A. Symeonidis | University of Patras (original) (raw)

Papers by A. Symeonidis

Leukemia & Lymphoma, 2007

Renal failure (RF) is a common and severe complication of patients with multiple myeloma (MM). Th... more Renal failure (RF) is a common and severe complication of patients with multiple myeloma (MM). The purpose of our study was to assess the incidence of RF in a contemporary series of newly diagnosed patients with MM, its association with specific clinical and laboratory features, and its impact on patients&amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; outcome. Over the last decade, 756 newly diagnosed symptomatic patients with MM were included in our database. Renal failure, defined as a serum creatinine &amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;or= 2 mg/dl at the time of diagnosis, was seen in 21% of patients. Multiple parameters were associated with RF, but logistic regression analysis showed that RF was independently associated only with International Staging System and Bence Jones proteinuria. The presence of RF was associated with a trend for higher early death rate but with a similar response to primary therapy. The median survival of patients with RF was 19.5 months versus 40.4 months for patients without RF (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). Several variables were associated with impaired survival by univariate analysis. When multivariate analysis was performed the independent variables were poor performance status, thrombocytopenia, advanced age, high LDH and elevated serum beta2 microglobulin but not high creatinine. When corrected for stage, renal failure had no impact on survival.

Blood, Nov 16, 2007

Introduction: An ISSWM was recently proposed (Morel et al, ASH 2006), which was based on a large ... more Introduction: An ISSWM was recently proposed (Morel et al, ASH 2006), which was based on a large number of patients treated primarily with alkylating agents and /or nucleoside analogues. The ISSWM based on 5 adverse covariates wich defined 3 risk groups: low, intermediate and high risk with 5-years survival rates of 87%, 68% and 36% respectively. In our current analysis, we assessed the impact of this system in patients with WM who received primary treatment with rituximab-based regimens. Patients and methods: Ninety-three previously untreated, symptomatic patients who received treatment either with single agent rituximab (21 patients) or with the combination of dexamethasone, rituximab, and cyclophosphamide (72 patients) were classified according to the ISSWM, which is based on 5 adverse covariates: age&amp;amp;amp;amp;amp;amp;gt; 65 years, hemoglobin ≤11.5 g/dl, platelet count ≤ 100 x 109/L, β2- microglobulin &amp;amp;amp;amp;amp;amp;lt;3mg/L, serum monoclonal protein concentration &amp;amp;amp;amp;amp;amp;gt;70g/L. Low risk is defined by the presence of ≤ 1 adverse characteristics except age, high risk by the presence of &amp;amp;amp;amp;amp;amp;gt;2 adverse characteristics and intermediate risk by the presence of 2 adverse characteristics or age &amp;amp;amp;amp;amp;amp;gt;65 years. Results: The disease features of the 93 patients were typical of symptomatic WM: age &amp;amp;amp;amp;amp;amp;gt; 65 years in 63%, males 65%, B-symptoms in 22%, splenomegaly in 29%, lymphadenopathy in 34%. 15% of patients were rated as low risk, 65% as intermediate risk and 20% as high risk. Criteria for initiation of therapy included cytopenia, hyperviscosity, constitutional symptoms, organomegaly or IgM-related disorders. Overall, 62% of patients were alive at 6 years. Median survival was not reached for low and intermediate risk and was 38 months for high risk patients (p=0.006). There was a clear separation of the survival curves in the three groups. At the time of last follow-up the percentage of patients alive was 100%, 82% and 58% for patients classified as low, intermediate and high-risk group respectively. Conclusions: The recently proposed ISSWM is applicable in patients with WM who receive primary treatment with rituximab-based regimens and may serve as a basis to compare outcomes in different studies.

Quality of Life Research, 2020

Purpose To evaluate health-related quality of life (HRQoL) and satisfaction with iron chelation t... more Purpose To evaluate health-related quality of life (HRQoL) and satisfaction with iron chelation therapy (ICT) of patients with transfusion-dependent β-thalassemia (TDT) managed under routine care conditions. Patients and methods This was an observational, multicenter, cross-sectional study conducted in three hospital-based Thalassemia Units of Western Greece. Patients confidentially completed the 36-item short-form (SF-36) and the "satisfaction with ICT" (SICT) instruments to assess HRQoL and ICT satisfaction respectively. Results One hundred and thirty-one adult TDT patients [74 female, median (IQR) age: 41 (36-47) years] were enrolled. Eighty patients (61.1%) were receiving parenteral ICT, with or without oral chelators (Group I), whereas 51 (38.9%) were only receiving oral ICT (Group II). The median SF-36 physical component summary and mental component summary scores were 76.3 and 75.7 among Group I, and 76.9 and 74.5 among Group II patients, not differing between the two groups. In their majority, Group I (84.6%) and Group II (92.9%) patients reported preferring oral ICT. Moreover, Group I patients reported greater perceived ICT effectiveness (median SICT score: 4.3 versus 4.2; p = 0.039), whereas patients receiving deferasiroxcontaining ICT reported higher treatment acceptance (median SICT score: 4.0 versus 3.6, p = 0.038) and greater satisfaction with the burden of their ICT (median SICT score: 4.4 versus 3.9, p = 0.033). Conclusion TDT patients prefer to receive oral ICT and are more satisfied of the burden of deferasirox-containing ICT, even though those receiving parenteral ICT are more satisfied by the effectiveness of their treatment. No differences in HRQoL were not noted between patients receiving parenteral versus oral ICT.

