M A Dimopoulos

National and Kapodistrian University of Athens, Athínai, Attica, Greece

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Publications (341)2063.29 Total impact

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    ABSTRACT: Plasma cell leukemia (PCL) is a rare and aggressive variant of myeloma characterized by the presence of circulating plasma cells. It is classified as either primary PCL occurring at diagnosis or as secondary PCL in patients with relapsed/refractory myeloma. Primary PCL is a distinct clinic-pathological entity with different cytogenetic and molecular findings. The clinical course is aggressive with short remissions and survival duration. The diagnosis is based upon the percentage (20%) and absolute number (2 × 10(9)/l) of plasma cells in the peripheral blood. It is proposed that the thresholds for diagnosis be re-examined and consensus recommendations are made for diagnosis, as well as, response and progression criteria. Induction therapy needs to begin promptly and have high clinical activity leading to rapid disease control in an effort to minimize the risk of early death. Intensive chemotherapy regimens and bortezomib-based regimens are recommended followed by high-dose therapy with autologous stem cell transplantation if feasible. Allogeneic transplantation can be considered in younger patients. Prospective multicenter studies are required to provide revised definitions and better understanding of the pathogenesis of PCL.Leukemia advance online publication, 4 January 2013; doi:10.1038/leu.2012.336.
    Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 11/2012; · 10.16 Impact Factor
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    ABSTRACT: Background:Vascular endothelial growth factor action in tumour angiogenesis is well characterised; nevertheless, it functions as a key element in the promotion of the immune system's evasion by tumours. We sought to investigate the possible direct effect of VEGF on T-cell activation and through which type of VEGF receptor it exerts this effect on cells isolated from ovarian cancer patients' ascites.Methods:T cells isolated from the ascites of ovarian cancer patients were cultured with anti-CD3 and IL-2, with or without VEGF for 14 days and the number of viable T cells was counted. Cytotoxic activity of cultured T cells and expression of VEGF receptor-2 (VEGFR-2), was assayed.Results:The addition of VEGF in cultures significantly reduced the number and proliferation rate of T cells in a dose-dependent manner and CD3(+) T cells expressed VEGFR-2 on their surface upon activation. Experiments with specific anti-VEGFR-2 antibodies revealed that the direct suppressive effect of VEGF on T-cell proliferation is mediated by VEGFR-2. We also showed that VEGF significantly reduced the cytotoxic activity of T cells.Conclusion:Our study showed that ascites-derived T cells secrete VEGF and express VEGFR-2 upon activation. Vascular endothelial growth factor directly suppresses T-cell activation via VEGFR-2.
    British Journal of Cancer 11/2012; 107(11):1869-75. · 5.08 Impact Factor
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    ABSTRACT: The phenotype and function of cells enriched in tumor-propagating activity and their relationship to the phenotypic architecture in multiple myeloma (MM) are controversial. Here, in a cohort of 30 patients we show that MM comprises four hierarchically organised, clonally-related sub-populations which, although phenotypically distinct, share the same oncogenic chromosomal abnormalities as well as immunoglobulin heavy chain complementarity region 3 area sequence. Assessed in xenograft assays, myeloma-propagating activity is the exclusive property of a population characterized by its ability for bi-directional transition between the dominant CD19-CD138+ plasma cell (PC) and a low frequency CD19-CD138- subpopulation (termed Pre-PC); in addition, Pre-PC are more quiescent and unlike PC, are primarily localized at extramedullary sites. As shown by gene expression profiling, compared to PC, Pre-PC are enriched in epigenetic regulators, suggesting that epigenetic plasticity underpins the phenotypic diversification of myeloma-propagating cells. Prospective assessment in paired, pre- and post-treatment bone marrow samples shows that Pre-PC are up to 300-fold more drug-resistant than PC. Thus, clinical drug resistance in MM is linked to reversible, bi-directional phenotypic transition of myeloma-propagating cells. These novel biological insights have important clinical implications in relation to assessment of minimal residual disease and development of alternative therapeutic strategies in MM.
