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Santa Maria Nuova, Italy

Gobbi P.G.,University of Pavia | Bergonzi M.,University of Pavia | Bassi E.,Radiologia | Merli F.,Unita Operativa di Ematologia | And 2 more authors.
Hematological Oncology | Year: 2013

We verified whether early resistance to treatment can be predicted in a subset of patients with very favourable, early stage Hodgkin lymphoma, treated with VBM (vinblastine, bleomycin and methotrexate) chemotherapy and involved-field radiotherapy, an effective combination with very low early and late toxicity. The relative tumour burden (rTB) was volumetrically measured from the staging computed tomography and analysed together with the parameters of pre-therapy evaluation in 61 patients enrolled into the protocol MH-1b of the Gruppo Italiano Studio Linfomi between 1996 and 2003. Early failure, codified by either less than complete remission (i.e. partial/null response or progression) or early relapse (within 12months from the end of therapy), was considered as clinical expression of resistance to treatment. Logistic regression and failure-free survival were the statistical tools for the analysis. The rTB demonstrated to be the best predictor of early failure, outperforming every other pre-treatment parameter, International Prognostic Score included. With a mean rTB value of 44.964±34.788cm3/m2 in the 53 patients successfully treated and of 130.185±63.993cm3/m2 in the eight with early treatment failure, the risk of resistance showed fivefold and 10-fold increases at rTB of 52.002 and 74.497cm3/m2, respectively. Only two patients relapsed more than 12months after the end of therapy; both had a high initial rTB. The rTB is the best predictor of resistance also in the subset of patients with very favourable, early stage disease. Safe rTB limits are proposed for successful administration of VBM chemotherapy plus involved-field radiotherapy. © 2012 John Wiley & Sons, Ltd.

Trecarichi E.M.,Catholic University of the Sacred Heart | Pagano L.,Catholic University of the Sacred Heart | Candoni A.,University of Udine | Pastore D.,Ematologia con Trapianto Azienda Ospedaliero Universitaria Policlinico | And 8 more authors.
Clinical Microbiology and Infection | Year: 2015

A prospective cohort study was conducted in nine hematology wards at tertiary care centres or at university hospitals located throughout Italy from January 2009 to December 2012. All of the cases of bacterial bloodstream infection (BBSI) occurring in adult patients with hematologic malignancies were included. A total of 668 bacterial isolates were recovered in 575 BBSI episodes. Overall, the susceptibility rates of Gram-negative bacteria were 59.1% to ceftazidime, 20.1% to ciprofloxacin, 79.1% to meropenem, 85.2% to amikacin, 69.2% to gentamicin and 69.8% to piperacillin/tazobactam. Resistance to third-generation cephalosporins was found in 98/265 (36.9%) of Enterobacteriaceae isolates. Among Klebsiella pneumoniae strains, 15/43 (34.9%) were resistant to carbapenems. Of 66 Pseudomonas aeruginosa isolates, 46 (69.7%) were multidrug resistant. Overall, the susceptibility rates of Gram-positive bacteria were 97.4% to vancomycin and 94.2% to teicoplanin. Among the monomicrobial cases of BBSI, the 21-day mortality rate was significantly higher for those caused by Gram-negative bacteria compared to those caused by Gram-positive bacteria (47/278, 16.9% vs. 12/212, 5.6%; p<0.001). Among Gram-negative bacteria, the mortality rate was significantly higher for BBSI caused by K.pneumoniae, P. aeruginosa, and Acinetobacter baumannii. Our results confirm the recently reported shift of prevalence from Gram-positive to Gram-negative bacteria as causative agents of BBSIs among patients with hematologic malignancies and highlight a worrisome increasing frequency in antimicrobial resistance among Gram-negative bacteria. © 2014 European Society of Clinical Microbiology and Infectious Diseases.

Moreau P.,University of Nantes | Richardson P.G.,Dana-Farber Cancer Institute | Cavo M.,University of Bologna | Orlowski R.Z.,University of Houston | And 3 more authors.
Blood | Year: 2012

Proteasome inhibition has emerged as an important therapeutic strategy in multiple myeloma (MM). Since the publication of the first phase 1 trials of bortezomib 10 years ago, this first-in-class proteasome inhibitor (PI) has contributed substantially to the observed improvement in survival in MM patients over the past decade. Although first approved as a single agent in the relapsed setting, bortezomib is now predominantly used in combination regimens. Furthermore, the standard twice-weekly schedule may be replaced by weekly infusion, especially when bortezomib is used as part of combination regimens in frontline therapy. Indeed, bortezomib is an established component of induction therapy for patients eligible or ineligible for autologous stem cell transplantation. Bortezomib has also been incorporated into conditioning regimens before autologous stem cell transplantation, as well as into post-ASCT consolidation therapy, and in the maintenance setting. In addition, a new route of bortezomib administration, subcutaneous infusion, has recently been approved. Recently, several new agents have been introduced into the clinic, including carfilzomib, marizomib, and MLN9708, and trials investigating these "secondgeneration" PIs in patients with relapsed/refractory MMs have demonstrated positive results. This review provides an overview of the role of PIs in the treatment of MM, focusing on developments over the past decade. © 2012 by The American Society of Hematology.

Niscola P.,Unita Operativa di Ematologia
Giornale italiano di nefrologia : organo ufficiale della Società italiana di nefrologia | Year: 2011

The treatment of pain in patients with impaired renal function may be problematic, especially when opioid drugs need to be used. In the presence of renal failure, significant changes occur in the metabolism and pharmacokinetics of these drugs, which can lead to adverse reactions due to the accumulation of parental compounds and active metabolites. This paper presents and discusses the available evidence concerning the optimal use of the most frequently employed opioid analgesics to treat pain in patients with renal impairment.

Palumbo A.,University of Turin | Bringhen S.,University of Turin | Bruno B.,University of Turin | Falcone A.P.,Unita Operativa di Ematologia Trapianto di Cellule Staminali | And 20 more authors.
Blood | Year: 2010

High-dose (200 mg/m2, MEL200) and intermediate-dose melphalan (100 mg/m2, MEL100) showed significant activity in myeloma. In a phase 3 study, 298 patients were randomly assigned to receive 2 autologous transplantations after conditioning with MEL200 or MEL100. Ninetysix of 149 (64%) completed MEL200 and 103 of 149 (69%) MEL100. Best response to MEL200 was: complete remission 22 of 149 (15%); partial remission 95 of 149 (64%), for an overall response rate of 79%. Best response to MEL100 was: complete remission 12 of 149 (8%); partial remission 95 of 149 (64%), for an overall response rate of 72%. Overall survival did not differ (P = .13); median progression-free survival (31.4 vs 26.2 months, P = .01), median time to progression (34.4 vs 27.0 months, P = .014) were longer in the MEL200. Treatment-related mortality was 3.1% in the MEL200 and 2.9% in the MEL100 group. Severe neutropenia and infections were marginally superior, whereas severe thrombocytopenia, mucositis, gastrointestinal adverse events, and the overall occurrence of at least 1 nonhematologic grade 3 or 4 adverse event were significantly higher in the MEL200 cohort.We conclude that MEL200 leads to longer remission duration and should be considered the standard conditioning regimen for autologous transplantation. This study was registered at www.clinicaltrials.gov as #NCT00950768. © 2010 by The American Society of Hematology.

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