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ABSTRACT: Essential thrombocythemia is characterized by persistent elevation and functional disturbances of platelets. Both the platelet function analyzer-100 (PFA-100) collagen-epinephrine (CEPI) cartridge and aggregometry with epinephrine are considered sensitive and valid methods in detecting abnormal platelet function in essential thrombocythemia. We attempted to confirm that restoration of abnormal platelet function results from platelet count reduction in essential thrombocythemia, by using these two methods. Thirty-nine essential thrombocythemia patients were divided into two groups on the basis of their platelet count. Group A participants (n = 20) exhibited platelet counts greater than 500 × 10/l, whereas group B participants (n = 19) had platelet counts below this limit. Hematological parameters, plasma von Willebrand factor (vWF) antigen and activity levels were assessed. Platelet function was analyzed by the PFA-100 and light transmission aggregometry with epinephrine, collagen, and ADP. The point mutation JAK2 V617F was identified and its effect on platelet function tests was also investigated. By using logistic regression analysis, white blood cell count, vWF activity level, and the measurements of aggregation in response to epinephrine were significantly different between the two groups. Epinephrine-induced aggregation retained the statistical significance in the multivariable procedure (P : 0.002). PFA-100 CEPI closure times were lower - but not statistically significant - in group B. Neither the JAK2 V617F positivity nor different cytoreductive treatments had any influence on ex-vivo platelet function tests. Our findings demonstrate normalization of platelet function resulting from platelet count reduction in essential thrombocythemia and reinforce the concept of lowering platelet counts in these patients.
Blood coagulation & fibrinolysis: an international journal in haemostasis and thrombosis 09/2011; 22(6):457-62. · 1.25 Impact Factor
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Efstathios Kastritis,
Marie-Christine Kyrtsonis,
Evdoxia Hatjiharissi,
Argiris Symeonidis,
Eurydiki Michalis,
Panagiotis Repoussis,
Konstantinos Tsatalas,
Michael Michael,
Anastasia Sioni,
Zafiris Kartasis, [......],
Elissavet Vervesou,
Konstantinos Konstantopoulos,
Garyfalia Kokkini, Athanasios Zomas,
Paraskevi Roussou,
Nikolaos Anagnostopoulos,
Theofanis Economopoulos,
Evangelos Terpos,
Konstantinos Zervas,
Meletios A Dimopoulos
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ABSTRACT: 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.
American Journal of Hematology 06/2011; 86(6):479-83. · 4.67 Impact Factor
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Efstathios Kastritis,
Maria Gavriatopoulou,
Marie-Christine Kyrtsonis,
Michael Michael,
Evdoxia Hadjiharissi,
Argiris Symeonidis,
Eurydiki Michalis,
Panagiotis Repoussis,
Konstantinos Tsatalas,
Anastasia Sioni, [......],
Elissavet Vervesou,
Konstantinos Konstantopoulos,
Garyfalia Kokkini, Athanasios Zomas,
Paraskevi Roussou,
Nikolaos Anagnostopoulos,
Theofanis Economopoulos,
Evangelos Terpos,
Konstantinos Zervas,
Meletios A Dimopoulos
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ABSTRACT: 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.
Clinical lymphoma, myeloma & leukemia 02/2011; 11(1):127-9.
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Evangelos Terpos,
Eirini Katodritou,
Maria Roussou,
Anastasia Pouli,
Eurydiki Michalis,
Sosana Delimpasi,
Agapi Parcharidou,
Zafiris Kartasis, Athanasios Zomas,
Argiris Symeonidis,
Nora-Athina Viniou,
Nikolaos Anagnostopoulos,
Theofanis Economopoulos,
Konstantinos Zervas,
Meletios A Dimopoulos
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ABSTRACT: High serum lactate dehydrogenase (LDH) is associated with features of advanced disease and inferior survival in multiple myeloma. It is however unclear whether LDH adds to the prognostic value of International Staging System (ISS) and whether it retains its prognostic significance in patients who are exposed to novel agent-based therapies.
To address these issues we analyzed 996 consecutive symptomatic patients who were included in the database of the Greek Myeloma Study Group and received frontline treatment between January 1, 1995 and December 31, 2008.
The median overall survival (OS) of all patients was 40 months with a clear improvement in those who started treatment after January 1, 2000 (49 vs. 31 months; P < 0.01). A multivariate model showed that LDH, ISS, performance status, age and platelet counts had an independent prognostic value for OS (P < 0.001 for all parameters). The median OS of patients with high (11% of patients) and normal LDH was 15 vs. 44 months (P < 0.001). High LDH was associated with inferior OS within all ISS groups: 22 vs. 76 months for high and normal LDH groups, respectively, in ISS-1 (P < 0.01); 11 vs. 40 months in ISS-2 (P < 0.001) and 17 vs. 27 months in ISS-3 (P < 0.01). The median OS of high and normal LDH groups among patients who received novel agents was 21 vs. 51 months, respectively (P < 0.001).