    Blood 11/2012; · 9.78 Impact Factor
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    ABSTRACT: Background The combinations of methotrexate, vinblastine, Adriamycin, cisplatin (Pharmanell, Athens, Greece) (MVAC) or gemcitabine, cisplatin (GC) represent the standard treatment of advanced urothelial cancer (UC). Dose-dense (DD)-MVAC has achieved longer progression-free survival (PFS) than the conventional MVAC. However, the role of GC intensification has not been studied. We conducted a randomized, phase III study comparing a DD-GC regimen with DD-MVAC in advanced UC.Patients and methodsOne hundred and thirty patients were randomly assigned between DD-MVAC: 66 (M 30 mg/m(2), V 3 mg/m(2), A 30 mg/m(2), C 70 mg/m(2) q 2 weeks) and DD-GC 64 (G 2500 mg/m(2), C 70 mg/m(2) q 2 weeks). The median follow-up was 52.1 months (89 events).ResultsThe median overall survival (OS) and PFS were 19 and 8.5 months for DD-MVAC and 18 and 7.8 months for DD-GC (P = 0.98 and 0.36, respectively). Neutropenic infections were less frequent for DD-GC than for DD-MVAC (0% versus 8%). More patients on DD-GC received at least six cycles of treatment (85% versus 63%, P = 0.011) and the discontinuation rate was lower for DD-GC (3% versus 13%).Conclusions Although DD-GC was not superior to DD-MVAC, it was better tolerated. DD-GC could be considered as a reasonable therapeutic option for further study in this patient population.Clinical Trial NumberACTRN12610000845033, www.anzctr.org.au.
    Annals of Oncology 11/2012; · 7.38 Impact Factor
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    ABSTRACT: Asymptomatic multiple myeloma (AMM) is characterized by a constant risk of progression to symptomatic myeloma. To evaluate previously recognized risk factors and to identify high-risk features we analyzed 96 patients with AMM and at least 18 months of follow-up. The progression rate at 1,2, and 3 years was 8%, 15% and 26%, respectively, and the projected 5-year progression rate was 38%. Extensive bone marrow (BM) infiltration, abnormal free light chain (FLC) ratio and serum monoclonal (M)-protein3 gr/dl were the most significant factors for progression, whereas the type of heavy (IgG vs IgA) or light chain or immunoparesis of the uninvolved immunoglobulins were not. Abnormal marrow signal of magnetic resonance imaging of the spine was associated with a significant risk of progression (median 15 months, P=0.001). Extensive BM infiltration 60% (hazard ratio, HR: 13.7, P<0.001) and FLC ratio100 (HR: 9, P=0.003) independently identified a 'very high-risk' group, which included 12.5% of patients with AMM and who progressed 18 months from initial diagnosis. Development of anemia and/or lytic bone lesions were the most common features of symptomatic progression. In conclusion, there is a subgroup of patients who have a substantial risk of progression to symptomatic disease that can be detected at diagnosis (either by extensive BM infiltration60% or FLC ratio100) and may be considered for immediate treatment.Leukemia advance online publication, 27 November 2012; doi:10.1038/leu.2012.309.
    Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 11/2012; · 10.16 Impact Factor
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    ABSTRACT: PURPOSEThis study compared the efficacy and safety of patupilone with those of pegylated liposomal doxorubicin (PLD) in patients with platinum-refractory or -resistant epithelial ovarian, primary fallopian tube, or primary peritoneal cancer. PATIENTS AND METHODS Patients with three or fewer prior regimens were eligible if they had received first-line taxane/platinum-based combination chemotherapy and were platinum refractory or resistant. Patients were randomly assigned to receive patupilone (10 mg/m(2) intravenously every 3 weeks) or PLD (50 mg/m(2) intravenously every 4 weeks).ResultsA total of 829 patients were randomly assigned (patupilone, n = 412; PLD, n = 417). There was no statistically significant difference in overall survival (OS), the primary end point, between the patupilone and PLD arms (P = .195; hazard ratio, 0.93; 95% CI, 0.79 to 1.09), with median OS rates of 13.2 and 12.7 months, respectively. Median progression-free survival was 3.7 months for both arms. The overall response rate (all partial responses) was higher in the patupilone arm than in the PLD arm (15.5% v 7.9%; odds ratio, 2.11; 95% CI, 1.36 to 3.29), although disease control rates were similar (59.5% v 56.3%, respectively). Frequently observed adverse events (AEs) of any grade included diarrhea (85.3%) and peripheral neuropathy (39.3%) in the patupilone arm and mucositis/stomatitis (43%) and hand-foot syndrome (41.8%) in the PLD arm. CONCLUSION Patupilone did not demonstrate significant improvement in OS compared with the active control, PLD. No new or unexpected serious AEs were identified.
