Lacerra G.,CNR Institute of Genetics and Biophysics Adriano Buzzati Traverso |
Prezioso R.,CNR Institute of Genetics and Biophysics Adriano Buzzati Traverso |
Musollino G.,CNR Institute of Genetics and Biophysics Adriano Buzzati Traverso |
Piluso G.,The Second University of Naples |
And 4 more authors.
European Journal of Haematology | Year: 2013
Objectives: To characterize the molecular basis of a β-thalassemia defect in subjects with mild microcytosis associated with normal Hb A2 and increased levels of Hb F. Methods: Six subjects from three apparently unrelated families from Campania (southern Italy) have been investigated using DNA restriction analysis, inverse PCR, cloning, sequencing, multiplex ligation-dependent probe amplification (MLPA), quantitative real-time PCR, and gap-PCR. Results: We have identified a novel 55-kb β-globin gene cluster deletion in three unrelated families: the Italian Gγ(Aγδβ)°-thalassemia. This deletion removes most of the β-globin cluster. The 5′ breakpoint was within the Aγ-globin exon 2, and the 3′ breakpoint was within a 160-bp palindrome: the breakpoint-flanking regions present a microhomology (5′-TGGG-3′) that, together with the palindromic structure, may have contributed to the recombination. Conclusions: Large deletions of β-globin gene cluster are usually found in single families. Here, we report about the novel Italian Gγ(Aγδβ)°-thalassemia we have found in three families. Twenty years ago, the characterization of the first family was challenging, whereas that of the other families has taken advantage of nowadays techniques. The relatively high frequency of this novel deletion in southern Italy suggests that it should be tested, together with the Sicilian (δβ)°-thalassemia, in Italian and Mediterranean families with microcytosis, normal Hb A2, and increased Hb F levels.© 2013 John Wiley & Sons A/S.
PubMed | SODc Ematologia, University of Rome La Sapienza, UO Ematologia e Centro Trapianti, AO S Maria di Terni and 14 more.
Type: Journal Article | Journal: Leukemia | Year: 2016
This phase 2 trial evaluated three low-dose intensity subcutaneous bortezomib-based treatments in patients 75 years with newly diagnosed multiple myeloma (MM). Patients received subcutaneous bortezomib plus oral prednisone (VP, N=51) or VP plus cyclophosphamide (VCP, N=51) or VP plus melphalan (VMP, N=50), followed by bortezomib maintenance, and half of the patients were frail. Response rate was 64% with VP, 67% with VCP and 86% with VMP, and very good partial response rate or better was 26%, 28.5% and 49%, respectively. Median progression-free survival was 14.0, 15.2 and 17.1 months, and 2-year OS was 60%, 70% and 76% in VP, VCP, VMP, respectively. At least one drug-related grade 3 non-hematologic adverse event (AE) occurred in 22% of VP, 37% of VCP and 33% of VMP patients; the discontinuation rate for AEs was 12%, 14% and 20%, and the 6-month rate of toxicity-related deaths was 4%, 4% and 8%, respectively. The most common grade 3 AEs included infections (8-20%), and constitutional (10-14%) and cardiovascular events (4-12%); peripheral neuropathy was limited (4-6%). Bortezomib maintenance was effective and feasible. VP, VCP and VMP regimens demonstrated no substantial difference. Yet, toxicity was higher with VMP, suggesting that a two-drug combination followed by maintenance should be preferred in frail patients.
PubMed | University of Rome La Sapienza, Ospedali Riuniti di Ancona, University of Turin, Hematology Oncology and 25 more.
Type: | Journal: European journal of cancer (Oxford, England : 1990) | Year: 2016
Recently, encouraging results in terms of safety and efficacy have been obtained using bendamustine-rituximab (BR) in untreated chronic lymphocytic leukaemia (CLL) patients enrolled in a phase II study. Here, we report a retrospective international multicenter study of CLL patients treated with BR as front-line therapy. The cohort included 279 patients with progressive CLL from 33 centers (29 Italian, 3 Israeli and 1 German) who received at least 1 cycle of BR as first-line treatment during the 2008-2014 period. The primary objective of this study was to evaluate the efficacy and safety of BR administered as front-line therapy, outside of controlled clinical trials. Median age was 70 years (range, 43-86 years); 62.4% were males and 35.8% had Binet stage C. Forty-two patients (15.2%) were unfit (cumulative illness rating scale [CIRS] score 7), and 140 (50.2%) had creatinine clearance 70ml/min. Fluorescent in situ hybridisation analysis, available for 192 cases, showed that 21 (10.9%) had del11q and 18 (9.4%) del17p. The overall response rate (ORR) was 86.4%, with a complete remissionrate of 28%. Patients with del17p had an ORR of 66.7%. After median follow-up of 24 months, the 2-year progression-free survival (PFS) was 69.9%; CIRS 7, immunoglobulin heavy-chain variable-region (IGHV) unmutated status, del17p and BR dose intensity <80% were independently associated with shorter PFS. Grade III or IV neutropenia, thrombocytopenia, and anaemia were observed in 25.9%, 15.4%, and 15.1% of patients, respectively. Twenty-four patients (8.6%) had severe infections. BR is also an effective and safe regimen for untreated CLL patients, outside of controlled clinical trials.