Lactate dehydrogenase is a readily available and inexpensive variable, which has a major impact on the survival of myeloma patients even when they belong to a low or intermediate ISS subgroup and even when they receive novel agent-based therapies.
European Journal Of Haematology 08/2010; 85(2):114-9. · 2.61 Impact Factor
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Efstathios Kastritis,
Marie-Christine Kyrtsonis,
Evdoxia Hadjiharissi,
Argyris Symeonidis,
Evridiki Michalis,
Panagiotis Repoussis,
Constantinos Tsatalas,
Michael Michael,
Anastasia Sioni,
Zafiris Kartasis, [......],
Maria Gavriatopoulou,
Efstathios Koulieris,
Dimitra Gika, Athanasios Zomas,
Paraskevi Roussou,
Nikolaos Anagnostopoulos,
Theophanis Economopoulos,
Evangelos Terpos,
Konstantinos Zervas,
Meletios A Dimopoulos
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ABSTRACT: The recently proposed, ISSWM staging system for symptomatic patients with WM was based on patients treated with alkylating agents and nucleoside analogs and has not been externally validated nor has been validated for cause-specific survival (CSS). We independently validated ISSWM both for overall survival (OS) and for CSS and assessed whether addition of elevated serum LDH may add to the strength of ISSWM in 335 patients treated upfront mainly with alkylating agents (43%), and rituximab-based therapies (47%). ISSWM could discriminate three groups with significantly different OS and CSS (p<0.01 for both). High serum LDH was predictive of shorter OS and CSS (p<0.01). The combination of high risk according to ISSWM and elevated serum LDH identified a subset of patients for whom innovative treatment approaches are needed.
Leukemia research 05/2010; 34(10):1340-3. · 2.36 Impact Factor
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Efstathios Kastritis,
Konstantinos Zervas,
Panagiotis Repoussis,
Evridiki Michali,
Eirini Katodrytou, Athanasios Zomas,
Argiris Simeonidis,
Evangelos Terpos,
Sossana Delimbassi,
Amalia Vassou,
Dimitra Gika,
Meletios A Dimopoulos
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ABSTRACT: We analyzed 232 patients with previously untreated, symptomatic WM, of whom 10% were < or = 50 years of age and 21% were > 75 years of age. Disease features and response to treatment were similar among age groups. Patients > 75 years of age had significantly shorter survival (OS; 53 months vs. 113 months for those > 50-75 years vs. not reached for patients < or = 50 years of age; P < .001). Despite the fact that 33% of elderly patients died of causes unrelated to WM, disease-specific survival (DSS) was 72 months for patients > 75 years, 120 months for those > 50-75 years and not reached for patients < or = 50 years (P = .001). International Prognostic Scoring System for WM (IPSSWM) could discriminate 3 risk groups with significantly different OS or DSS. The addition of elevated serum lactate dehydrogenase in the IPSS improved the ability of IPSS to identify a group of patients with a significantly worse outcome (median survival, 55 months).
Clinical Lymphoma & Myeloma 02/2009; 9(1):50-2. · 1.13 Impact Factor
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Haematologica 09/2008; 93(9):1420-2. · 6.42 Impact Factor
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ABSTRACT: Waldenstrom's macroglobulinemia (WM) is a lymphoplasmacytoid lymphoma characterized by a relatively indolent course with median survival ranging from 5 years to 10 years in different series. Several clinical and laboratory variables have been associated with inferior survival, such as advanced age, hyperviscosity, presence of cytopenia, and hypoalbuminemia. Recent data indicate that serum 2-microglobulin (2M) might also be significant. The purpose of our study was to assess possible correlations of 2M with clinical and laboratory variables and to further evaluate its association with cause-specific and overall survival (OS) of patients with WM requiring treatment.
We analyzed 124 patients with WM with an available pretreatment value of 2M. Median age was 70 years (range, 28-89 years), and median survival was 105 months. Multiple clinical and laboratory parameters were evaluated for their possible correlation with OS.
Patients with older age, anemia, thrombocytopenia, hypoalbuminemia, and higher creatinine levels had significantly greater serum 2M levels. This variable was associated with impaired cause-specific survival and OS in the whole group of patients and in patients aged </= 70 years. More specifically, OS for all patients according to serum 2M > 4 mg/dL versus </= 4 mg/dL was 79 months versus 115 months (P = 0.01).
