dis
PUBLISHED: 12-07-2011
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Breast cancer is the most frequent cancer among women and the leading cause of death among middle-aged women. Early detection by mammography screening and improvement of therapeutic options have increased breast cancer survival rates, with the consequence that late side effects of cancer treatment become increasingly important. In particular, patients treated with adjuvant chemotherapy regimens, commonly including alkylating agents and anthracyclines, are at increased risk of developing leukemia, further enhanced by the use of radiotherapy. In the last few years also the use of growth factors seems to increase the risk of secondary leukemia. The purpose of this review is to update epidemiology of therapy-related myeloid neoplasms occurring in breast cancer patients.
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Temsirolimus, an mTOR inhibitor, in combination with lower-dose clofarabine as salvage therapy for older patients with acute myeloid leukaemia: results of a phase II GIMEMA study (AML-1107).
Br. J. Haematol.
PUBLISHED: 11-15-2011
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The mammalian target of rapamycin (mTOR) signalling pathway has emerged as an important therapeutic target for acute myeloid leukaemia (AML). This study assessed the combination of temsirolimus, an mTOR inhibitor, and lower-dose clofarabine as salvage therapy in older patients with AML. Induction consisted of clofarabine 20mg/m(2) on days 1-5 and temsirolimus 25mg (flat dose) on days 1, 8 and 15. Patients achieving complete remission with (CR) or without (CRi) full haematological recovery could receive monthly temsirolimus maintenance. In 53 evaluable patients, the overall remission rate (ORR) was 21% (8% CR, 13% CRi). Median disease-free survival was 3·5months, and median overall survival was 4months (9·1months for responders). The most common non-haematological severe adverse events included infection (48%), febrile neutropenia (34%) and transaminitis (11%). The 30-d all-cause induction mortality was 13%. Laboratory data from 25 patients demonstrated that a >50%in vivo inhibition of S6 ribosomal protein phosphorylation was highly correlated with response rate (75% with inhibition versus 0% without inhibition; P=0·0001), suggesting that targeting the mTOR pathway is clinically relevant. The acceptable safety profile and the predictive value of target inhibition encourage further investigation of this novel regimen.
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Uncommon yeast infections in hematological patients: from diagnosis to treatment.
Expert Rev Anti Infect Ther
PUBLISHED: 10-28-2011
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Invasive fungal diseases have been recognized with increasing frequency as major pathogens in patients with cancer over the past few decades, as a result of new and more aggressive anticancer treatments and supportive care, and this has been especially reported for patients suffering from hematological malignancies. In these settings, typically uncommon yeasts and filamentous fungi have recently emerged as significant human pathogens, frequently as breakthrough infections in patients receiving empirical antifungal therapy or antifungal prophylaxis and with reported high crude mortality rates. The aim of this article is to discuss certain aspects of the approach to invasive fungal diseases due to uncommon yeasts (e.g., Trichosporon spp., Blastomyces spp. and Cryptococcus spp.) in patients with hematological malignancies, focusing on epidemiology, diagnosis, treatment outcomes and the role of novel antifungal drugs (i.e., new triazoles and echinocandins).
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Diagnosis of invasive aspergillosis by a commercial real-time PCR assay for Aspergillus DNA in bronchoalveolar lavage fluid samples from high-risk patients compared to a galactomannan enzyme immunoassay.
J. Clin. Microbiol.
PUBLISHED: 10-19-2011
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Culture-independent molecular techniques such as real-time PCRs offer the potential for early diagnosis of invasive aspergillosis (IA), thereby reducing the disease-associated mortality rate. PCR-based testing is presently excluded from disease-defining consensus criteria due to lack of standardization and clinical validation. A single-center prospective study was conducted to investigate the performance of the commercially available MycAssay Aspergillus test for detecting Aspergillus DNA in patients with suspicion of IA. To this end, a total of 158 bronchoalveolar lavage (BAL) fluid specimens that were consecutively collected from hematology (n = 68) and intensive care unit (n = 90) patients were examined. Sixteen of 17 (94.1%) specimens from patients with proven/probable IA were MycAssay positive, and 15 of these 16 patients were also positive by an "in-house" PCR assay. A total of 139 of 141 (98.6%) specimens from patients without proven/probable IA were MycAssay negative. Fifteen of 16 (94.1%) MycAssay-positive patients were also positive for BAL fluid galactomannan (GM) at an index cutoff of ?1.0 (index range, 1.1 to 8.3), as were 3 patients without IA but with pulmonary fusariosis. Interestingly, in seven of the PCR-positive BAL specimens that tested culture positive for Aspergillus species, cycle threshold values were earlier than those of specimens with a culture-negative result. In conclusion, the MycAssay Aspergillus PCR appears to be a sensitive and specific molecular test for the diagnosis of IA, and its performance is comparable to that of the GM assay. However, more large studies are necessary to firmly establish its clinical utility in high-risk settings.