    Journal of Clinical Oncology 09/2012; · 18.04 Impact Factor
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    ABSTRACT: The role of thalidomide, bortezomib and lenalidomide in multiple myeloma patients presenting with renal impairment was evaluated in 133 consecutive newly diagnosed patients who were treated with a novel agent-based regimen. A significant improvement of renal function (renalPR (renal partial response)) was observed in 77% of patients treated with bortezomib, in 55% with thalidomide and in 43% with lenalidomide (P=0.011). In multivariate analysis, bortezomib-based therapy was independently associated with a higher probability of renal response compared with thalidomide- or lenalidomide-based therapy. Other important variables included eGFR (estimated glomerular filtration rate) 30 ml/min, age 65 years and myeloma response. Patients treated with bortezomib achieved at least renalPR in a median of 1.34 months vs 2.7 months for thalidomide and >6 months for lenalidomide-treated patients (P=0.028). In multivariate analysis bortezomib-based therapy, higher doses of dexamethasone (160 mg during the first month of treatment), an eGFR 30 ml/min and age 65 years were independently associated with shorter time to renal response. In conclusion, bortezomib-based therapies may be more appropriate for the initial management of patients with myeloma-related renal failure; however, thalidomide and lenalidomide are also associated with significant probability of improvement of their renal function.Leukemia advance online publication, 27 July 2012; doi:10.1038/leu.2012.182.
    Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 07/2012; · 10.16 Impact Factor
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    ABSTRACT: Two pivotal, phase III, randomised, placebo-controlled, registration trials (MM-009 and MM-010) showed that lenalidomide plus dexamethasone was more effective than placebo plus dexamethasone in the treatment of patients with relapsed or refractory multiple myeloma. This pooled, retrospective subanalysis of MM-009 and MM-010 analysed outcomes according to patient age. A total of 704 patients (390 aged <65 years, 232 aged 65-74 years, and 82 aged ≥75 years) received lenalidomide or placebo, both in combination with dexamethasone. The overall response rate (ORR) was significantly higher in patients treated with lenalidomide plus dexamethasone versus placebo plus dexamethasone in all age groups (P < 0.0001 for all). Median progression-free survival (PFS) and median time-to-progression (TTP) were similar, and both were significantly longer with lenalidomide plus dexamethasone in all age groups (P < 0.001 for all). Median overall survival (OS) favoured lenalidomide plus dexamethasone in all age groups, although the difference was not statistically significant. Adverse events of anaemia, febrile neutropenia, deep-vein thrombosis, neuropathy, and gastrointestinal disorders increased with age. Lenalidomide combined with dexamethasone improved the ORR and prolonged PFS, TTP, and OS compared with placebo plus dexamethasone, irrespective of age. This finding was consistent with the overall MM-009 and MM-010 populations.
    International journal of hematology 07/2012; 96(2):254-62. · 1.17 Impact Factor
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    ABSTRACT: Introduction: Natural Killer (NK) cells represent important effectors against hematological and non-hematological malignances. They are highly efficient in killing ex-vivo-derived tumor cells and are effective against tumor cells with stem cell properties, the ultimate target of both conventional and innovative therapies. Clinical evidences however, show that, in vivo, tumors could avoid NK-mediated attack. Indeed it has been shown that NK cell cytolytic activity can be down-regulated by soluble mediators released by tumor cells and/or by immune cell types recruited at the tumor site. The observation that NK cells are often scarce within tumors, despite high local levels of chemokines prompted us to analyze whether tumor cells could avoid NK-mediated immunosurveillance by modulation of NK cell chemokine receptor repertoire. This study has been focused on immunomodulatory role of Neuroblastoma (NB), a poorly differentiated extracranial neuroectodermal tumor that accounts for 15% of all childhood cancer deaths. Material and Methods: NK cells were purified from peripheral blood mononuclear cells of healthy donors by Human NK Cell Isolation kits. NB cell lines utilized: SH-SY-5Y, HTLA-230, SK-NF-1, IMR32, GI-LI-N and SK-N-SH. For cytofluorimetric analysis cells were stained with PE-conjugated mAbs or with unconjugated mAbs followed by conjugated goat anti-mouse second reagent and analyzed by a cytometer. Neuroblastoma-conditioned supernatants were analyzed for the presence of 50 soluble factors using Multiplex Human Cytokine assays. Chemotaxis of neuroblastoma