Showing papers by "Mario Boccadoro published in 2006"
TL;DR: Oral MPT is an effective first-line treatment for elderly patients with multiple myeloma and anticoagulant prophylaxis reduces frequency of thrombosis.
792 citations
TL;DR: Corticosteroid may avoid discontinuation for hepatotoxicity of the most effective anti-CML therapy and may avoid discontinued treatment with imatinib.
Abstract: BACKGROUND: Imatinib can induce severe hepatotoxicity, in 1-5% of CML patients, many of whom need permanent imatinib discontinuation. DESIGN AND RESULTS: We report 5 CML patients who developed grade 3-4 hepatotoxicity after 2-8 months in imatinib. Different aetiologies of liver damage were ruled out and toxicity recurred in 2 patients with further attempts at low dose imatinib. In all patients prednisone or methylprednisolone at 25- 40 mg/day resolved hepatotoxicity in 3-8 weeks and allowed imatinib to be resumed at full doses. Corticosteroid were tapered off in 3-5 months without hepatotoxicity recurrence. CONCLUSIONS: Corticosteroid may avoid discontinuation for hepatotoxicity of the most effective anti-CML therapy.
257 citations
TL;DR: Bortezomib was approved in 2003 by the FDA for the treatment of patients with multiple myeloma who had received at least two prior therapies and demonstrated disease progression on the last therapy; its application was expanded recently for second-line treatment.
Abstract: Bortezomib is a protease inhibitor and is the first compound in this drug class to be used in clinical practice, with trials demonstrating efficacy in patients with relapsed/refractory multiple myeloma Mature clinical data on the efficacy of bortezomib in solid tumors are not yet available, but early clinical data indicate this could be a promising drug for the treatment of advanced solid tumors This Review summarizes the principal clinical trials of bortezomib and discusses its efficacy in solid and hematologic tumors Proteasome inhibition represents a new anticancer approach, with the potential effect of arresting tumor growth, metastasis and angiogenesis through the activation of multiple mechanisms Bortezomib is a biologically active agent, producing predictable, dose-related and reversible proteasome inhibition; it has shown antitumor activity in various malignancies and is the first proteasome inhibitor to be used in clinical practice Several trials demonstrated that bortezomib is relatively well tolerated, causing manageable nonhematologic and hematologic toxicity The drug was approved in 2003 by the FDA for the treatment of patients with multiple myeloma who had received at least two prior therapies and demonstrated disease progression on the last therapy; its application was expanded recently for second-line treatment This article summarizes the principal clinical trials of bortezomib and discusses its efficacy in solid and hematologic tumors
111 citations
TL;DR: Bortezomib has demonstrated significant antitumor activity as a single agent in refractory and/or relapsed MM, with a significantly longer survival than with dexamethasone and in combination therapy, patient responses suggest the possibility of chemosensitization and synergy.
Abstract: Despite intensive therapy, multiple myeloma (MM) remains an incurable disease, and novel treatment approaches are therefore needed to improve outcome. Bortezomib is the first proteasome inhibitor to be approved by the U.S. Food and Drug Administration (FDA) and the European Agency for the Evaluation of Medicinal Products for the treatment of refractory or relapsed MM following the failure of at least two prior lines of therapy. Recently, it also received approval from the FDA for use as a second-line agent. An expert panel of hematologists met at the Ninth Congress of the European Hematology Association to review clinical data and experience in the treatment of MM with bortezomib, including bortezomib-based combination therapy. The conclusions of this expert panel, together with updated clinical data from the American Society of Hematology 46th Annual Meeting, provide a practical update on the use of bortezomib in MM. Bortezomib has demonstrated significant antitumor activity as a single agent in refractory and/or relapsed MM, with a significantly longer survival than with dexamethasone (1-year overall survival rate of 80% vs. 66%) and a 78% longer median time to progression. In combination therapy, patient responses suggest the possibility of chemosensitization and synergy. Furthermore, bortezomib does not appear to have an adverse effect on subsequent stem cell therapy. Bortezomib is well tolerated; most side effects are only mild to moderate and are manageable. Information is given on the practical management of the most common adverse events, including peripheral neuropathy and thrombocytopenia, and the use of bortezomib in renal and hepatic impairment.
104 citations
TL;DR: No significant differences in toxicity and response rates were seen between patients treated with bortezomib plus steroids and bortzomib alone, and after a median follow-up of 6 months, progression free survival was 6 months.
