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Defina M.,University of Siena | Ippoliti M.,University of Siena | Gozzetti A.,University of Siena | Abruzzese E.,University of Rome Tor Vergata | And 11 more authors.
Cancer | Year: 2012

Background: Compared with imatinib, nilotinib is a potent breakpoint cluster region/v-abl Abelson murine leukemia viral oncogene (bcr-abl) kinase inhibitor, and it induces higher rate and rapid complete cytogenetic response (CCyR), yet no clinical data are available regarding its efficacy against chronic myeloid leukemia (CML) stem cells. Earlier studies demonstrated that clusters of differentiation 34-positive, Philadelphia chromosome-positive (CD34+Ph+) cells are detectable in about 45% of patients with CML, despite being on long-term imatinib therapy and having achieved sustained CCyR. Methods: CD34+ cells from bone marrow of de novo CML patients in the chronic phase (n = 24) treated with nilotinib (median duration of therapy, 22 months) were isolated and scored for BCR-ABL by fluorescent in situ hybridization (FISH) analysis. Similar analysis was also performed in 5 de novo CML chronic phase patients who achieved CCyR within 3 months of nilotinib therapy. Results: FISH evaluation of a median of 100 CD34+ nuclei per patient revealed that only 1 of 20 (5%) evaluable patients showed residual Ph+ progenitor cells. In this patient, just 1 of 140 (0.7%) CD34 + interphase nuclei was found to be positive for BCR-ABL. Surprisingly, no CD34+Ph+ cells were found even in those 5 patients evaluated after 3 months of nilotinib treatment. Conclusions: This study assessed for the first time the persistence of CD34+Ph + cells during nilotinib first-line treatment. Preliminary results showed that in patients in CCyR, even after short-term nilotinib therapy, residual leukemic progenitors are very rarely detected compared with imatinib-treated CCyR patients. It is yet to be determined if these findings will have an impact in the path to a cure of CML with tyrosine kinase inhibitors. Cancer 2012. © 2012 American Cancer Society. In patients with chronic myeloid leukemia who are treated with first-line nilotinib and are in complete cytogenetic response, residual clusters of differentiation 34-positive, Philadelphia chromosome-positive (CD34+/Ph+) stem cells are rarely detected. This may suggest that the fast inhibitory activity displayed by nilotinib on the bulk of chronic myeloid leukemia affects progenitor cells as well. © 2012 American Cancer Society.

Vecchio S.,Cardiac Catheterization Laboratory | Varani E.,Cardiac Catheterization Laboratory | Nuzzo A.,Santa Maria Delle Croci Hospital | Balducelli M.,Cardiac Catheterization Laboratory | And 4 more authors.
Minerva Cardioangiologica | Year: 2014

Percutaneous mechanical thrombectomy (PMT) for treatment of clinically significant pulmonary embolism (PE) has been shown to be technically feasible and effective, aiming at thrombus resolution without increase in major bleeding. Despite its success, use of PMT in clinical practise has not become widespread, because it is challenging. Among several devices proposed, Angiojet rheolytic thrombectomy (ART) appears as the most effective and easy-to-use. We present the case of a 69-year-old woman who developed acute intermediate-risk PE, with right ventricular dysfunction and major myocardial necrosis, who was successfully treated by ART. The peculiarities of the case, toghether with the principles, tecnique and tips and tricks of ART, its effectiveness and potential complications are discussed.

Placci A.,Santa Maria Delle Croci Hospital | Lovato L.,University of Bologna | Bonvicini M.,University of Bologna
BMJ Case Reports | Year: 2014

We describe the case of an 83-year-old asymptomatic man followed in our centre. Transoesophageal echocardiography disclosed congenitally corrected transposition of great arteries (CCTGA) with no associated anomalies and only mild aortic regurgitation. Cardiac MR confirmed the diagnosis and revealed preserved systemic ventricle systolic function with a normal perfusional pathway. This report is a demonstration that CCTGA without associated anomalies can reach older life in an asymptomatic condition. This is the oldest asymptomatic living patient with CCTGA ever described. Copyright 2014 BMJ Publishing Group. All rights reserved.