conditioned-NK cells was evaluated by standard assays. Results and Discussion: Freshly purified human NK cells were cultured under trans-well conditions in the presence of NB cell lines. After co-cultures, NK cells were analyzed for the expression of a panel of chemokine receptors known to regulate their migratory capacity. This analysis showed that NB-conditioning up regulates on NK cells CXCR3 and CXCR4 expression. On the contrary NB-conditioned NK cells were characterized by a significative decrease in CX 3 CR1 expression as compared to unconditioned NK cells. Thanks to the analysis of the soluble factors released by the different NB cell lines utilized and by the use of mAb-mediated blocking of specific soluble factors we identified the mediator responsible for the described effect. Interestingly the described immunomodulatory feature was shared only by some of the several NB cell lines utilized.: CD200 is an immunosuppressive molecule which over-expressed in some hematologic malignancies such as B-cell chronic lymphocytic leukemia (B-CLL) and multiple myeloma. It has been also shown to be an independent prognostic factor for patients with acute myeloid leukemia (AML). In this current study, simultaneous CD200 expression and foxp3+ regulatory T cells level were investigated in Iranian patients with AML. Material and Methods: CD200 and its receptor (CD200R) expression levels were examined on bone marrow and peripheral blood leukemic cells obtained from 43 AML patients by Flow cytometry. This technique was also used to determine the frequency of foxp3+ regulatory T cells in these patients. ELISA method was performed to investigate TGF-b and IL-10 production level in serum of patients. Results: Correlation analysis demonstrated simultaneously increasing of foxp3+ regulatory T cells and CD200 expression in AML patients (p = 0.003; r = 0.73). Our clinically poor prognosis patients have shown both higher expression of CD200 and frequency of foxp3+ regulatory T cells (p = 0.01 and p = 0.03, respectively). Moreover, the serum concentration of TGF-b (but not IL-10) was significantly correlated with the expression of CD200 on leukemic cells (p = 0.02). Conclusions: These data signify the CD200 roles in repression and suppression of anti tumor immune system response by stimulation of regulatory mechanisms in AML patients and can suggest that CD200 may have prognostic value in this malignancy.
    EACR, Barcelona, Spain; 07/2012
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    ABSTRACT: The management of multiple myeloma has undergone profound changes over the recent past as a result of advances in our understanding of the disease biology as well as improvements in treatment and supportive care strategies. Notably, recent years have seen a surge in studies incorporating the novel agents thalidomide, bortezomib, and lenalidomide into treatment for different disease stages and across different patient groups. This article presents an update to a previous review of European treatment practices and is based on discussions during an expert meeting that was convened to review novel agent data published or presented at medical meetings until the end of 2011 and to assess their impact on treatment strategies.
    The Oncologist 05/2012; 17(5):592-606. · 4.10 Impact Factor
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    ABSTRACT: Background Activin-A is a transforming growth factor -β superfamily member, which seems to be implicated in the biology of osteolytic disease in multiple myeloma. Design and methods Circulating activin-A was evaluated in 98 newly diagnosed myeloma patients (85 with symptomatic disease), in 40 patients with relapsed myeloma before and after four cycles of lenalidomide and dexamethasone (RD), in 27 healthy controls and in 10 monoclonal gammopathy of undetermined significance patients. Results Patients with newly diagnosed symptomatic myeloma had increased circulating activin-A compared with controls (P < 0.001), while patients with relapsed disease had elevated activin-A even compared with symptomatic patients at diagnosis (P < 0.001). High activin-A correlated with advanced International Staging System stage (P = 0.002), increased bone resorption (P < 0.001) and extensive bone disease (P = 0.03). Low levels of activin-A (<442 pg/ml) were associated with superior median overall survival: not reached versus 59 months (P = 0.04), while activin-A inversely correlated with survival as a continuous variable (P < 0.001). RD did not alter circulating activin-A after four cycles of treatment, even in responders. Conclusions High circulating activin-A correlates with advanced features of myeloma, supporting the rationale for the use of activin-A antagonists, such as sotatercept in myeloma. The inability of RD to reduce activin-A reveals RD as a good candidate for combination therapies with activin-A antagonists in myeloma.
