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Alessandro Corso

Publications and source records attributed to Alessandro Corso.

13 recordsLinked to original sources
PubMed2006

Changes in multiple myeloma epidemiology in the last thirty years: a single centre experience.

In this study we have evaluated 772 multiple myeloma (MM) patients for clinical presentation, response to treatment, relapse modality, and survival in the last 30 years. Patients were divided, according to the date of diagnosis in group I or group II (before and after 1994, respectively) and therapy (high or conventional dose). Bone pain and early deaths were statistically reduced in group II, whereas MM that evolved from monoclonal gammopathy of undetermined significance (MGUS) had increased. The efficacy of high dose therapy (HDT) over conventional dose therapy (CDT) was confirmed through analysis of response rate, progression free, and overall survival. Relapse modality was similar after HDT or CDT. Among older patients, those diagnosed after 1994 lived longer than those diagnosed before 1994. In the last 30 years, the clinical presentation of multiple myeloma remained substantially unchanged. The new therapeutic approaches, chemotherapy and supportive therapy, allowed better control of the disease with an improvement of survival.

Adult↗
PubMed2005

Zoledronic acid down-regulates adhesion molecules of bone marrow stromal cells in multiple myeloma: a possible mechanism for its antitumor effect.

BACKGROUND: Myeloma plasma cells interact with the bone marrow microenvironment which, in turn, supports their growth and protects them from apoptosis. In vitro studies have demonstrated the antitumor potential of zoledronic acid (ZOL) on myeloma cell lines, but few data are available on its effects on bone marrow stromal cells (BMSCs). The aim of the current study was to evaluate the antiproliferative and apoptotic effect of ZOL on BMSCs, as well as its effect on the expression of adhesion molecules. METHODS: BMSCs, obtained from bone marrow mononucleated cells of 8 patients with multiple myeloma, were treated with increasing concentrations of ZOL for 3 days. Cytotoxic effect was analyzed by 3-(4-5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide; thiazolyl blue (MTT) assay whereas the induction of apoptosis was evaluated by flow cytometric detection of fluorescein isothiocyanate-labeled annexin V, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay, and nuclear changes. Moreover, expression of CD106, CD56, CD50, CD49d, CD44, and CD40 was analyzed by flow cytometry. Data were evaluated by the Friedman test. RESULTS: After 3 days of exposure at concentrations of 10(-4) to 10(-5) M, ZOL induced a decrease in proliferation (P < 0.0001) and an increase in apoptosis (P < 0.002). Analysis of culture supernatants showed that myeloma BMSCs expressed interleukin (IL)-6, negligible levels of tumor necrosis factor-alpha, and no IL-1beta. In vitro exposure to the lowest concentrations of ZOL decreased IL-6 production by BMSCs. Among the adhesion molecules, CD106, CD54, CD49d, and CD40, which were strongly expressed at baseline, showed a statistically significant reduction compared with controls after exposure to ZOL. CONCLUSIONS: ZOL interfered with myeloma BMSCs by reducing proliferation, increasing apoptosis, and modifying the pattern of expression of adhesion molecules, especially those involved in plasma cell binding. These effects on BMSCs might explain the antitumor activity of ZOL.

Apoptosis↗
PubMed2005

Bone marrow CD34+ cell count is predictive for adequate peripheral progenitor cell collection.

