113 results found
Kumar SK, Dimopoulos MA, Kastritis E, et al., 2017, Natural history of relapsed myeloma, refractory to immunomodulatory drugs and proteasome inhibitors: a multicenter IMWG study., Leukemia, Vol: 31, Pages: 2443-2448
Introduction of new myeloma therapies offers new options for patients refractory to immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs). In this multicenter study, patients with relapsed multiple myeloma, who have received at least three prior lines of therapy, are refractory to both an IMiD (lenalidomide or pomalidomide) and a PI (bortezomib or carfilzomib), and have been exposed to an alkylating agent were identified. The time patients met the above criteria was defined as time zero (T0). Five hundred and forty-three patients diagnosed between 2006 and 2014 were enrolled in this study. Median age at T0 was 62 years (range 31-87); 61% were males. The median duration between diagnosis and T0 was 3.1 years. The median number of lines of therapy before T0 was 4 (range 3-13). The median overall survival (OS) from T0 for the entire cohort was 13 (95% confidence interval (CI) 11, 15) months. At least one regimen recorded after T0 in 462 (85%) patients, with a median (95% CI) progression-free survival and OS from T0 of 5 (4, 6), and 15.2 (13, 17) months, respectively. The study provides the expected outcome of relapsed multiple myeloma that is refractory to a PI and an IMiD, a benchmark for comparison of new therapies being evaluated.
Kostopoulos IV, Paterakis G, Pavlidis D, et al., 2017, Clonal evolution is a prognostic factor for the clinical progression of monoclonal B-cell lymphocytosis, BLOOD CANCER JOURNAL, Vol: 7, ISSN: 2044-5385
Rifkin RM, Davies FE, Palumbo A, et al., 2016, Global, Prospective, Non-Interventional, Observational Study of Presentation, Treatment Patterns, and Outcomes in Multiple Myeloma Patients: The Insight-MM Study, 58th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH), Publisher: AMER SOC HEMATOLOGY, ISSN: 0006-4971
Spanoudakis E, Papoutselis M, Terpos E, et al., 2016, Overexpression of RANKL by invariant NKT cells enriched in the bone marrow of patients with multiple myeloma, BLOOD CANCER JOURNAL, Vol: 6, ISSN: 2044-5385
Engert A, Balduini C, Brand A, et al., 2016, The European Hematology Association Roadmap for European Hematology Research: a consensus document., Haematologica, Vol: 101, Pages: 115-208, ISSN: 0390-6078
The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at €23 billion per year, a level of cost that is not matched in current European hematology research funding. In recent decades, hematology research has improved our fundamental understanding of the biology of blood disorders, and has improved diagnostics and treatments, sometimes in revolutionary ways. This progress highlights the potential of focused basic research programs such as this EHA Roadmap.The EHA Roadmap identifies nine 'sections' in hematology: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation. These sections span 60 smaller groups of diseases or disorders.The EHA Roadmap identifies priorities and needs across the field of hematology, including those to develop targeted therapies based on genomic profiling and chemical biology, to eradicate minimal residual malignant disease, and to develop cellular immunotherapies, combination treatments, gene therapies, hematopoietic stem cell treatments, and treatments that are better tolerated by elderly patients.
Rahemtulla A, Terpos E, 2015, Hodgkin's lymphoma (relapsed or refractory): autologous stem cell therapy., BMJ Clin Evid, Vol: 2015
INTRODUCTION: People with Hodgkin's lymphoma usually present with a lump in the neck or upper chest, but a quarter of people also have fever, sweating, weight loss, fatigue, and itch. Almost all people with localised disease can be cured and, even among people with relapsed advanced disease, almost 50% to 60% survive event-free for 4 years or more. However, a proportion of patients with early Hodgkin's lymphoma with poor prognostic factors (up to 15%) or with advanced disease (40%-50%) still relapses or has refractory disease. METHODS AND OUTCOMES: We conducted a systematic overview, aiming to answer the following clinical question: What are the effects of high-dose chemotherapy plus autologous stem cell therapy for relapsed or refractory Hodgkin's lymphoma? We searched: Medline, Embase, The Cochrane Library, and other important databases up to September 2014 (Clinical Evidence overviews are updated periodically; please check our website for the most up-to-date version of this overview). RESULTS: Searching of electronic databases retrieved 298 studies. Appraisal of titles and abstracts led to the exclusion of 245 studies and the further review of 53 full publications. Of the 53 full articles evaluated, one systematic review was added. We performed a GRADE evaluation for three PICO combinations. CONCLUSIONS: In this systematic overview, we categorised the efficacy for one intervention, based on information relating to the effectiveness and safety of high-dose chemotherapy plus autologous stem cell therapy (versus conventional chemotherapy).