Annals of Oncology, 2003

The combination of vincristine and doxorubicin administered as a continuous infusion via an indwe... more The combination of vincristine and doxorubicin administered as a continuous infusion via an indwelling catheter together with intermittent high-dose dexamethasone (VAD) is an effective primary treatment for patients with symptomatic multiple myeloma. In order to avoid the need for an indwelling catheter, which imposes logistic problems for outpatient administration, several phase II studies have explored the feasibility and efficacy of VAD-like outpatient regimens. We designed a prospective randomized study to compare the objective response rates of two VAD-like outpatient regimens as primary treatment for symptomatic patients with multiple myeloma. Patients were entered in a randomized study regardless of age, performance status and renal function. One hundred and twenty-seven patients received VAD bolus, which consisted of vincristine 0.4 mg i.v., doxorubicin 9 mg/m(2) i.v. and dexamethasone 40 mg p.o. daily for four consecutive days and 132 patients received VAD doxil, which consisted of vincristine 2 mg i.v. and liposomal doxorubicin 40 mg/m(2) i.v. on day 1 and dexamethasone 40 mg p.o. daily for 4 days. The two regimens were administered every 28 days for four courses and in courses 1 and 3, in both arms, dexamethasone was also given on days 9-12 and 17-20. An objective response was documented in 61.4% and 61.3% of patients treated with VAD bolus and VAD doxil, respectively. Hematological and non-hematological toxicities were mild or moderate and equally distributed between the two treatment arms with the exception of alopecia, which was more common after VAD bolus, and of palmar-plantar erythrodysesthesia, which was more common after VAD doxil. Our multicenter trial, which included an unselected patient population, indicated that both VAD bolus and VAD doxil can be administered to outpatients and can provide an equal opportunity of rapid response in many patients with multiple myeloma.

Annals of Hematology, 2002

The aim of this prospective study was to determine whether treatment with a combination of GM-CSF... more The aim of this prospective study was to determine whether treatment with a combination of GM-CSF and erythropoietin (rhEpo) can improve the anemia associated with low risk myelodysplastic syndrome (MDS), namely refractory anemia (RA), RA with ring sideroblasts (RAS), and RA with excess of blasts (RAEB) with bone marrow blasts less than 10%. Eligibility criteria included an Hb level of less than 10.5 g/dl for newly diagnosed patients, or symptomatic anemia. GM-CSF was given at a dose of 3 g/kg s.c. on days 1-2, rhEpo at a dose of 60 U/kg s.c. on days 3-5. No treatment was given on days 6-7. Patients were followed-up with full blood count on a weekly basis. The treatment was repeated for a total of 6 weeks. At that time, if a rise in Hb above 1.5 g/dl had not been achieved, the dose of rhEpo increased to 120 U/kg. Post-treatment evaluation was performed at the completion of 12 weeks. Erythroid response was defined as good (GR), if an increase in untransfused Hb values above 2 g/dl or a 100% decrease in red blood cell transfusion requirements, over the treatment period was observed, while an increase in untransfused Hb values 1-2 g/dl or a Ͼ50% decrease in transfusion requirements, were considered as partial response. Responders continued to receive the same treatment until disease progression. Nineteen patients (13 male and six female) with a median age of 69 years were enrolled in the study. The FAB subtypes were: RA one case, RAS eight cases and RAEB 10 cases. Ten of 19 patients (52.6%) responded to the treatment: 7/19 (36.8%) achieved a GR and 3/19 (15.8%) a PR. Six of eight (75%) patients with RAS, one case with RA and 3/10 (30%) of cases with RAEB responded to treatment. Pretreatment serum epo levels were generally low (less than 200 Mu/ml) in responding patients. At the completion of the initial 12 weeks, 8/12 responding patients (5 RAS, 2 RAEB and 1 RA) continued to receive the same treatment. All responding patients with RAS continued to show an erythroid response in a time period from 3 to 24 months, whilst one patient with RA and two with RAEB did not have a continuing response at 2, 4 and 12 months, respectively. The above data suggest that the combination of rhEpo and GM-CSF should be recommended in all cases with RARS. However, the clear indication of this combination for other patients with MDS remains to be determined.

Leukemia Research, 2013

Developing a flow cytometric maturation/differentiation index of the bone marrow for the diagnosi... more Developing a flow cytometric maturation/differentiation index of the bone marrow for the diagnosis of myelodysplastic syndromes (MDS)
E. Verigou1, N. Smyrni1, G. Kolliopoulou1, E. Hala1, P. Lampropoulou1, G. Theodorou1, F. Kalogianni2, P. Zikos2, I. Starakis3, E. Solomou3, M. Karakantza1, A. Symeonidis1. 1Hematology Division Dept of Internal Medicine, Peripheral University Hospital of Patras, Patras, Greece; 2Hematology Division, St Andrew’s General Hospital of Patras, Patras, Greece; 3Internal Medicine, Peripheral University Hospital of Patras, Patras, