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Brugiatelli M.,Struttura Complessa di Ematologia | Morabito F.,UOC Ematologia | Iannitto E.,Struttura Complessa di Ematologia Ospedale S. G. Moscati | Di Renzo N.,UOC Ematologia e Trapianti | And 3 more authors.
Expert Review of Hematology | Year: 2013

In chronic lymphocytic leukemia (CLL), the most prevalent lymphoid malignancy in western countries, patients have a median age at diagnosis of 72 years. In the last few years, there has been remarkable progress in understanding the biology of CLL, the detection of molecular prognostic factors and the development of more effective therapies. However, many of the milestone studies were conducted in populations that were considerably younger than the average age of the CLL population. Today, the challenge is to improve management of elderly patients. In this population, outcome of treatment with newer highly effective therapies is often compromised by comorbidities and poor performance status. Decision on how elderly patients should be treated is thus a complex issue. The management of these patients should rely on the development of risk-stratified treatment strategies based on the assessment of individual functional status and the biologic characteristics of CLL. New single agents with reduced toxic effects (i.e., inhibitors of BCR signalling) that have achieved promising results in Phase I/II studies when available should modify the paradigm of the treatment of elderly patients with CLL. © 2013 Informa UK Ltd.

Filosa A.,Uod Centro Per Le Microcitemie | Vitrano A.,University of Palermo | Rigano P.,Cervello | Calvaruso G.,Cervello | And 15 more authors.
Blood Cells, Molecules, and Diseases | Year: 2013

Transfusion and iron chelation treatment have significantly reduced morbidity and improved survival of patients with thalassemia major. However, cardiac disease continues to be the most common cause of death. We report the left-ventricular ejection fraction, determined by echocardiography, in one hundred sixty-eight patients with thalassemia major followed for at least 5. years who received continuous monotherapy with deferoxamine (N=108) or deferiprone (N=60). The statistical analysis, using the generalized estimating equations model, indicated that the group treated with deferiprone had a significantly better left-ventricular ejection fraction than did those treated with deferoxamine (coefficient 0.97; 95% CI 0.37; 1.6, p=0.002).The heart may be particularly sensitive to iron-induced mitochondrial damage because of the large number of mitochondria and its low level of antioxidants. Deferiprone, because of its lower molecular weight, might cross into heart mitochondria more efficiently, improving their activity and, thereby, myocardial cell function. Our findings indicate that the long-term administration of deferiprone significantly enhances left-ventricular function over time in comparison with deferoxamine treatment. However, because of limitations related to the design of this study, these findings should be confirmed in a prospective, randomized clinical trial. © 2013 Elsevier Inc.

Bassan R.,UOC Ematologia | Spinelli O.,Hematology and Bone Marrow Transplant Unit
Current Hematologic Malignancy Reports | Year: 2015

Almost 90 % of children and 50 % of adults with acute lymphoblastic leukemia (ALL) are cured by modern treatment regimens, with significant variations due to several disease- and host-related characteristics. The attainment of an early remission and the avoidance of relapse and treatment-related mortality are the fundamental therapeutic steps. In remission patients, the assessment of the disease response to early intensive therapy through the detection and monitoring of minimal residual disease (MRD) can accurately refine the individual prognosis and is increasingly used to support a risk-oriented treatment strategy. In this way, only the patients with an unfavorable MRD response are preferably selected for allogeneic stem cell transplantation, irrespective of their clinical risk class. This choice spares transplant-related toxicities to MRD responsive cases. Further advancement is expected by integrating the MRD analysis with improved pediatric-type regimens and novel targeting agents for ALL subsets at higher risk of relapse. © 2015, Springer Science+Business Media New York.

Fragasso A.,Unita Semplice di Ematologia | Ciancio A.,Unita Semplice di Ematologia | Mannarella C.,Unita Semplice di Ematologia | Gaudiano C.,Unita Semplice di Ematologia | And 9 more authors.
European Journal of Internal Medicine | Year: 2011

Background: Cardiac complications secondary to iron overload remain a significant matter in patients with transfusion dependent anemias. Patients and methods: To evaluate cardiac siderosis, Magnetic resonance imaging T2* (MRI T2*) was performed in 3 cohorts of transfusion dependent patients: 99 with thalassemia major (TM), 20 with thalassemia intermedia (TI), and 10 with acquired anemias (AA). Serum ferritin was measured and all patients underwent echocardiographic evaluation. Results: In TM patients cardiac T2* pathologic values (below 20 ms) were found in 37 patients. Serum ferritin was negatively associated with age (r = -0.32, p = 0.001) and weakly with T2* values (r = -0.19, p = 0.057). A positive correlation was found between T2* and LVEF (r = 0.27, p = 0.006). Out of 37 patients with T2* < 20 ms, 18 (48%) had serum ferritin values < 1000 ng/ml. In TI cohort, 3 patients had cardiac T2* pathologic values. In AA cohort, pathologic T2* values were found in 2 patients, who received 234 and 199 PRBC units, respectively, and were both on chelation therapy (in one patient ferritin value was 399 ng/ml). T2* values were negatively associated, but not significantly, with the number of PRBC transfused (r = -0.53, p = 0.07). Conclusion: In our experience, 37% of TM patients had a myocardial iron overload assessed by MRI T2*; this value is higher than in TI patients. Serum ferritin measurement was a poor predictor of myocardial siderosis. In patients with AA, more than 200 PRBC units transfused were required to induce cardiac hemosiderosis, in spite of chelation therapy and, in one patient, of normal ferritin values. © 2010 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Pagano L.,Catholic University of the Sacred Heart | Verga L.,University of Milan Bicocca | Martino B.,Azienda Ospedaliera Bianchi Melacrino Morelli | Mitra M.E.,Policlinico di Palermo | And 11 more authors.
The Journal of antimicrobial chemotherapy | Year: 2014

OBJECTIVES: To investigate the incidence, treatment and outcome of breakthrough invasive fungal infections (IFIs) in adult acute myeloid leukaemia (AML) patients after posaconazole prophylaxis.METHODS: From January 2010 to April 2012, all consecutive patients with newly diagnosed AML were prospectively registered at 33 participating Italian centres. All cases of IFIs occurring within 30 days after the end of the first induction chemotherapy were recorded. The strategy of antifungal treatment (empirical, pre-emptive or targeted) and the drugs used were analysed. ClinicalTrials.gov code: NCT01315925.RESULTS: In total, 1192 patients with newly diagnosed AML were enrolled in the study, of whom 510 received posaconazole prophylaxis and were included in the present analysis. Of these patients, 140 (27%) needed systemic antifungal treatment. Among the 127 evaluable cases, an empirical approach was utilized in 102 patients (80%), a pre-emptive approach in 19 patients (15%) and targeted therapy in 6 patients (5%). Only five patients died of IFIs (three in the empirical group and two in the targeted group; 4%). A critical review of IFI diagnoses at 30 days demonstrated that among the patients treated empirically, ∼30% were not affected by IFIs but rather only by fever of unidentified origin. A comparison between the empirical and the pre-emptive groups showed no significant differences regarding the attributable and overall mortalities.CONCLUSIONS: This study confirms that posaconazole prophylaxis reduces the incidence of breakthrough IFIs and does not modify the efficacy of subsequent systemic antifungal treatment, regardless of the approach (empirical or pre-emptive) or the antifungal drug used. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

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