PubMed | University Hospital Brno and Medical Faculty, Azienda Ospedaliera Pugliese Ciaccio, University of Barcelona and UOC Ematologia
Type: | Journal: American journal of hematology | Year: 2017
Rai and Binet staging systems are important to predict the outcome of patients with CLL but do not reflect the biologic diversity of the disease nor predict response to therapy, which ultimately shape patients outcome. We devised a biomarkers-only CLL prognostic system, based on the two most important prognostic parameters in CLL (i.e. IGHV mutational status and FISH cytogenetics), separating three different risk groups: (1) low-risk (mutated IGHV+no adverse FISH cytogenetics [del(17p), del(11q)]); (2) intermediate-risk (either mutated IGHV or adverse FISH cytogenetics); and (3) high-risk (unmutated IGHV+adverse FISH cytogenetics. In 524 unselected subjects with CLL, the 10-year overall survival was 82% (95% CI 76-88%), 52% (45-62%), and 27% (17-42%) for the low-, intermediate-, and high-risk groups, respectively. Patients with low-risk comprised around 50% of the series and had a life expectancy comparable to the general population. The prognostic model was fully validated in two independent cohorts, including 417 patients representative of general CLL population and 337 patients with Binet stage A CLL. The model had a similar discriminatory value as the CLL-IPI. Moreover, it applied to all patients with CLL independently of age, and separated patients with different risk within Rai or Binet clinical stages. The biomarkers-only CLL prognostic system presented here simplifies the CLL-IPI and could be useful in daily practice and to stratify patients in clinical trials. This article is protected by copyright. All rights reserved.
PubMed | Ematologia, UOC Ematologia, University Cattolica Sacro Cuore, Presidio and 3 more.
Type: Journal Article | Journal: European journal of haematology | Year: 2015
Deferasirox (DFX) is an orally administered iron chelator approved for use in patients with transfusion-dependent iron overload due to myelodysplastic syndromes (MDS). The safety and efficacy of DFX has been explored in clinical trial settings, but there is little data on unselected patients with MDS. The aim of this study was to retrospectively evaluate the safety, compliance, efficacy and effect on haematopoiesis of DFX in a large real-world MDS population. One hundred and eighteen patients with transfusion-dependent MDS were treated with DFX across 11 centres in Italy. Serum ferritin levels, haematological response, dosing, adverse events and transfusion dependence were recorded at baseline, 3, 6, 12 and 24 months following initiation of treatment. DFX reduced mean serum ferritin levels from 1790 to 1140 ng/mL (P < 0.001), with 7.1% of patients achieving transfusion independence. Significant haematological improvement was seen in erythroid (17.6%), platelet (5.9%) and neutrophil counts (7.1%). Adverse events were reported in 47.5% of patients, including gastrointestinal and renal toxicity. Regression analysis showed that higher starting doses of DFX are associated with transfusion independence at 24 months. DFX is a safe, effective treatment for transfusion-dependent MDS that can lead to transfusion independence and haematological improvement in a subset of patients.
PubMed | U.O.C. Cardiochirurgia, U.O.C. Cardiologia and U.O.C. Ematologia
Type: Case Reports | Journal: Giornale italiano di cardiologia (2006) | Year: 2016
Central venous catheters (CVC) are commonly used in clinical practice. Although long-term complications are uncommon, catheter-related right atrial thrombosis is a rare but potentially life-threatening one. The optimal management is still controversial. We report the case of a young woman affected by Hodgkin lymphoma with CVC-related right atrial thrombosis diagnosed during routine echocardiography. After initial anticoagulation treatment, she complicated with pulmonary embolism, and the mass was surgically removed via a minimally invasive approach with right minithoracotomy access. Surgery was well tolerated, without complications and with prompt recovery. This case confirms how CVC can lead to thrombosis in the right atrium and how this complication can rapidly deteriorate. Moreover, the possible treatment options for the successful management of this complication are discussed, along with the available literature, showing the advantages of a minimally invasive approach.
PubMed | U.O.S. di Talassemia P.O. Giovanni Paolo II Sciacca, U.O. Genetica ed Immunologia Pediatrica, Centro Microcitemia, U.O. Talassemia Ospedale Garibaldi and 10 more.
Type: Journal Article | Journal: British journal of haematology | Year: 2016
In the last few decades, the life expectancy of regularly transfused -thalassaemia major (TM) patients has dramatically improved following the introduction of safe transfusion practices, iron chelation therapy, aggressive treatment of infections and improved management of cardiac complications. How such changes, especially those attributed to the introduction of iron chelation therapy, improved the survival of TM patients to approach those with -thalassaemia intermedia (TI) remains unknown. Three hundred and seventy-nine patients with TM (n=284, dead 40) and TI (n=95, dead 13) were followed retrospectively since birth until 30 June 2015 or death. Kaplan-Meir curves showed statistically significant differences in TM and TI survival (P<00001) before the introduction of iron chelation in 1965, which were no longer apparent after that date (P=0086), reducing the Hazard Ratio of death in TM compared to TI from 68 [95% confidence interval (CI) 26-175] before 1965 to 28 (95% CI 08-92). These findings suggest that, in the era of iron chelation therapy and improved survival for TM, the major-intermedia dichotomy needs to be revisited alongside future directions in general management and prevention for both conditions.