Several studies have investigated the influence of clinical and biological variables on mobilisation of peripheral blood progenitor cells (PBPCs). The aim of this study was to evaluate the role of steady-state bone marrow (BM) CD34+ cells as a predictive parameter of PBPC yield. We studied 90 patients with multiple myeloma (MM) (41 patients), non-Hodgkin's lymphoma (NHL) (25 patients) or acute myeloid leukaemia (AML) (24 patients), mobilised with chemotherapy and growth factor. The median time from first treatment to mobilisation was 5 months. Only one patient was previously exposed to alkylating agents. The median BM CD34+ count at mobilisation was 833 microl(-1) (range: 1.4-15.540) corresponding to 1.51% of mononuclear cells (range: 0.02-8.6). Sixty-six patients (73%) reached the optimal target of 4 x 10(6) kg(-1) CD34+ cells with 1 (18 patients), 2 (42 patients) or 3 leukaphereses (6 patients). Eleven patients (12%) mobilised less than 4 x 10(6) kg(-1) CD34+ cells and 13 (15%) failed mobilisation. Among the laboratory and clinical parameters evaluated at the time of mobilisation, only BM CD34+ count was a predictive factor for adequate collection (P = 0.04), particularly in MM patients (P = 0.003). In this setting, a BM concentration of CD34+ cells lower than 66 microL(-1) was associated with a higher probability of inadequate collection.

Adult↗
PubMed2005

Zoledronic acid exerts its antitumor effect in multiple myeloma interfering with the bone marrow microenvironment.

Multiple myeloma (MM) is a B-cell malignancy characterized by an excess of monotypic plasma cells which localize almost exclusively in the bone marrow provoking bone destruction via the activation of the osteoclasts. The bone marrow microenvironment, mainly through stromal cells, is strictly involved in the evolution of the disease supporting MM cell growth and survival [1]. MM plasma cells reside in the bone marrow by binding to adhesion molecule of extracellular matrix (ECM) and stromal cells. The activation of some signaling pathways within the stromal cells increases the production of several cytokines which in turn favors the myeloma cell proliferation and survival [2-6], and enhance the drug resistance by anti-apoptotic mechanisms [1,7-9]. Novel therapeutic agents target not only the myeloma cells but also the interaction between MM cells and the bone marrow microenvironment [8]. Bisphosphonates (Bps) interfere as well with bone microenvironment inhibiting the survival of stromal cells and hampering the contact between plasma and stromal cells. In this review we will revise preclinical evidences, and the potential mechanisms of the antitumor activity of zoledronic acid.

Animals↗
PubMed2004

The VAD-DCEP sequence is an effective pre-transplant therapy in untreated multiple myeloma.

BACKGROUND AND OBJECTIVES: Standard treatment for patients with multiple myeloma is debulking chemotherapy with non-alkylating agents followed by a regimen to mobilize peripheral blood stem cells (PBSC) and the transplantation of the mobilized, autologous PBSC. The aim of this study was to evaluate the efficacy of a new regimen and compare it with that of a previous regimen. DESIGN AND METHODS: In a large cohort of 106 patients (group I) we administered a new pre-transplant program which includes 2 courses of pulsed-VAD (vincristine, adriamycin, dexamethasone) followed by 2 courses of DCEP (dexamethasone, cyclophosphamide, etoposide and cis-platinum). We compared the efficacy of this new VAD-DCEP sequence, in terms of mobilizing capacity, toxicity and anti-myeloma activity in comparison with that of the previous VAD-high-dose cyclophosphamide program (group II, 40 patients). RESULTS: In group I 81/106 (76.4%) patients yielded >or= 4x10(6)/kg CD34+ cells, as did 30/40 (75%) in group II but with a significantly higher toxicity in this latter group. In detail, 9 patients in group I (8.5%) had WHO grade III neutropenia versus 35 in group II (87.5%), 5 patients of group I (4.7%) had grade III thrombocytopenia versus 12 patients in group II (30%), and 8 patients in group I (7.5%) experienced an infections fever versus 9 patients in group II (22.5%). Therefore, nearly all patients in group II had to be admitted to hospital (39/40, 97.5%). There was a higher percentage of responses (CR+VGPR+PR) in group I than in group II: 73% versus 50% (p=0.02). INTERPRETATION AND CONCLUSIONS: the VAD-DCEP sequence has an adequate mobilizing capacity, without significant toxicity, and a good anti-myeloma activity, and therefore represents a safe and effective therapeutic approach for multiple myeloma patients at the onset of their disease.

Adult↗
PubMed2002

Pipobroman is safe and effective treatment for patients with essential thrombocythaemia at high risk of thrombosis.