Psaltopoulou T, Sergentanis TN, Sergentanis IN, et al., 2015, Alcohol intake, alcoholic beverage type and multiple myeloma risk: a meta-analysis of 26 observational studies, LEUKEMIA & LYMPHOMA, Vol: 56, Pages: 1484-1501, ISSN: 1042-8194
Makarona K, Caputo VS, Costa JR, et al., 2014, Transcriptional and epigenetic basis for restoration of G6PD enzymatic activity in human G6PD-deficient cells, BLOOD, Vol: 124, Pages: 134-141, ISSN: 0006-4971
Diamantopoulos PT, Polonyfi K, Sofotasiou M, et al., 2014, Survivin messenger RNA levels in Epstein-Barr virus-positive patients with leukemic low-grade B-cell lymphomas expressing the latent membrane protein 1: evidence of apoptotic function?, Clin Lymphoma Myeloma Leuk, Vol: 14, Pages: 56-60
BACKGROUND: Epstein-Barr virus (EBV) is a ubiquitous pathogen that chronically infects B lymphocytes and is implicated in the pathogenesis of lymphoproliferative diseases. Latent membrane protein 1 (LMP1), the major oncoprotein of the virus, has been shown to inhibit apoptosis and trigger survivin expression in malignant cell lines. LMP1 expression has been detected in patients with chronic lymphocytic leukemia, but its properties have not been studied in patients with low-grade B-cell lymphomas. Recent data show that LMP1 can simultaneously induce and inhibit apoptosis in B cells. We detected LMP1 messenger RNA (mRNA) in patients with leukemic low-grade B-cell lymphoma and correlated the expression of the antiapoptotic molecule survivin to that of LMP1 in this group of patients. PATIENTS AND METHODS: Peripheral whole blood from 64 patients with low-grade B-cell lymphoma was tested by quantitative reverse transcriptase-polymerase chain reaction (PCR) for the presence of the BXLF-1 gene of EBV, and positive samples were tested by conventional PCR for LMP1 expression. Accordingly, survivin mRNA levels were measured by quantitative reverse transcriptase PCR in all samples and compared between LMP1-positive (LMP1(+)) and LMP1(-) patients. RESULTS: The BXLF-1 gene was detected in 27 of 64 patients (42%). LMP1 was expressed in 22 of 27 (81%) EBV(+) patients. Survivin expression was found to be 6.36 times higher in LMP1(-) patients than in LMP1(+) patients (P = .008). CONCLUSION: Our results imply that in patients with non-EBV-related leukemic low-grade B-cell lymphoma, LMP1 expression is possibly correlated to apoptosis, as indicated by the lower survivin mRNA levels in LMP1(+) patients.
Katodritou E, Vadikolia C, Lalagianni C, et al., 2014, "Real-world" data on the efficacy and safety of lenalidomide and dexamethasone in patients with relapsed/refractory multiple myeloma who were treated according to the standard clinical practice: a study of the Greek Myeloma Study Group., Ann Hematol, Vol: 93, Pages: 129-139
Lenalidomide and dexamethasone (RD) is a standard of care for relapsed/refractory multiple myeloma (RRMM), but there is limited published data on its efficacy and safety in the "real world" (RW), according to the International Society of Pharmacoeconomics and Outcomes Research definition. We studied 212 RRMM patients who received RD in RW. Objective response (≥PR (partial response)) rate was 77.4 % (complete response (CR), 20.2 %). Median time to first and best response was 2 and 5 months, respectively. Median time to CR when RD was given as 2nd or >2(nd)-line treatment at 4 and 11 months, respectively. Quality of response was independent of previous lines of therapies or previous exposure to thalidomide or bortezomib. Median duration of response was 34.4 months, and it was higher in patients who received RD until progression (not reached versus 19 months, p < 0.001). Improvement of humoral immunity occurred in 60 % of responders (p < 0.001) and in the majority of patients who achieved stable disease. Adverse events were reported in 68.9 % of patients (myelosuppression in 49.4 %) and 12.7 % of patients needed hospitalization. Peripheral neuropathy was observed only in 2.5 % of patients and deep vein thrombosis in 5.7 %. Dose reductions were needed in 31 % of patients and permanent discontinuation in 38.9 %. Median time to treatment discontinuation was 16.8 months. Performance status (PS) and initial lenalidomide dose predicted for treatment discontinuation. Extra-medullary relapses occurred in 3.8 % of patients. Our study confirms that RD is effective and safe in RRMM in the RW; it produces durable responses especially in patients who continue on treatment till progression and improves humoral immunity even in patients with stable disease.