Abstract: We retrospectively evaluated the efficacy of bortezomib in 23 patients with multiple myeloma who had relapsed after allografting. Bortezomib was given as single agent to 9 patients (39%) and in combination with steroids in the other 14 (61%). Major toxicities were thrombocytopenia (10/23, 43%) and peripheral neuropathy (12/23, 52%). The overall response rate was 61% (14/23), including 22% (5/23) immunofixation-negative complete remissions. No significant differences in toxicity and response rates were seen between patients treated with bortezomib plus steroids and bortezomib alone. After a median follow-up of 6 months, progression free survival was 6 months. Twenty-one patients are alive, two and five in continuous very good partial and complete remissions, respectively.
63 citations
TL;DR: The results indicate that rituximab is active against residual MCL cells and suggest that molecularly tailored maintenance therapy needs to be investigated in clinical trials.
56 citations
TL;DR: M(i.v.)PT is an effective regimen, which can overcome resistance to thalidomide plus prednisone in advanced myeloma with acceptable toxicity.
Abstract: :
Objectives: Thalidomide combined with conventional chemotherapies including oral melphalan shows significant anti-myeloma activity. To address this issue, feasibility and efficacy of a three drug combination consisting of intravenous (i.v.) melphalan, thalidomide and prednisone [M(i.v.)PT] was evaluated in advanced myeloma patients. Patients and methods: Twenty-four advanced myeloma patients were treated with multiple cycles of a regimen consisting of low dose i.v. melphalan (20 mg/m2) at d 1, thalidomide at the dose of 50–100 mg/d given continuously and oral prednisone at the planned dose of 50 mg/d every other day. Intravenous melphalan was administered every fourth month. Median time from diagnosis was 40 months (range: 8–144 months). Fifteen patients (66%) had previously been treated with a combination of thalidomide and dexamethasone or with thalidomide alone. Results: Overall, on an intent-to treat basis, 14 patients responded: three achieved near complete remission (nCR), seven achieved partial response (PR), four minimal response (MR). Six patients showed stable disease (SD) and four-disease progression. Interestingly, of five patients who had previously progressed while on thalidomide and prednisone, one reached nCR, two PR and one MR. After a median follow up of 14 months, median progression free survival was 9 months. Response duration was longer than that induced by the previous line of treatment in eight patients (33%). Thalidomide-associated toxicity mainly consisted of constipation, tingling and sedation. Conclusions: M(i.v.)PT is an effective regimen, which can overcome resistance to thalidomide plus prednisone in advanced myeloma with acceptable toxicity.
56 citations
TL;DR: Circadian variations within the hemostatic and fibrinolytic systems, with emphasis on venous thromboembolism, are found in mouse blood coagulation.
44 citations
TL;DR: R-MP induced a high proportion of responses and appeared to overcome the poor prognosis of patients with chromosome 13q deletion, andoxicity was manageable, and occurred more frequently during early cycles.
43 citations
TL;DR: Bortezomib, with its unique mechanism of action and demonstrated clinical efficacy and safety, should be considered as standard, early treatment in patients with relapsed multiple myeloma, especially after first relapse, experts concluded.
Abstract: Cure for multiple myeloma is rare; the success of treatment is measured by response, and length of remissions and survival. Initial treatment for patients young and fit enough is high-dose chemotherap
34 citations
TL;DR: A case in which KS concomitantly occurred with CMV reactivation after a non‐myeloablative allogeneic HCT and presented with skin lesions, but not visceral involvement is described, indicating viral reactivation of the recipient's primary infection.
Abstract: Human herpesvirus 8 (HHV-8) is causally associated with Kaposi's sarcoma (KS). KS is most frequently observed in HIV patients and in solid organ transplant recipients. The role of HHV-8 in allogeneic haematopoietic cell transplantation (HCT) remains to be determined. Here we describe a case in which KS concomitantly occurred with CMV reactivation after a non-myeloablative allogeneic HCT and presented with skin lesions, but not visceral involvement. Skin biopsy confirmed the diagnosis and ruled out graft versus host disease or disease recurrence. Molecular findings indicated viral reactivation of the recipient's primary infection. Tumour lesions completely receded when immunosuppression was tapered. Prevalence studies in donors and recipients are needed to determine the clinical impact of HHV-8 in HCT.
TL;DR: Melphalan/bortezomib/thalidomide/dexamethasone showed encouraging antimyeloma activity in patients with advanced-stage myeloma.