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Update on invasive fungal disease.
Future Microbiol
PUBLISHED: 10-01-2011
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One of the highlights of the antifungal sessions at the ECCMID-ICC congress was the presentation of the first European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guideline for diagnostic and management for Candida diseases. Experts also discussed specific aspects of the management of invasive fungal disease in the intensive care unit and in hematological malignancy. Data from new clinical studies and from real life experience of clinical use of antifungal therapy were also presented and discussed.
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Impaired bactericidal and fungicidal activities of neutrophils in patients with myelodysplastic syndrome.
Leuk. Res.
PUBLISHED: 08-31-2011
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Infections are a major cause of morbidity and mortality in patients with myelodysplastic syndrome (MDS) due to quantitative and qualitative granulocytic defects. We evaluated the in vitro bactericidal and fungicidal activities of neutrophils isolated from MDS. With comparison to those from healthy individuals, MDS neutrophils following infection showed a significantly reduced killing activity against Escherichia coli at 8 (p=0.002), 24 (p<0.0001), 48 (p=0.0005), and 72 h (p=0.0264), against Lactococcus lactis at 24 (p=0.0002), 48 (p<0.0001), and 72 h (p<0.0001), and more against Candida albicans at 8 (p=0.0003), 24 (p<0.0001), 48 (p<0.0001), and 72 h (p<0.0001). Our data show that MDS neutrophils have an impaired microbicidal function, which might account for the high susceptibility to infections of MDS patients.
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Uncommon mold infections in hematological patients: epidemiology, diagnosis and treatment.
Expert Rev Anti Infect Ther
PUBLISHED: 08-04-2011
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Invasive fungal diseases continue to be an important cause of morbidity and mortality in immunosuppressed patients. This is of particular interest, since the progress we made in the treatment of underlying malignancies has led to an increase of the number of persons at high risk. During the last few years, several changes in clinical practice in hematology (new immunosuppressants, hematopoietic stem cell transplants) have influenced the epidemiology of invasive fungal diseases; in particular, cases due to some uncommon etiologic agents are being increasingly reported, making it even more urgent to reconsider differential diagnoses in high-risk patients. A better understanding of epidemiology, risk factors and prognosis appears to be crucial to analyze prevention and diagnostic strategies, as well as to guarantee an early and adequate treatment.
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Similarities and differences between therapy-related and elderly acute myeloid leukemia.
Mediterr J Hematol Infect Dis
PUBLISHED: 07-07-2011
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Acute myeloid leukemia (AML) is a clonal disorder of the hematopoietic stem cell, typical of the elderly, with a median age of over 60 years at diagnosis. In AML, older age is one of the strongest independent adverse prognostic factor, associated with decreased complete response rate, worse disease-free and overall survival, with highest rates of treatment related mortality, resistant disease and relapse, compared to younger patients. Outcomes are compromised in older patients not only by increased comorbidities and susceptibility to toxicity from therapy, but it is now recognized that elderly AML has peculiar biologic characteristics with a negative impact on treatment response.In older individuals prolonged exposure to environmental carcinogens may be the basis for similarities to therapy-related myeloid malignancies (t-MN), which result from toxic effects of previous cytotoxic treatments on hematopoietic stem cells. Age is itself a risk factor for t-MN, which are more frequent in elderly patients, where also a shorter latency between treatment of primary tumor and t-MN has been reported. t-MN following chemotherapy with alkylating agents and elderly AML frequently present MDS-related cytogenetic abnormalities, including complex or monosomal karyotype, and a myelodysplastic phase preceding the diagnosis of overt leukemia. Similarly, t-MN and elderly-AML share common molecular abnormalities, such as reduced frequency of NPM1, FLT3 and CEBPA mutations and increased MDR1 expression.Given the unfavorable prognosis of elderly and t-MN and the similar clinical and molecular aspects, this is a promising field for implementation of new treatment protocols including alternative biological drugs.