Dimopoulos MA, Delimpasi S, Katodritou E, et al., 2014, Significant improvement in the survival of patients with multiple myeloma presenting with severe renal impairment after the introduction of novel agents., Ann Oncol, Vol: 25, Pages: 195-200
BACKGROUND: Renal impairment (RI) is a common presenting complication of multiple myeloma (MM); the availability of new treatments has improved the outcomes of patients with MM; however, their impact on the survival of patients who present with RI has not been extensively studied. PATIENTS AND METHODS: We analyzed the characteristics and outcomes of 1773 consecutive unselected patients who were treated for symptomatic myeloma since January 1990. RESULTS: Although there was a significant increase in the proportion of patients of advanced age in the more recent periods, the frequency of RI as well as the proportion of patients who presented with severe RI (eGFR < 30 ml/min/1.73 m(2)) remained unchanged around 18%. Thus, after adjustment for age, there was a decrease in the risk of severe RI at presentation after 2000. Myeloma response rates (≥PR) to frontline therapy have substantially increased, and this was translated in a significant increase in the median survival. Specifically for patients with severe RI, the median OS has improved from 18 and 19.5 months in the 1990-1994 and 1995-1999 to 29 and 32 months for the periods 2000-2004 and after 2005 (P = 0.005). Severe RI was associated with a high risk of early death (12% versus 7% for patients with moderate RI versus 3% for patients with mild or no RI (P < 0.001), especially among older patients, and has remained unchanged over time. CONCLUSIONS: There has been a major improvement in the survival of patients with severe RI in the past decade, despite the increasing numbers of patients of advanced age. However, the risk of early death remains high in patients with severe RI, especially in the elderly.
Terpos E, Apperley J, Milojkovic D, 2013, Imatinib and chronic myeloid leukemia: close to the bone, LEUKEMIA & LYMPHOMA, Vol: 54, Pages: 1581-1582, ISSN: 1042-8194
Chaidos A, Barnes CP, Cowan G, et al., 2013, Clinical drug resistance linked to interconvertible phenotypic and functional states of tumor-propagating cells in multiple myeloma, BLOOD, Vol: 121, Pages: 318-328, ISSN: 0006-4971
Chaidos A, Barnes CP, Cowan G, et al., 2012, Clinical Drug Resistance Linked to Inter-Convertible Phenotypic and Functional States of Tumor-Propagating Cells in Multiple Myeloma, 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH), Publisher: AMER SOC HEMATOLOGY, ISSN: 0006-4971
Gkotzamanidou M, Dimopoulos MA, Kastritis E, et al., 2012, Sclerostin: a possible target for the management of cancer-induced bone disease., Expert Opin Ther Targets, Vol: 16, Pages: 761-769
INTRODUCTION: Sclerostin is a cysteine-knot-containing protein, which is produced by osteocytes and inhibits osteoblast function. The aim of this review is to summarize the data about the role of sclerostin in cancer-induced bone disease. AREAS COVERED: We performed a thorough search for articles in the PubMed using the words "sclerostin, cancer, multiple myeloma", and for similar abstracts that were presented in the ASH and ASCO annual meetings (2005 - 2011). In multiple myeloma, sclerostin is produced by myeloma cells and elevated in the serum or the plasma of the patients, and correlates with extensive bone disease and adverse myeloma features. In prostate cancer, sclerostin expression is reduced and in combination with bone morhogenetic protein-6 and noggin expression may serve as prognostic predictor for metastatic progression. In breast cancer, in vitro data suggest that the malignant cell induces the expression of sclerostin to inhibit osteoblasts in the metastatic bone area. EXPERT OPINION: Sclerostin may play a role in inhibiting bone formation in the biology of bone metastases in breast cancer and of myeloma-related bone disease. The results of phase I/II studies with anti-sclerostin drugs in subjects with low bone mass may lead to the potential clinical investigation of these agents in cancer-induced bone disease.