Abstract: Background Bortezomib and thalidomide have shown synergy with melphalan and dexamethasone. We used this 4-drug combination as conditioning before autologous hematopoietic cell infusions. Patients and Methods Twenty-six patients with advanced-stage myeloma were treated with melphalan 50 mg/m 2 and bortezomib 1.3 mg/m 2 on days −6 and −3 in association with thalidomide 200 mg and dexamethasone 20 mg on days −6 through −3, followed by hematopoietic cell support on day 0. Results Nonhematologic toxicities included pneumonia, febrile neutropenia, and peripheral neuropathy. All patients had undergone autologous transplantation at diagnosis, and 13 patients (50%) underwent an additional transplantation at relapse. Responses occurred in 17 of 26 patients (65%), including 1 complete remission, 3 near complete remissions (12%), and 2 very good partial remissions (8%). Response rate was higher than that induced by the previous line of treatment in 12 patients (46%). Conclusion Melphalan/bortezomib/thalidomide/dexamethasone showed encouraging antimyeloma activity in patients with advanced-stage myeloma.
TL;DR: It is concluded that bortezomib alone may induce high quality responses as third line salvage therapy with acceptable toxicity in a significant proportion of homogeneously pre-treated myeloma patients with progressive disease after autologous transplantation and thalidomide.
TL;DR: MEL200 resulted in a significantly higher near complete response rate than MEL100, but partial response was 80% versus 71%, respectively (p=0.011), and gastrointestinal toxicities were similar in both groups.
TL;DR: The results indicate that NLABR-positive clones are persistent populations phenotypically related to follicular lymphoma (FL), which suggests the existence of a FL-related clonal expansion of undetermined significance, which might be either a premalignant or a nonmalignant counterpart of FL.
TL;DR: In vitro studies at DF concentrations achievable in vivo were conducted to evaluate effects on growth factors critical for tumor neovascularization and pathways regulating bioavailability of extracellular matrix (ECM)-resident growth factors, and suggest that DF can perturb bioavailability, expression and/or function of diverse positive regulators of neo-angiogenesis.
TL;DR: These include monoclonal antibodies, agents that target mammalian target of rapamycin, histone acetylation, heat-shock proteins, growth factor signalling cascades, oncogenes, signal transducer and activators of the transcription pathway, Akt pathway and MAPK pathway.
Abstract: Multiple myeloma remains a fatal neoplasm and new treatments are urgently needed. In recent years, advances in understanding the molecular pathophysiology of myeloma and the mechanisms of drug resistance led to the development of several novel agents. The drugs with the most available clinical data are thalidomide, bortezomib and lenalidomide. Impressive results obtained with these agents - both in relapsed disease and in newly diagnosed patients - have significantly improved the outcome of myeloma patients. Several other new targeted agents are presently under investigation. These include monoclonal antibodies, agents that target mammalian target of rapamycin, histone acetylation, heat-shock proteins, growth factor signalling cascades, oncogenes, signal transducer and activators of the transcription pathway, Akt pathway and MAPK pathway. Their mechanisms of action, the available knowledge on their efficacy, safety and possible future clinical application are reviewed.
TL;DR: The use of DHAP/alemtuzumab appears useful to re-induce disease remission in relapsed/refractory B-CLL patients, however, the addition of autograft was not usually feasible and of questionable clinical use.
Abstract: B-CLL patients with resistant/relapsed disease or adverse prognostic factors at presentation are suitable for alternative treatments. In the present pilot study we investigated a novel intensive chemo-immunotherapy approach for high-risk, fludarabine pretreated patients. Ten patients with resistant/relapsed, advanced stage B-CLL were included. Age was 37–60 yr (median 53). All but one had an unmutated IgVH status. The treatment schedule included debulking with two DHAP courses followed by alemtuzumab (30 mg, eight doses), followed by peripheral blood progenitor cell (PBPC) mobilization with intermediate/high-dose cyclophosphamide and by autografting after high-dose mitoxantrone+L-Pam. The DHAP-alemtuzumab combination was highly effective. Eight patients out of 10 responded to DHAP, with a single complete remission. Following alemtuzumab. the number of overall responses increased to nine, and the complete remissions to five. After alemtuzumab PB double-positive clonal CD5+/CD19+ lymphocytes dropped, with median purification rate 99.95%. Owing to poor PBPC mobilization, only five patients underwent autografting, and three of these experienced post-graft recurrence. The six patients entering complete remission were free of disease 3–23 mo after study entry, and three of them were still in remission at 3,7, and 22 mo. However, molecular evaluation regularly revealed persistence of minimal residual disease, both in all PBPC collections tested and in post-treatment follow-up samples. The use of DHAP/alemtuzumab appears useful to re-induce disease remission in relapsed/refractory. high-risk B-CLL patients. However, the addition of autograft was not usually feasible and of questionable clinical use. Other strategies should thus be considered for remission maintenance.