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The use and efficacy of empirical versus pre-emptive therapy in the management of fungal infections: the HEMA e-Chart Project.
Haematologica
PUBLISHED: 05-12-2011
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Neutropenic patients with persistent fever despite antibiotic therapy are managed with empirical or pre-emptive antifungal therapy. The aim of the present study was to evaluate the current clinical use and efficacy of these two approaches in patients with high risk hematologic conditions.
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Primary plasma cell leukemia in the era of new drugs: has something changed?
Crit. Rev. Oncol. Hematol.
PUBLISHED: 01-15-2011
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Primary plasma cell leukemia (PPCL) is a rare and aggressive variant of multiple myeloma. This disease is associated with a very poor prognosis, and unfortunately it has not significantly improved during the last three decades. Autologous stem cell transplantation is generally recommended in eligible patients, but survival in transplanted PPCL patients is significantly lower than that of multiple myeloma. Recent preliminary data indicate that new drugs, in particular lenalidomide and bortezomib, could significantly improve the clinical outcome of PPCL, increasing response rate and duration, as well as survival. In this review we report an updated literature analysis about the current therapeutic scenario of PPCL, with a particular focus on the use of novel agents.
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Primary plasma cell leukemia followed by testicular plasmacytoma.
Int. J. Hematol.
PUBLISHED: 01-13-2011
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Plasma cell leukemia (PCL) is a highly aggressive plasma cell disease characterized by a poor prognosis and a low response rate to conventional therapy. Herein, we describe a 69-year-old patient with primary PCL, developing testicular disease while in complete hematological remission, following by muscle involvement and peritoneal dissemination.
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Risk assessment and prognostic factors for mould-related diseases in immunocompromised patients.
J. Antimicrob. Chemother.
PUBLISHED: 01-05-2011
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Invasive fungal diseases are important causes of morbidity and mortality in immunocompromised patients. Patients with haematological malignancies and solid cancers, as well as those with allogeneic haematopoietic stem cell and solid organ transplants, are at high risk of developing such an infection. Many fungi can cause invasive disease, with Aspergillus spp. and Candida spp. being the prevalent fungal pathogens infecting susceptible patients. During the past few years, rare moulds (for example Zygomycetes and Fusarium spp.) have come into focus as the cause of devastating clinical disease. This review aims to analyse environmental factors and parameters related to impairment of the immune system that are thought to favour the onset of invasive mould infections. Some moulds are quite common among all categories of patients, while others appear to be limited to a given subset of patients, such as allogeneic haematopoietic stem cell or solid organ transplant recipients. In addition to an exploration of factors that predispose patients to the acquisition of an invasive mould infection, prognostic factors that help to predict the eventual outcome of these infections are identified.
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Invasive aspergillosis in acute leukemias: old and new risk factors and epidemiological trends.
Med. Mycol.
PUBLISHED: 08-26-2010
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In recent years, there has been increased interest in the development of prophylactic and diagnostic tools for patients at high risk for invasive aspergillosis (IA), resulting in a significant investment of human, technical, and economic resources. There are several classic risk factors for the development of IA, including neutropenia, graft-versus-host disease, and corticosteroid use. However, despite having similar risk profiles, only a subset of at-risk individuals will develop this fungal complication. At present, there is a significant expansion of the classically defined high-risk group due to the ageing of the general population, the intensification of treatment strategies, and the introduction of new drugs into clinical practice (e.g., monoclonal antibodies, TNF inhibitors). Therefore, an improved categorization of patients would be useful in order to better target available resources and avoid the risk of potential overtreatment and toxicities.