Salooja N, Patel B, Todd J, et al., 2012, Dikkopf-1 is elevated in very long-term survivors of haematopoietic stem cell transplantation, 38th Annual Meeting of the European-Group-for-Blood-and-Marrow-Transplantation (EBMT), Publisher: NATURE PUBLISHING GROUP, Pages: S338-S338, ISSN: 0268-3369
Dimopoulos MA, Kastritis E, Michalis E, et al., 2012, The International Scoring System (ISS) for multiple myeloma remains a robust prognostic tool independently of patients' renal function., Ann Oncol, Vol: 23, Pages: 722-729
BACKGROUND: The International Staging System (ISS) is the most widely used staging system for patients with multiple myeloma (MM). However, serum β2-microglobulin increases in renal impairment (RI) and there have been concerns that ISS-3 stage may include 'up-staged' MM patients in whom elevated β2-microglobulin reflects the degree of renal dysfunction rather than tumor load. PATIENTS AND METHODS: In order to assess the impact of RI on the prognostic value of ISS, we analyzed 1516 patients with symptomatic MM and the degree of RI was classified according to the Kidney Disease Outcomes Quality Initiative-Chronic Kidney Disease (CKD) criteria. RESULTS: Forty-eight percent patients had stages 3-5 CKD while 29% of patients had ISS-1, 38% had ISS-2 and 33% ISS-3. The frequency and severity of RI were more common in ISS-3 patients. RI was associated with inferior survival in univariate but not in multivariate analysis. When analyzed separately, ISS-1 and ISS-2 patients with RI had inferior survival in univariate but not in multivariate analysis. In ISS-3 MM patients, RI had no prognostic impact either in univariate or multivariate analysis. Results were similar, when we analyzed only patients with Bence-Jones >200 mg/day. CONCLUSIONS: ISS remains unaffected by the degree of RI, even in patients with ISS-3, which includes most patients with renal dysfunction.
Kastritis E, Kyrtsonis M-C, Hatjiharissi E, et al., 2011, No significant improvement in the outcome of patients with Waldenström's macroglobulinemia treated over the last 25 years., Am J Hematol, Vol: 86, Pages: 479-483
The treatment of Waldenström's macroglobulinemia (WM) has changed over the last decades, mainly because of the introduction of nucleoside analogues and of rituximab while novel agents such as bortezomib have been recently introduced. We performed an analysis to investigate whether the outcome of patients with WM has improved over the last years, compared to that of patients who started treatment before new drugs became widely available, especially as part of the frontline treatment. We analyzed 345 symptomatic patients with WM: 130 who initiated treatment before and 215 who started treatment after January 1, 2000. Patients who started treatment in the latter group were older and had more often elevated beta2-microglobulin but the other characteristics were similar between the two groups. Most patients who started treatment before January 1, 2000 were treated upfront with alkylating agent-based regimens and most patients who started treatment after January 1, 2000 received rituximab-based regimens as initial treatment. Objective response (63 and 59%, respectively) and median overall survival, OS, (106.5 months for Group A and is estimated at 94 months for Group B, P = 0.327) were similar. There was also no difference regarding OS or cause specific survival (CSS) in each risk group according to IPSSWM. Our observation may be explained by the indolent course of WM in several patients and by the lack of profound cytoreduction in patients with high-risk disease. Possible differences in the 15- or 20-year survival rate between the two groups may be detected with further follow-up of these patients.
Waldenström's macroglobulinemia is characterized by a protracted course in most patients and the median survival may be long. However, a subset of patients may present with more aggressive disease that is associated with short survival. In order to better characterize these "poor-risk" patients, we identified patients who died within 2 years from the initiation of front-line treatment. These patients were older and had more often features of aggressive disease, such as elevated LDH and low serum albumin than the standard-risk population. Furthermore, only a minority of poor-risk patient had a response to initial therapy. However, conventional clinical factors or even the lack on response could not adequately identify poor-risk patients, indicating the need for novel molecular or other markers that would be able to effectively recognize patients at greatest need for aggressive therapies.