    Annals of Oncology 04/2012; 23(10):2681-6. · 7.38 Impact Factor
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    ABSTRACT: Peripheral neuropathy (PN) is one of the most important complications of multiple myeloma (MM) treatment. PN can be caused by MM itself, either by the effects of the monoclonal protein or in the form of radiculopathy from direct compression, and particularly by certain therapies, including bortezomib, thalidomide, vinca alkaloids and cisplatin. Clinical evaluation has shown that up to 20% of MM patients have PN at diagnosis and as many as 75% may experience treatment-emergent PN during therapy. The incidence, symptoms, reversibility, predisposing factors and etiology of treatment-emergent PN vary among MM therapies, with PN incidence also affected by the dose, schedule and combinations of potentially neurotoxic agents. Effective management of treatment-emergent PN is critical to minimize the incidence and severity of this complication, while maintaining therapeutic efficacy. Herein, the state of knowledge regarding treatment-emergent PN in MM patients and current management practices are outlined, and recommendations regarding optimal strategies for PN management during MM treatment are provided. These strategies include early and regular monitoring with neurological evaluation, with dose modification and treatment discontinuation as indicated. Areas requiring further research include the development of MM-specific, patient-focused assessment tools, pharmacogenomic analysis of patient DNA, and trials to assess the efficacy of pharmacological interventions.
    Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 12/2011; 26(4):595-608. · 10.16 Impact Factor
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    ABSTRACT: Neutropenia is a hematologic adverse event characterized by an absolute neutrophil count (ANC) lower than 1500 cells/mL. This reduction may be due to decreased neutrophil production, accelerated use, a shift in compartments of neutrophils, or a combination of these factors. Neutropenia is often associated with infections, which are major causes of morbidity and mortality in patients with cancer. In patients with multiple myeloma, the novel agents thalidomide, lenalidomide, and bortezomib have improved outcome, but chemotherapy-related neutropenia should be carefully considered. Chemotherapy-related high-risk factors for severe neutropenia include regimens with an expected neutropenia rate of > 50%, such as the 3-drug combinations including lenalidomide plus alkylating agents or doxorubicin, whereas low-risk regimens include combinations of the novel agents with dexamethasone alone. Patient characteristics, disease stage, type of current and previous treatment, and ANC < 1000 cells/mL at baseline are additional factors that define the risk of severe neutropenia. Granulocyte-colony stimulating factor (G-CSF) should be used to manage chemotherapy-related neutropenia so that patients may stay on treatment for a longer time and benefit from it. Primary G-CSF prophylaxis should be used when high-risk regimens are administered or when low/intermediate-risk regimens are used and additional risk factors are present. Reactive G-CSF treatment is indicated when patients undergoing low-risk chemotherapy experience grade 3/4 neutropenia. If ANC restores to > 1000 cells/mL, therapy can be resumed with no dose modifications. In case of persistence of severe neutropenia, treatment should be delayed until ANC reaches > 1000 cells/mL, and dose reductions are necessary.
    Clinical lymphoma, myeloma & leukemia 12/2011; 12(1):5-11.
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    ABSTRACT: In recent years the use of intravenously administered bisphosphonate drugs is widespread, with excellent therapeutic benefits for cancer patients suffering from multiple six months or annually for control and prevention, had fewer caries lesions, better oral hygiene and improved periodontal condition, compared to thosewho rarely visited the dentist due to pain. myeloma, breast, prostate and lung cancer. However, osteonecrosis of the jaws as a side effect of these drugs, which was recently observed, motivated oncologists and dentists internationally to conduct clinical research studies for the prevention, diagnosis and treatment of this lesion. Results of these surveys highlight the importance ofmaintaining good oral health. The absence of epidemiological studies concerning the oral condition of oncology patients and the consequent lack of information of dental problems and the needs of oncology patients receiving intravenous bisphosphonates, was the starting point for the design of this epidemiological research. The purposes of the present studywere: a) to record and evaluate the oral health status of oncology patients, receiving intravenous bisphosphonates, b) to record the cases of those developing osteonecrosis of the jaw, c) to investigate a possible association between oral health status and occurrence of osteonecrosis of the jaw, d) to investigate the possible association of demographic, social and behavioral factors in the emergence and development of osteonecrosis of the jaw. Α nonV interventional clinical trial was conducted, to record the level of oral health of oncology patients receiving intravenous bisphosphonates, by taking three epidemiological indicators and completing a questionnaire. The survey took place in the Oncology Clinic of the University General Hospital "ALEXANDRA" and involved 104 oncology patients, of which 10 had developed osteonecrosis, regardless of gender, age, ethnicity, socioeconomic or educational level, type and stage of cancer. All of the patientswere receiving intravenous zoledronic acid (Zometa) in intravenous infusion, once a month. The main results of the study were: Prevalence and severity of dental caries in patients with bisphosphonate related osteonecrosis of the jaw (BRONJ) were similar to those that have not developed the lesion. Patients with BRONJ, had a similar level of oral hygiene and their periodontal condition was better compared to the level of oral hygiene and the frequency and severity of periodontal diseases in patientswho did not have osteonecrosis. Dental caries and periodontal diseases did not seem to be releasing factors of BRONJ development. Themost serious oral health problems of the patients examined, with or without BRONJ, were caries and periodontal diseases. Regarding dental caries, the index values showed similar levels and variation to that of the general greek population. Age is associated with the development of dental caries: the younger patients showed reduced disease severity compared to older patients. Education level was also associated with dental caries, oral hygiene and periodontal status of the patients: the higher the educational level, the better the oral health. The frequency and the reasoning of visiting the dentist had a direct relationship to dental caries, periodontal status and the level of oral hygiene. Patients who visited the dentist regularly every
    Stomatologia (in Greek). 12/2011; 68(4):187-201.