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Adherence to international guidelines for the treatment of invasive aspergillosis in acute myeloid leukaemia: feasibility and utility (SEIFEM-2008B study).
J. Antimicrob. Chemother.
PUBLISHED: 07-16-2010
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In order to assess physicians compliance with international guidelines for the targeted treatment of invasive aspergillosis, 136 patients with acute myeloid leukaemia and proven/probable invasive aspergillosis were analysed.
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Promoter methylation of DAPK1, E-cadherin and thrombospondin-1 in de novo and therapy-related myeloid neoplasms.
Blood Cells Mol. Dis.
PUBLISHED: 03-20-2010
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DNA methylation is one of the major epigenetic changes in human cancers, leading to silencing of tumor suppressor genes, with a pathogenetic role in tumor development and progression in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Methylation of key promoter regions, induced by cytotoxic therapy together with complex genetic changes, is important in the biology of therapy-related myeloid neoplasms (t-MN). We were interested in the characterization of the methylation pattern of AML and MDS de novo and therapy-related. We studied 385 patients (179 females, 206 males), of a median age of 66 years (range 16-98 years). There were 105 MDS, 208 de novo AML and 72 t-MN (45 MDS and 27 AML). Using a methylation-specific PCR, we studied the promoter methylation status of E-cadherin (CDH1), TSP1 and DAP-Kinase 1. These genes have been shown to be involved in the malignant transformation, interfering with angiogenesis, interaction with micro-environment, apoptosis and xenobiotic detoxification. We found no associations between promoter hypermethylation and gender or age at the time of initial diagnosis. In patients with MDS, there were no associations between hypermethylation and clinical characteristics, including IPSS score, WHO classification and cytogenetics. DAPK1 was more frequently methylated in t-MDS/AML when compared to de novo MDS and AML (39% vs 15.3% and 24.4%, p=0.0001), while methylation of CDH1 was similar in t-MDS/AML and AML (51% and 53.4%), but less frequent in de novo MDS (29%) (p=0.003). In the t-MDS/AML group, we found that the methylation pattern appeared to be related to the primary tumor, with DAPK1 more frequently methylated in patients with a previous lymphoproliferative disease (75% vs 32%, p=0.006). On the other hand, methylation of CDH1 was associated to radiotherapy for the primary malignancy (84.5% vs 38%, p=0.003). TSP1 hypermethylation was rare and not characteristic of t-MDS/AML. In 177 patients studied for concurrent methylation of several promoters, t-MN and AML de novo were significantly more frequently hypermethylated in 2 or more promoter regions than de novo MDS (20% vs 12.4%, p<0.001). Chemotherapy and individual genetic predisposition have a role in t-MDS/AML development, the identification of specific epigenetic modifications may explain complexity and genomic instability of these diseases and give the basis for targeted-therapy. The significant association with previous malignancy subtypes may underlie a likely susceptibility to methylation of specific targets and a role for constitutional epimutations as predisposing factors for the development of therapy-related myeloid neoplasm.
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Current therapeutic approaches to fungal infections in immunocompromised hematological patients.
Blood Rev.
PUBLISHED: 01-06-2010
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Invasive fungal infections are significant causes of morbidity and mortality in patients with hematological malignancies. Patients with acute myeloid leukemia and those who have undergone allogeneic hematopoietic stem cell transplantation are at especially high risk. Various fungal agents are responsible for this complication, but Aspergillus spp. and Candida spp. are the most frequently isolated micro-organisms; less commonly, infections could be caused by Zygomycetes or other rare molds or yeasts. Several new systemically-administered antifungal agents have been approved for clinical use since 2001; these agents include liposomal amphotericin B, voriconazole, caspofungin, and posaconazole, and they represent a major advance in antifungal therapy and have improved the prognosis of patients with hematological malignancies. This review focuses on therapeutic aspects of the management of fungal infections in hematological patients.
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Clinical aspects and therapy of sporadic burkitt lymphoma.