Montillo M.,Niguarda caGranda Hospital | Tedeschi A.,Niguarda caGranda Hospital | Petrizzi V.B.,Oncology and Hematology Unit | Ricci F.,Niguarda caGranda Hospital | And 10 more authors.
Blood | Year: 2011

Although combination regimens have improved outcomes over monotherapy in chronic lymphocytic leukemia (CLL), patients eventually relapse. Combined fludarabine, cyclophosphamide, and monoclonal anti-CD52 antibody alemtuzumab (FCC) provided synergistic cytotoxicity with effective clearing of minimal residual disease. This phase 2 study determined FCC efficacy and safety in relapsed/ refractory CD52 + B-CLL after ≥ 1 line of treatment. From January 2005 through June 2008, up to 6 courses of oral fludarabine 40 mg/m2 per day, oral cyclophosphamide 250 mg/m 2 per day, and subcutaneous alemtuzumab (Mab-Campath) 10 mg (increased to 20 mg after first 10-patient cohort) were administered days 1 to 3 every 28 days. The primary objective was overall response rate (ORR); secondary objectives included response duration, time to disease progression, and safety and tolerability. ORR was 67% in 43 patients; 30% achieved complete response. ORR significantly improved with 1 versus ≥ 2 prior therapies (P ∇ .018), and without versus with previous monoclonal antibody treatment (P ∇ .003). Median progression-free survival was 24.4 months, not reached in patients achieving complete response. Median overall survival was 33.6 months. Myelosuppression was the most common adverse event, with a low percentage of cytomegalovirus reactivations and manageable infections. However, close vigilance of opportunistic infections is warranted. FCC provides effective immunotherapy in relapsed/refractory CLL, including in patients with poor-risk prognostic factors. © 2011 by The American Society of Hematology.

Rocca A.,Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori | Bravaccini S.,Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori | Scarpi E.,Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori | Mangia A.,National Cancer Research Center | And 17 more authors.
Breast Cancer Research and Treatment | Year: 2014

There are no validated predictors of benefit from anthracyclines. We compared cyclophosphamide, methotrexate, 5-fluorouracil (CMF), and epirubicin in different sequences with CMF alone in a phase III trial on operable breast cancers. Outcomes were analyzed in relation to tumor biological profiles to identify potential predictors of the efficacy of different treatments/drug combinations. Patients with N- or 1-3N+ tumors, were randomized to receive (a) epirubicin (4 cycles) followed by CMF (4 cycles); (b) CMF (4 cycles) followed by epirubicin (4 cycles), or (c) CMF (6 cycles) alone. Immunohistochemical assessments of estrogen (ER) and progesterone (PgR) receptors, HER2 and Ki67 were available for 705 patients (arm A/B/C: 276/269/160). Prognostic and predictive relevance was analyzed by log-rank tests and Cox models. Ki67 > 20 % and absent/low expression of ER and PgR were associated with worsen disease-free (DFS) and overall survival (OS). In patients with triple negative tumors (ER-, PgR-, HER2-), epirubicin-containing regimens yielded better DFS (HR 0.33, 95 % CI 0.17-0.62, P = 0.0007) and OS (HR 0.24, 95 % CI 0.10-0.57, P = 0.001) compared with CMF alone, whereas no differences were found in patients with HER2-positive (HER2+, ER-, PgR-) subtype. Treatment by subtype interaction (HER2-positive vs. others) was significant for DFS (χ 2 = 6.72, P = 0.009). In triple unfavorable (ER-, PgR-, Ki67 > 20 %) tumors, the use of epirubicin yielded better DFS (HR 0.45,95 % CI 0.26-0.78, P = 0.005) and OS (HR 0.30, 95 % CI 0.15-0.63, P = 0.001). Epirubicin-containing regimens seem to be superior to CMF alone in patients with highly proliferating, triple negative or triple unfavorable tumors. © 2013 Springer Science+Business Media.

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