Spanoudakis E, Papoutselis M, Kotsianidis I, et al., 2010, Over Expression of RANKL In Invariant NKT Cells Is Characteristic of Active Myeloma but Not of MGUS or Asymptomatic Myeloma, Pages: 1650-1651, ISSN: 0006-4971
Spanoudakis E, Papoutselis M, Kotsianidis I, et al., 2010, Over-Expression of RANKL In Invariant NKT Cells Is Characteristic of Active Myeloma but Not of MGUS or Asymptomatic Myeloma., 52nd Annual Meeting of the American-Society-of-Hematology (ASH), Publisher: AMER SOC HEMATOLOGY, Pages: 1650-1651, ISSN: 0006-4971
Patel B, Terpos E, Todd J, et al., 2010, Reduced bone mineral density and high bone turnover in long-term survivors of stem cell transplantation, 36th Annual Meeting of the European-Group-for-Blood-and-Marrow-Transplantat/9th Meeting of the EBMT Data-Management-Group/26th Meeting of the EBMT Nurses Group/2nd EBMT Qual Management Meeting, Publisher: NATURE PUBLISHING GROUP, Pages: S102-S103, ISSN: 0268-3369
Terpos E, Sezer O, Croucher PI, et al., 2009, The use of bisphosphonates in multiple myeloma: recommendations of an expert panel on behalf of the European Myeloma Network, ANNALS OF ONCOLOGY, Vol: 20, Pages: 1303-1317, ISSN: 0923-7534
Spanoudakis E, Hu M, Naresh K, et al., 2009, Regulation of multiple myeloma survival and progression by CD1d, Blood, Vol: 113, Pages: 2498-2507-2498-2507
Down-regulation of conventional human leukocyte antigen (HLA) class I and II molecules from the surface of tumor cells is an important mechanism for tumor immune evasion, survival, and progression. Whether CD1d, a nonconventional, glycolipid-presenting HLA class I–like molecule instructing the function of the immunoregulatory invariant NKT cells can affect tumor cell survival is not known. Here we show that CD1d is highly expressed in premalignant and early myeloma, but with disease progression its expression is reduced and eventually in advanced stages and myeloma cell lines is lost altogether, suggesting that CD1d impacts negatively on myeloma cell survival. Consistent with this, engagement of CD1d by anti-CD1d monoclonal antibodies (mAbs) induces cell death of myeloma cell lines with restored CD1d expression and primary myeloma cells. Cell death induced by monoclonal antibody engagement of CD1d is associated with overexpression of proapoptotic Bax and mitochondrial membrane potential loss but it is caspase-activation independent; in addition, it requires the cytoplasmic tail but not the Tyr residue critical for lysosomal sorting of CD1d. Finally, anti-CD1d cooperates with antimyeloma agents in the killing of myeloma cells. Thus, this work provides evidence linking a novel function of CD1d in the regulation of cell death with tumor survival and progression in humans.
Spanoudakis E, Hu M, Naresh K, et al., 2008, Regulation of Multiple Myeloma Survival and Progression by CD1d., 50th Annual Meeting of the American-Society-of-Hematology, Publisher: AMER SOC HEMATOLOGY, Pages: 940-940, ISSN: 0006-4971
Terpos E, 2008, Bortezomib directly inhibits osteoclast function in multiple myeloma: Implications into the management of myeloma bone disease, LEUKEMIA RESEARCH, Vol: 32, Pages: 1646-1647, ISSN: 0145-2126
Sterz J, von Metzler I, Hahne J-C, et al., 2008, The potential of proteasome inhibitors in cancer therapy, EXPERT OPINION ON INVESTIGATIONAL DRUGS, Vol: 17, Pages: 879-895, ISSN: 1354-3784
Terpos E, Roussou M, Dimopoulos M-A, 2008, Bortezomib in multiple myeloma, EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY, Vol: 4, Pages: 639-654, ISSN: 1742-5255
Terpos E, Sezer O, 2008, Reply to 'Proteasome inhibition therapies in childhood cancer' by Zaman et al., LEUKEMIA, Vol: 22, Pages: 884-885, ISSN: 0887-6924
Terpos E, 2008, Have myeloma cells osteoclast-like activity? Implications into the pathogenesis of myeloma bone disease, LEUKEMIA RESEARCH, Vol: 32, Pages: 521-522, ISSN: 0145-2126
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