Mediterr J Hematol Infect Dis
PUBLISHED: 11-20-2009
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Burkitts lymphoma is a highly aggressive mature B-cell neoplasm consisting of endemic, sporadic, and immunodeficiency-associated variants, sharing many morphologic and immunophenotypic features. It is characterized by a high proliferation rate and propensity for extranodal sites such as gastrointestinal tract and reproductive organs. Brief-duration, high-intensity chemotherapy regimens including aggressive central nervous system prophylaxis have had remarkable success in the treatment of this disease in the sporadic form, with very high complete remission rate and overall survival in adults. Although Burkitts lymphoma is extremely chemosensitive, biologically targeted therapies should be developed, because current treatment options are suboptimal for patients with poor prognostic features or with relapsed disease.
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Incidence and susceptibility to therapy-related myeloid neoplasms.
Chem. Biol. Interact.
PUBLISHED: 09-04-2009
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Therapy-related myeloid neoplasms (t-MN) include acute myeloid leukemias and myelodysplastic syndromes arising in patients who have been treated with chemotherapy, radiation therapy, immunosuppressive agents or after documented exposure to environmental carcinogen. t-MN are defined according to the primary treatment and the corresponding genetic and molecular lesions. Chromosome(s) 7 and/or 5 monosomies or deletions are typical of alkylating agent-induced AML, while balanced translocations involving chromosome bands 11q23 and 21q22 are associated to preceeding therapy with DNA-topoisomerase II inhibitors. Antimetabolites, and in particular the immunosuppressive agents azathioprine and fludarabine, have also been recently associated to t-MN. Leukemias developing after benzene exposure are similar to t-MN and are characterized by chromosomal aberrations, which have been also observed among otherwise healthy benzene-exposed workers. Individual predisposing factors, including polymorphisms of detoxification and DNA-repair enzymes have been identified. Two genetic variants in key metabolizing enzymes, myeloperoxidase and NAD(P)H:quinone oxidoreductase, have been shown to influence susceptibility to benzene hematotoxicity. Combination of polymorphisms impairing detoxification and DNA repair may significantly increase therapy-related myeloid neoplasm risk. Among hematological malignancies, long-term survivors of Hodgkins lymphoma are exposed to an increased t-MN risk, particularly when receiving MOPP-based and escalated-BEACOPP regimens, and when alkylators are combined to radiotherapy. Patients with lymphoma are at highest risk if total body irradiation followed by autologous stem cell transplantation is used as rescue or consolidation. The addition of granulocyte-colony stimulating factor (G-CSF) and radiotherapy plays a significant role in t-MN following treatment of childhood acute lymphoblastic leukemia. In solid tumors, treatment for breast cancer and germ-cell tumors has been associated with a 1-5% lifetime risk of t-MN.
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Epigenetic changes in therapy-related MDS/AML.
Chem. Biol. Interact.
PUBLISHED: 09-03-2009
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Therapy-related Myelodysplastic Syndromes/Acute Myeloid Leukemias (t-MDS/AML) are one of the most compelling long term adverse events occurring in cancer survivors treated with chemo-radiotherapy regimes. Beside several well-described genetic lesions, a growing amount of data suggests that abnormalities in DNA methylation profile contribute to multistep secondary leukemogenesis. Two distinct alterations of normal DNA methylation patterns may occur in cancer: a global hypomethylation resulting in chromosomal instability and loss of genetic integrity, and promoter specific DNA hypermethylation which leads to silencing of tumor suppressor genes. Cytotoxic drugs and radiation have been shown to affect tissue DNA methylation profile. Radiation is able to induce a stable DNA hypomethylation in both target and bystander tissues. Gene promoter methylation is a common finding in t-MDS/AML and has been associated to a shorter latency period from the treatment of the primary tumor. Among the studied genes, p15 methylation correlated to monosomy/deletion of chromosome 7q, suggesting that it could be a relevant event in alkylating agent-induced leukemogenesis. We found frequent methylation of DAPK in the t-MDS/AML group, especially in patients with a previous lymphoproliferative disease. In patients studied for concurrent methylation of several promoters, t-MDS/AML were significantly more frequently hypermethylated in 2 or more promoter regions than de novo MDS or AML suggesting that promoter hypermethylation of genes involved in cell cycle control, apoptosis and DNA repair pathways is a frequent finding in t-MDS/AML and may contribute to secondary leukemogenesis. However, how the epigenetic machinery is disrupted after chemo/radiotherapy and during secondary carcinogenesis is still unknown, warranting further studies.