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    ABSTRACT: Ovarian carcinomas have been classified into types I and II according to the hypothesised mode of carcinogenesis and molecular characteristics. The prognostic significance of this classification has not been studied. Five hundred and sixty-eight patients with histologically confirmed, ovarian, fallopian tube or peritoneal carcinomas, international federation of gynecology and obstetrics (FIGO) stages IIC-IV, treated with paclitaxel/platinum following cytoreductive surgery, were included in this analysis. Type I included low-grade serous, mucinous, endometrioid and clear-cell and type II high-grade serous, unspecified adenocarcinomas and undifferentiated carcinomas. Median overall survival (OS) was 49 months for type I versus 45 for type II (p=0.576). In contrast to type II, there was considerable prognostic heterogeneity among the subtypes included in type I. Cox regression analysis showed that cell-type classification: low-grade serous, mucinous, endometrioid, clear-cell, type II (high-grade serous, unspecified adenocarcinomas, undifferentiated carcinoma) was an independent predictor of survival (respective median OS 121 versus 15 versus 64 versus 29 versus 45 months, p=0.003). On the contrary, histopathological subtype or tumour type (I versus II) did not offer additional prognostic information. The proposed model of ovarian tumourigenesis does not reflect tumour behaviour in advanced disease. Tumour-cell type is the most relevant histopathological prognostic factor in advanced ovarian cancer treated with platinum/paclitaxel.
    European journal of cancer (Oxford, England: 1990) 10/2011; 48(10):1476-83. · 4.12 Impact Factor
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    ABSTRACT: Multiple myeloma, a plasma cell neoplasm, is the second most common hematologic malignancy after non-Hodgkins lymphoma and is responsible for 2% of cancer deaths. Melphalan and prednisone (MP) has been the standard treatment in elderly patients for many decades. The VISTA study evaluated the effect of this combination with or without the first-in-class proteasome inhibitor bortezomib in newly diagnosed myeloma patients who were not candidates for autologous stem cell transplantation. Altogether 682 patients were enrolled and prospectively randomized in this trial. All patients received nine 6-week cycles of oral melphalan (9 mg/m(2)) and prednisone (60 mg/m(2)) on days 1-4, either alone or with bortezomib administered intravenously (1.3 mg/m(2) on days 1, 4, 8, 11, 22, 25, 29 and 32 during the first four cycles and on days 1, 8, 22, 29 during remaining course of therapy). Median time to progression (the primary end point of the trial) was 24 months in the bortezomib-containing group compared with 16.6 months in the control group (p < 0.001). Response was evaluated in 337 patients receiving bortezomib compared with 331 patients in the control group who received MP alone; the percentages of partial response or better was 71 vs 35% (p < 0.001), with complete response seen in 30 vs 4%, respectively (p < 0.001). Median response duration in both groups was 19.9 versus 13.1 months, respectively. Median overall survival has not been reached in VMP group compared with 43 months in the MP group (p < 0.001), and this benefit is maintained after long term follow-up and subsequent antimyeloma therapies. Hematological adverse events (AEs) were similar in both groups, although patients in the bortezomib group experienced more frequent peripheral sensory neuropathy (including 13% grade 3, with less than 1% grade 4). Overall, the occurrence of grade 3 AEs was higher in patients receiving bortezomib (53 vs 44%, p = 0.02), but the risk of grade 4 AEs was identical (28 vs 27%). These results confirm the superiority of MP plus bortezomib combination over MP therapy in treatment-naive patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplantation.