Essential thrombocythaemia (ET) is a disease associated with an elevated risk of thrombosis. This study evaluated the efficacy and safety of pipobroman (PB) in the long-term control of ET patients who had, at diagnosis, one or more of the following currently known risk factors for thrombosis or haemorrhage (high-risk patients): age > 60 years, history of thrombosis or haemorrhage, platelets >1000 x 10(9)/l. From 1978 to 2000, with a median follow-up of 10 years, 118 previously untreated high-risk ET patients (median age 62 years, range 25-82), were treated with PB at the starting dose of 0.8-1 mg/kg/d. All patients reached a platelet count <600 x 10(9)/l and 91% achieved a platelet count <400 x 10(9)/l. During follow-up, 13 patients had thrombosis, with a 10-year cumulative risk of 14%. Acute myeloid leukaemia, myelofibrosis and solid tumours occurred in three, two and seven patients with a 10-year cumulative risk of 3%, 2% and 7% respectively. Actuarial survival at 20 years was 64% and the standardized mortality ratio was 1.1 (95% CI: 0.7-1.7), not statistically different from the general population (P = 0.54). Age was associated with a higher risk of death (P = 0.00009) and thrombosis (P = 0.003). The duration of PB treatment did not correlate with the occurrence of second malignancies. This study, with a median follow-up of 10 years, demonstrates that pipobroman is effective and well tolerated. The low cumulative 10-year risk of thrombosis, leukaemia and solid tumours indicates that pipobroman is an adequate treatment for patients with high risk ET.

Adult↗
PubMed2002

Advantages of using thalidomide for the management of refractory myeloma patients.

A group of 11 heavily pretreated patients receiving low-dose thalidomide was compared with a similar group of 10 patients with refractory myeloma treated with a convention-al oral chemotherapy. This study shows that thalidomide is not only effective in controlling the neoplastic clone but more-over, thanks to its low toxicity, allows out-patient management of these subjects.

Aged↗
PubMed2002

A combination of dexamethasone, cyclophosphamide, etoposide, and cisplatin is less toxic and more effective than high-dose cyclophosphamide for peripheral stem cell mobilization in multiple myeloma.

BACKGROUND AND OBJECTIVES: The purpose of this study was to compare the efficacy and toxicity of two regimens for peripheral blood stem cell (PBSC) mobilization in multiple myeloma (MM) patients. DESIGN AND METHODS: From 1995 to 2001, 116 patients were enrolled in two high-dose programs including autologous transplantation, adopting two mobilizing regimens: 61 patients were mobilized with high-dose cyclophosphamide (HD-Cy) at 4 g/m2 (group I), and 55 patients with DCEP (dexamethasone, cyclophosphamide, etoposide, and cisplatin) (group II), both followed by granulocyte colony-stimulating factor (G-CSF 5 mg/Kg/day) started 48 hours after chemotherapy. RESULTS: The median number of CD34+ cells harvested was similar in the two groups (5.9 vs 5.82x106 cells/kg). The target of at least 4x106 cells/kg was reached in a higher percentage of patients in the DCEP group (75 vs 59%) (p=0.05). The proportion of poor mobilizers (<2x106 CD34+ cells/kg) was 21% with HD-Cy and 13% with DCEP (P=NS). In group I, 10 patients (16%) required packed red cell transfusions, 5 patients (8%) platelet support, and the majority of patients (87%) had a neutrophil count below 500/mL, whereas none did so in group II (p=0.0009, p=0.01, p=0.0009, respectively). Neutropenia-related fever occurred in 18% of patients in group I versus 0% in group II (p=0.0005). WHO grade >II extra-hematologic toxicities (microhematuria, cystitis, infections) were seen in 8 patients (13%) of group I vs 0 in group II (p=0.007). INTERPRETATION AND CONCLUSIONS: DCEP is a better tolerated and more effective regimen than HD-Cy for peripheral stem cell mobilization in MM patients assigned to high-dose therapy programs.

Adult↗