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Polymorphisms of detoxification and DNA repair enzymes in myelodyplastic syndromes.
Leuk. Res.
PUBLISHED: 05-29-2009
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The genetic background may modify the individuals risk of developing cancer. We performed a case-control study to test the impact of genomic polymorphisms of 9 genes involved in xenobiotics detoxification and DNA repair in myelodysplastic syndromes (MDS). Frequencies of polymorphic variants of RAD51, XRCC3, NQO1, GSTA1, GSTM1, GSTT1, CYP3A4 and XPD enzymes were similar in patients and controls. On the other hand, the GSTP1-105Val allele was associated to an increased risk of MDS (O.R. 1.66; p=0.04) and to higher probability of overall survival in the low/intermediate-1 IPSS risk group (p=0.008). The GSTP1-Ile105Val polymorphism is likely to influence MDS risk and prognosis.
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ZYGOMYCOSIS: current approaches to management of patients with haematological malignancies.
Br. J. Haematol.
PUBLISHED: 05-18-2009
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Zygomycosis is an invasive infection that can occur particularly in patients with haematological malignancy. The causative fungi are members of the order Mucorales, and individual species within this group require a high level of laboratory skill to be identified. Zygomycosis can present as rhinocerebral, pulmonary, or disseminated disease, with a rapid clinical course. The optimal management of these cases requires early diagnosis, aggressive antifungal therapy and, when possible, surgical debridement. Founded on clinical experience, but without the benefit of comparative studies, liposomal amphotericin B has become the therapeutic agent of choice. Posaconazole is an orally administered triazole with a demonstrated in vitro and in vivo activity against most Zygomycetes that is comparable to that of amphotericin B. Studies on salvage therapy with posaconazole have yielded promising results, and successful case reports are also available. As an adjuvant approach, iron chelation with deferasirox has shown promising results, although clinical experience is still limited.
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Immature platelet fraction (IPF) in hospitalized patients with neutrophilia and suspected bacterial infection.
J. Infect.
PUBLISHED: 03-19-2009
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Neutrophilia is frequently in hospitalized patients, so a screening test for infections would be very useful. The immature platelet fraction (IPF) is provided by the automated blood analyzer XE 2100 (Sysmex, Kobe, Japan) as a proportional value of the total optical platelet count [IPF%; an absolute count of immature platelets can also be obtained (AIPC)] to indicate the rate of platelet production. IPF could help to identify the aetiology of thrombocytopenia and to recognize the increased bone marrow activity as occurred during the course of infectious disease.
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Factors associated with mortality in bacteremic patients with hematologic malignancies.
Diagn. Microbiol. Infect. Dis.
PUBLISHED: 02-17-2009
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We conducted a retrospective cohort study to identify risk factors for mortality in a large cohort of hematologic patients with bacteremia. From 2000 through 2005, bacteremia was diagnosed in 217 patients with hematologic malignancies. The infections were caused only by Gram-positive organisms in 57.1% (124/217) cases and only by Gram-negative bacteria in 37.8% (82/217); the remaining 5.1% (11/217) were polymicrobial. The overall 30-day mortality rate was 20.3% (44/217). In multivariate analysis, significant predictors of mortality were prolonged neutropenia (P < 0.001), acute renal failure (P = 0.002), nosocomial bacteremia (P = 0.009), age >55 years (P = 0.007), and monomicrobial bacteremia due to antibiotic-resistant Gram-negative bacteria (P = 0.009). Reducing fatal outcomes associated with bacteremia in patients with hematologic malignancies is a challenge, and the emergence of resistance to the antimicrobials widely used in this setting is of great concern. Future infection trends must be carefully monitored and treatment guidelines adjusted accordingly.
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Incidence and clinical impact of extended-spectrum-beta-lactamase (ESBL) production and fluoroquinolone resistance in bloodstream infections caused by Escherichia coli in patients with hematological malignancies.