TL;DR: Initial results showed that VMPT is an effective salvage therapy with a high proportion of responses and the incidence of neurotoxicities was unexpectedly low.
TL;DR: Cytokine-induced BMC mobilization is feasible in AMI pts and Improvements of myocardial perfusion can be expected after PTCA associated with G- CSF and GM-CSF induced mobilization.
Abstract: AIMS To verify feasibility and safety of bone marrow stem cells (BMC) mobilization in patients (pts) with acute myocardial infarction (AMI) and to monitor the clinical effects of BMC mobilization in terms of myocardial perfusion and function. METHODS AND RESULTS Eight male pts (median age: 50.5 years) treated with a primary PTCA were enrolled. The mobilization regimen consisted of G-CSF 5 microg/kg/12 h from day 0 to day +2 and GM-CSF 2.5 microg/kg/24 h. All pts underwent coronary angiography, intracoronary doppler flow study, echocardiography, and nuclear thallium scan before treatment and at 6 months. All pts showed increased values of WBC and circulating CD34+ following cytokine administration. No patient died. All patients completed a 6-months follow-up: target lesion revascularization rate was 12,5%, target vessel revascularization rate was 37.5%, angiographic mean ejection fraction increased from 49.8+/-11.9 to 55.4+/-8.7 (p=NS), mean coronary flow reserve from 1.63+/-0.42 to 2.5+/-0.4 (p=0.001), mean Thallium uptake raised from 55.56+/-16.42% to 67.56+/-13.66% (p=0.01), and normally perfused segments from 16% to 52% (p=0.01). CONCLUSION Cytokine-induced BMC mobilization is feasible in AMI pts. Improvements of myocardial perfusion can be expected after PTCA associated with G-CSF and GM-CSF induced mobilization. Further studies are required to define the role of BMC-mobilization and the most effective cytokine combination.
TL;DR: The addition of Rituximab to high-dose programs with autograft may improve response and long-term outcome in high-risk B-cell lymphoma patients.
TL;DR: This is an update of the GITMO-IIL trial comparing R-HDS and CHOP-R in high-risk FL 1 47%, and centralized minimal residual disease (MRD) analysis with the bcl-2/IgH was planned on BM cells.
TL;DR: Initial results suggest that MPTD is an effective oral salvage therapy with manageable toxicity and no DVT seen to date in pts with relapsed, refractory MM.
TL;DR: It is concluded that R-HDS is an effective regimen for the induction of complete remissions in pts with newly diagnosed MCL and the manageable toxicity of the program in elderly pts proved that an age-adjusted R- HDS regimen can be safely applied to this age subgroup still producing long-term remissions.
TL;DR: In this paper, patients achieving CR or VGPR following an autologous transplantation-containing regimen were treated with an early consolidation regimen including Bortezomib, Thalidomide and Dexamethsone (VTD).
TL;DR: In this paper, the authors evaluated baseline demographic and clinical parameters to determine their value in predicting outcome of relapsed or refractory patients treated with Thalidomide and Dexamethasone (TD).
01 Jan 2006
TL;DR: A new HLA-DRB5 allele has been identified in an Italian patient during routine HLA typing in order to activate a bone marrow donor search, and the results showed that the HLAs differ for three nucleotide substitutions at codons 57 and 58.
Abstract: A new HLA-DRB5 allele, HLA-DRB5*0113, has been identified in an Italian patient during routine HLA typing in order to activate a bone marrow donor search. HLA typing was performed by different molecular biology techniques, and the results showed that the HLA-DRB5*0113 allele differs from HLA-DRB5*010101 allele for three nucleotide substitutions at codons 57 (GAC-->GAT; Asp) and 58 (GCT-->GAG; Ala-->Glu) of exon 2.
TL;DR: In this paper, the frequency-cumulative incidence-risk factors, of sMDS/AL in a large series of lymphoma patients, treated with the hd-sequential (HDS) chemotherapy approach, followed by peripheral blood progenitor cell (PBPC) autograft.