    Immunotherapy 09/2011; 3(9):1033-40. · 2.39 Impact Factor
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    ABSTRACT: Dietary fat, both in terms of quantity and quality, has been implicated to cancer development, either positively or negatively. The aim of this work was to evaluate whether olive oil or monounsaturated fat intake was associated with the development of cancer. A systematic search of relevant studies, published in English, between 1990 and March 1, 2011, was performed through a computer-assisted literature tool (i.e., Pubmed). In total 38 studies were initially allocated; of them 19 case-control studies were finally studied (13800 cancer patients and 23340 controls were included). Random effects meta-analysis was applied in order to evaluate the research hypothesis. It was found that compared with the lowest, the highest category of olive oil consumption was associated with lower odds of having any type of cancer (log odds ratio = -0.41, 95%CI -0.53, -0.29, Cohran's Q = 47.52, p = 0.0002, I-sq = 62%); the latter was irrespective of the country of origin (Mediterranean or non-Mediterranean). Moreover, olive oil consumption was associated with lower odds of developing breast cancer (logOR = -0,45 95%CI -0.78 to -0.12), and a cancer of the digestive system (logOR = -0,36 95%CI -0.50 to -0.21), compared with the lowest intake. The strength and consistency of the findings states a hypothesis about the protective role of olive oil intake on cancer risk. However, it is still unclear whether olive oil's monounsaturated fatty acid content or its antioxidant components are responsible for its beneficial effects.
    Lipids in Health and Disease 07/2011; 10:127. · 2.31 Impact Factor
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    ABSTRACT: Promising new drugs are being evaluated for treatment of multiple myeloma (MM), but their impact should be measured against the expected outcome in patients failing current therapies. However, the natural history of relapsed disease in the current era remains unclear. We studied 286 patients with relapsed MM, who were refractory to bortezomib and were relapsed following, refractory to or ineligible to receive, an IMiD (immunomodulatory drug), had measurable disease, and ECOG PS of 0, 1 or 2. The date patients satisfied the entry criteria was defined as time zero (T0). The median age at diagnosis was 58 years, and time from diagnosis to T0 was 3.3 years. Following T0, 213 (74%) patients had a treatment recorded with one or more regimens (median=1; range 0–8). The first regimen contained bortezomib in 55 (26%) patients and an IMiD in 70 (33%). A minor response or better was seen to at least one therapy after T0 in 94 patients (44%) including partial response in 69 (32%). The median overall survival and event-free survival from T0 were 9 and 5 months, respectively. This study confirms the poor outcome, once patients become refractory to current treatments. The results provide context for interpreting ongoing trials of new drugs.Keywords: multiple myeloma; relapse; natural history; survival
    Leukemia 07/2011; 26(1):149-157. · 10.16 Impact Factor
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    ABSTRACT: Early-stage epithelial ovarian cancer represents a prognostically heterogenous group. We studied prognostic factors in patients treated with adjuvant paclitaxel/carboplatin chemotherapy. Data was extracted from 147 patients with FIGO stage IA/IB, grade 2/3 or stage IC/IIA (any grade) who underwent primary surgery followed by paclitaxel/carboplatin chemotherapy. Median follow-up was 88 months. Ten-year relapse-free (RFS) and disease-specific survival (DSS) were: 81% (95% confidence interval [CI]: 73-89) and 81% (95% CI: 73-89). On multivariate analysis, non serous histology was associated with reduced risk for RFS (0.294, 95% CI: 0.112-0.577, p=0.001) and DSS (0.194, 95% CI: 0.075-0.504, p=0.001), while high-risk category (stage IC/IIA and grade 2/3) with increased risk for RFS (3.989, 95% CI: 1.189-13.389, p=0.009) and DSS (3.989, 95% CI: 1.064-16.386, p=0.038). The combination of histology and grade identified 3 groups with distinctly different 10-year RFS and DSS rates (p<0.001): grade 1 (100% and 100%), non-serous grade 2/3 (83% and 86%) and serous grade 2/3 (60% and 60%). Serous histology is an adverse prognostic factor in early-stage ovarian cancer treated with adjuvant paclitaxel/carboplatin. Risk stratification according to histology and grade is a useful discriminator of prognosis and can be used in the design of future studies.