Our data provide further evidence that high 2M levels are an important parameter associated with inferior OS and cause-specific survival of patients with WM requiring treatment. This parameter may be used to stratify patients involved in prospective clinical trials.
Clinical Lymphoma & Myeloma 12/2006; 7(3):205-9. · 1.13 Impact Factor
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Meletios A Dimopoulos,
Athanasios Anagnostopoulos,
Evangelos Terpos,
Panagiotis Repoussis, Athanasios Zomas,
Eirini Katodritou,
Marie Christine Kyrtsonis,
Souzana Delibasi,
Amalia Vassou,
Anastasia Pouli,
Konstantinos Zervas,
Nikolaos Anagnostopoulos,
Alice Maniatis
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ABSTRACT: Fifty patients with multiple myeloma >or=75 years of age received primary treatment with melphalan (M) 8 mg/m(2) on days 1-4, dexamethasone (D) 12 mg/m2 on days 1-4 and 17-20 and thalidomide (T) 300 mg at bedtime on days 1-4 and 17-20. This regimen was repeated every 5 weeks for three courses. Patients without evidence of disease progression received nine additional courses of MDT, but without DT on days 17-20, every 5 weeks. Sixty-two percent of patients achieved a partial response and 10% a complete response. The median time to response was 2 months. The median time to progression for all patients was 21.2 months. Deep venous thrombosis and peripheral neuropathy each occurred in 9% of patients.
Haematologica 02/2006; 91(2):252-4. · 6.42 Impact Factor
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ABSTRACT: Rituximab is an active agent for the treatment of Waldenstrom's macroglobulinemia. However, many patients do not respond to this agent and several others develop secondary resistance. In order to identify clinical and laboratory parameters that could predict a higher likelihood for response, we evaluated 54 patients who were treated with single-agent rituximab. Twenty-four patients (44%)exhibited > or = 50% reduction of serum monoclonal protein. Previously untreated and pretreated patients had the same probability for response. Low response rates were noted in patients with serum monoclonal protein level > or = 40 g/L (17%) and serum albumin level < 35 g/L (14%). Furthermore, a multivariate analysis indicated that high serum monoclonal protein and low albumin were the dominant variables associated with shorter time to progression. The presence of 2, 1, or none of these variables was associated with median times to progression of 4 months, 11 months, and approximately 48 months, respectively. We conclude that patients with low levels of monoclonal protein and normal albumin are the best candidates for treatment with rituximab.
Clinical lymphoma 03/2005; 5(4):270-2. · 3.11 Impact Factor
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Athanasios Anagnostopoulos,
Dimitra Gika,
George Hamilos,
Konstantinos Zervas, Athanasios Zomas,
Anastasia Pouli,
Markela Zorzou,
Efstathios Kastritis,
Nikolaos Anagnostopoulos,
Anna Tassidou,
Dimitra Anagnostou,
Meletios-Athanasios Dimopoulos
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ABSTRACT: We evaluated the predictive value of several parameters, including the International Staging System (ISS) for myeloma, in patients with advanced disease treated with thalidomide-based regimens (TBR). We analyzed 119 patients, from 3 phase II studies. Patients with pretreatment beta2 microglobulin<3.5 mg/l and albumin 3.5 g/dl were scored ISS stage 1, patients with beta2 microglobulin<3.5 mg/l and albumin<3.5 g/dl or beta2 microglobulin 3.5-5.5 mg/l regardless of albumin levels were scored ISS stage 2, patients with beta2 microglobulin>5.5 mg/l ISS stage 3. ISS stage was 1, 2 and 3 in 45, 32 and 23% of patients respectively. Seventy-four patients (62%) achieved at least partial response. Median progression-free and overall survival were 8 months and 19.5 months respectively. ISS stage, serum LDH and performance status were independent predictive factors for survival. Based on these 3 variables a scoring system was developed with survival times of 38.1, 28.8 and 5.8 months for scores 0, 1 and 2 respectively. The ISS staging system was highly predictive for overall survival of patients with advanced myeloma treated with TBR. With the addition of performance status and serum LDH, a simple scoring system was developed which may help select patients likely to benefit from TBR.
Leukemia and Lymphoma 11/2004; 45(11):2275-9. · 2.58 Impact Factor
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Meletios A Dimopoulos,
George Hamilos, Athanasios Zomas,
Dimitra Gika,
Eleni Efstathiou,
Vassiliki Grigoraki,
Christos Poziopoulos,
Irini Xilouri,
Markela P Zorzou,
Nikolaos Anagnostopoulos,
Athanasios Anagnostopoulos
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ABSTRACT: Thalidomide is an oral agent with significant activity in one-third of patients with refractory myeloma. However, long-term continuous administration of thalidomide can be associated with significant side effects such as deep-vein thrombosis and peripheral neuropathy. Furthermore, it is not clear whether continuous administration of thalidomide is necessary for its antimyeloma effect. We performed a phase II study with a combination that was based on the intermittent administration of thalidomide.