J. Infect.
PUBLISHED: 02-06-2009
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To identify risk factors for mortality in patients suffering from hematological malignancies with concurrent bacteremia caused by Escherichia coli. Particular attention was focused on defining the impact of extended-spectrum-beta-lactamase (ESBL) production and fluoroquinolone resistance by the bacterial isolates on mortality.
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Derivation and validation of a scoring system to identify patients with bacteremia and hematological malignancies at higher risk for mortality.
PLoS ONE
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The aim of this study was to develop and validate a reliable clinical prediction rule that could be employed to identify patients at higher likelihood of mortality among those with hematological malignancies (HMs) and bacterial bloodstream infections (BBSIs).
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Blastic plasmacytoid dendritic cell neoplasm with leukemic presentation: an Italian multicenter study.
Haematologica
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The objective of this study was to evaluate the clinical features, prognostic factors, and efficacy of treatments in patients with blastic plasmacytoid dendritic cell neoplasm with a leukemic presentation at onset of the disease. In order to do this, a retrospective multicenter study was performed from 2005-2011 in 28 Italian hematology divisions in which 43 cases were collected. Forty-one patients received an induction therapy, consisting of an acute myeloid leukemia-type regimen in 26 patients (60%) and acute lymphoid leukemia/lymphoma-type regimen in 15 patients (35%). Six patients (14%) underwent allogeneic hematopoietic stem cell transplantation. Seventeen patients (41%) achieved a complete remission: seven after acute myeloid leukemia-type treatment and 10 after an acute lymphoid leukemia/lymphoma-type regimen, with a significant advantage for acute lymphoid leukemia/lymphoma-type chemotherapy (P=0.02). Relapse occurred in six of the 17 patients (35%) who achieved complete remission, more frequently after acute lymphoid leukemia/lymphoma-type chemotherapy. The median overall survival was 8.7 months (range, 0.2-32.9). The patients treated with an acute myeloid leukemia-type regimen had an overall survival of 7.1 months (range, 0.2-19.5), whereas that of the patients receiving acute lymphoid leukemia/lymphoma-type chemotherapy was 12.3 months (range, 1-32.9) (P=0.02). The median overall survival of the allogeneic hematopoietic stem cell transplant recipients was 22.7 months (range, 12-32.9), and these patients had a significant survival advantage compared to the non-transplanted patients (median 7.1 months, 0.2-21.3; P=0.03). In conclusion, blastic plasmacytoid dendritic cell neoplasm with bone-marrow involvement is an aggressive subtype of high-risk acute leukemia. The rarity of this disease does not enable prospective clinical trials to identify the better therapeutic strategy, which, at present, is based on clinicians experience.
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A hematology consensus agreement on antifungal strategies for neutropenic patients with hematological malignancies and stem cell transplant recipients.
Hematol Oncol
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In the attempt to establish key therapy definitions and provide shared approaches to invasive fungal diseases in neutropenic patients, trials of empiric, preeemptive and targeted antifungal therapy (EAT, PAT and TAT) were reviewed, and a Consensus Development Conference Project was convened. The Expert-Panel concurred that all antifungal treatments, including EAT, should always follow an adequate diagnostic strategy and that the standard definition of PAT may be misleading: being PAT guided by the results of a diagnostic work-up, it should better be termed diagnostic-driven antifungal therapy (DDAT). The Expert-Panel agreed that radiological findings alone are insufficient for the choice of a TAT and that the identification of the etiologic pathogen is needed. The Consensus Agreement proceeded identifying which clinical and microbiological findings were sufficient to start a DDAT and which were not. Finally, an algorithm to rationalize the choice of antifungal drugs on the basis of clinical manifestations, antifungal prophylaxis, instrumental and laboratory findings was drawn up. Copyright © 2012 John Wiley & Sons, Ltd.
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Diagnosis and treatment of mucormycosis in patients with hematological malignancies: guidelines from the 3rd European Conference on Infections in Leukemia (ECIL 3).