    Gynecologic Oncology 07/2011; 123(1):37-42. · 3.93 Impact Factor
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    M A Dimopoulos, M Hussein, A S Swern, D Weber
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    ABSTRACT: This analysis assessed the effect of lenalidomide on progression-free survival (PFS). Patients with relapsed or refractory multiple myeloma (RRMM) who received lenalidomide plus dexamethasone in the MM-009 and MM-010 trials were pooled and those who had not progressed and were still receiving lenalidomide at 12 months were included. The median follow-up of surviving patients was 48 months. Of 353 patients who received lenalidomide plus dexamethasone, 116 (33%) had not progressed. Overall, 52 patients (45%) had no dose reductions, 25 (22%) had dose reductions ≥12 months and 39 (34%) had dose reductions before 12 months. Patients who had dose reductions ≥12 months had a significantly longer median PFS than those who had reductions before 12 months (P=0.007) or no dose reductions (P=0.039) (not reached vs 28.0 vs 36.8 months, respectively). In a multivariate Cox regression model, dose reduction ≥12 months was an independent predictor of improved PFS (hazard ratio, 0.47; 95% confidence interval, 0.23-0.98) after adjusting for patient characteristics. The data suggest that to achieve maximum PFS benefit, patients with RRMM should be treated for ≥12 months with full-dose lenalidomide plus dexamethasone. Thereafter, patients may benefit from lower-dose continued therapy; prospective studies are needed to confirm these findings.
    Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 07/2011; 25(10):1620-6. · 10.16 Impact Factor

Publication Stats

9k Citations
2,063.29 Total Impact Points


  • 1999–2014
    • National and Kapodistrian University of Athens
      • • Division of Clinical Therapeutics
      • • Faculty of Medicine
      Athínai, Attica, Greece
  • 2013
    • Clínica Universidad de Navarra
      Madrid, Madrid, Spain
  • 2011–2012
    • Wiener Krankenanstaltenverbund
      Wien, Vienna, Austria
    • University Medical Center Utrecht
      • Department of Hematology
      Utrecht, Provincie Utrecht, Netherlands
  • 1998–2012
    • Alexandra Regional General Hospital
      Athínai, Attica, Greece
  • 1999–2011
    • Athens State University
      Athens, Alabama, United States
  • 2002–2010
    • Κωνσταντοπούλειο νοσοκομείο Νέας Ιωνίας (Η Αγία Όλγα)
      Athínai, Attica, Greece
    • University of Ioannina
      Yannina, Epirus, Greece
  • 2009
    • Άγιος Σάββας Αντικαρκινικό Νοσοκομείο
      Athínai, Attica, Greece
  • 2005–2009
    • Attikon University Hospital
      • Department of Internal Medicine IV
      Athens, Attiki, Greece
    • University of Patras
      • School of Medicine
      Patrís, Kentriki Makedonia, Greece
    • BMI The Alexandra Hospital
      Cheadle Hulme, England, United Kingdom
  • 1991–2009
    • University of Texas MD Anderson Cancer Center
      • Department of Stem Cell Transplantation & Cellular Therapy
      Houston, TX, United States
  • 2008
    • Mayo Foundation for Medical Education and Research
      • Division of Hematology
      Rochester, Michigan, United States
  • 2007–2008
    • Yale-New Haven Hospital
      • Department of Pathology
      New Haven, Connecticut, United States
    • Yale University
      • School of Medicine
      New Haven, CT, United States
  • 2000–2008
    • Hygeia Hospital
      Athínai, Attica, Greece
    • University Hospital of Ioannina
      Yannina, Epirus, Greece
      Athínai, Attica, Greece
  • 2001–2004
    • Aristotle University of Thessaloniki
      • Laboratory of Ecology
      Saloníki, Central Macedonia, Greece
    • Θεαγένειο Αντικαρκινικό Νοσοκομείο
      Saloníki, Central Macedonia, Greece
  • 2000–2004
    • Evangelismos Hospital
      Athínai, Attica, Greece
  • 2003
    • Hippokration General Hospital, Athens
      Athínai, Attica, Greece
  • 2000–2003
    • Hellenic Cooperative Oncology Group
      Athínai, Attica, Greece
  • 1999–2000
    • University of Crete
      • Department of Medical Oncology
      Réthymnon, Kriti, Greece
  • 1994
    • Royal Melbourne Hospital
      Melbourne, Victoria, Australia
  • 1989–1994
    • Laiko Hospital
      Athínai, Attica, Greece
  • 1990
    • General Hospital of Komotini "Sismanoglio"
      Komotina, East Macedonia and Thrace, Greece