A total of 53 patients with previously treated myeloma received cyclophosphamide 150 mg/m(2) p.o. every 12 h before meals on days 1-5, thalidomide 400 mg p.o. in the evening on days 1-5 and 14-18 and dexamethasone 20 mg/m(2) in the morning after breakfast on days 1-5 and 14-18 (CTD). The CTD combination was repeated every 28 days for three courses. Subsequently, responding patients were scheduled to receive maintenance treatment with monthly courses of CTD administered only for the first five days of each month.
On an intention-to-treat basis, 32 patients (60%) achieved a partial response with a median time to response of 1.5 months. Among the 43 thalidomide-naïve patients, 67% responded. Toxicities were mild or moderate and the cumulative incidence of deep-vein thrombosis and peripheral neuropathy was 4 and 2%, respectively. The median time to progression for responding patients was 12 months and the median overall survival for all patients was 17.5 months.
The oral, outpatient pulsed CTD regimen is associated with significant activity in patients with previously treated multiple myeloma. The incidence of deep-vein thrombosis and peripheral neuropathy appears to be lower than expected when thalidomide is being administered on a continuous basis.
The Hematology Journal 02/2004; 5(2):112-7. · 1.86 Impact Factor
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ABSTRACT: Waldenström's macroglobulinemia is a low-grade lymphoplasmacytoid lymphoma characterized by CD20 expression on malignant cells. Several studies have indicated that the anti-CD20 monoclonal antibody rituximab has activity against this disease. Thus, we performed a prospective study in which 17 previously untreated patients with symptomatic macroglobulinemia were treated with rituximab 375 mg/m2 intravenously for 4 weeks. Three months after completion of rituximab, patients without evidence of progressive disease received repeat 4-week courses of this agent. Six patients (35%) achieved a partial response after extended treatment with rituximab. Median time to response was 3 months. The median time to progression (TTP) for all patients was 13 months. One of 6 responding patients has progressed at 10 months, while the other 5 patients remain progression free with a follow-up range of > 22-40 months. Eight patients (47%) were rated as stable disease, and their median TTP was 9 months. Treatment with rituximab was well tolerated and was not associated with myelosuppression; one third of the patients experienced infusion-related toxicity, usually fever and chills of mild degree. Our prospective trial of extended rituximab therapy for previously untreated patients with Waldenström's macroglobulinemia indicates that this agent is active, well tolerated, and might be associated with a long period without the need for further treatment. Studies that will combine rituximab with chemotherapy or with other monoclonal antibodies might be of interest.
Clinical lymphoma 12/2002; 3(3):163-6. · 3.11 Impact Factor
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ABSTRACT: (99m)Tc-2-methoxyisobutylisonitrile ((99m)Tc-MIBI) scintigraphy has been suggested in multiple myeloma (MM) patients. According to the International Staging System (ISS), serum b2-microglobulin (Sbeta(2)M) and serum albumin (SA) are dominant predictive factors and different cut-off values of these factors can separate patients into various stages of the disease. The purpose of this study was to assess the relationship between ISS staging, by Sbeta(2)M and SA, and the (99m)Tc-MIBI scan findings. Twenty-five MM patients have been studied. Eighteen patients were at stage I, three at stage II and four at stage III of MM. (99m)Tc-MIBI scans were obtained and scored according to intensity (I) and extent (E) of the radiotracer uptake. A summed score (S) for the (99m)Tc-MIBI scan was calculated for each patient. A statistically significant negative correlation between E, I and S uptake scores versus the SA levels (P=0.004, 0.049 and 0.018 respectively), as well as a statistically significant positive correlation between E and S scores and the Sbeta(2)M levels (P=0.012 and 0.032) were detected. A statistically significant difference between the E and S uptake scores among the MM patients examined for every stage separately was also found (P=0.007 and 0.024 respectively). The gradual increase of the E and S scores across the three stages of MM was also significant (P=0.003 and 0.021 respectively), despite the relatively small number of patients in stages II and III. In seven patients who died at the end of the follow-up period all three scores were significantly increased as compared to the scores of the patients who remained alive at that time. In conclusion, this study provides additional evidence that (99m)Tc-MIBI scan not only reflects myeloma disease activity in bone marrow but it is also well correlated with the Sbeta(2)M and SA levels according to ISS.
Hellenic journal of nuclear medicine 9(3):177-80. · 0.81 Impact Factor