Haematologica
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Mucormycosis is an emerging cause of infectious morbidity and mortality in patients with hematologic malignancies. However, there are no recommendations to guide diagnosis and management. The European Conference on Infections in Leukemia assigned experts in hematology and infectious diseases to develop evidence-based recommendations for the diagnosis and treatment of mucormycosis. The guidelines were developed using the evidence criteria set forth by the American Infectious Diseases Society and the key recommendations are summarized here. In the absence of validated biomarkers, the diagnosis of mucormycosis relies on histology and/or detection of the organism by culture from involved sites with identification of the isolate at the species level (no grading). Antifungal chemotherapy, control of the underlying predisposing condition, and surgery are the cornerstones of management (level A II). Options for first-line chemotherapy of mucormycosis include liposomal amphotericin B and amphotericin B lipid complex (level B II). Posaconazole and combination therapy of liposomal amphotericin B or amphotericin B lipid complex with caspofungin are the options for second line-treatment (level B II). Surgery is recommended for rhinocerebral and skin and soft tissue disease (level A II). Reversal of underlying risk factors (diabetes control, reversal of neutropenia, discontinuation/taper of glucocorticosteroids, reduction of immunosuppressants, discontinuation of deferroxamine) is important in the treatment of mucormycosis (level A II). The duration of antifungal chemotherapy is not defined but guided by the resolution of all associated symptoms and findings (no grading). Maintenance therapy/secondary prophylaxis must be considered in persistently immunocompromised patients (no grading).
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Risks for infection in patients with myelodysplasia and acute leukemia.
Curr. Opin. Infect. Dis.
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The aim of the present review is to analyze the main parameters that may influence the onset of bacterial, fungal and viral infections in patients with myelodysplastic syndromes, acute myeloid leukemia and acute lymphoid leukemia.
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Outcome of therapy-related myeloid neoplasms treated with azacitidine.
J Hematol Oncol
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Therapy-related myeloid neoplasms (t-MN), including myelodysplastic syndromes and acute myeloid leukemia (t-MDS and t-AML) are associated to clinical and biologic unfavorable prognostic features, including high levels of DNA methylation.
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Systemic granulomatous reaction secondary to treatment of bladder cancer with bacillus calmette-guerin.
Mediterr J Hematol Infect Dis
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Intravesical instillation of Bacillus Calmette-Guérin is the elective treatment for transitional cell and in situ bladder carcinoma. Severe complications occur very seldom, but must be known and promptly recognized. We describe the case of a 48-year-old man, treated with chemo-immunotherapy ten years before for a follicular lymphoma, who developed a systemic granulomatous reaction after his twelfth intravescical BCG instillation for bladder cancer.
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A prospective, multicentre survey on antifungal therapy in neutropenic paediatric haematology patients.
Mycoses
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Invasive fungal infections are a frequent complication after intensive chemotherapy. The aims of this prospective study were to describe the use of antifungal therapy and to report which strategy was routinely adopted to guide the introduction of antifungal therapy. A total of 321 febrile episodes in 160 paediatric patients affected by acute leukaemia or non-Hodgkin-lymphoma were investigated. Antifungal therapy was used in 100 of 321 febrile episodes (31%), and classified as empiric in 73 episodes, diagnostic-driven in 25 episodes and targeted in 2 episodes. Switching to a second-line antifungal therapy was needed in 28 of 100 episodes (28%) and was classified as empiric in 10 episodes (36%), diagnostic-driven in 17 episodes (61%) and targeted in 1 episode (4%). In 9 of 28 episodes (32%), switching to a third-line antifungal therapy was performed and was classified as empiric in 2 episodes (22%), diagnostic-driven in 6 episodes (67%) and targeted in 1 episode (11%). Invasive fungal infections was reported in 23 of 100 episodes: confirmed in 4 episodes, probable in 8 episodes, and possible in 11 episodes. Attributable mortality was 2.8%. Antifungal therapy was still used mostly empirically, whereas as fever persisted, its modification was guided by a diagnostic-driven approach.
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First case of breakthrough pneumonia due to Aspergillus nomius in a patient with acute myeloid leukemia.
Med. Mycol.
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We report the first known case of a breakthrough pulmonary infection caused by Aspergillus nomius in an acute myeloid leukemia patient receiving caspofungin therapy. The isolate was identified using matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS) and sequencing-based methods. The organism was found to be fully susceptible, in vitro, to echinocandin antifungal agents.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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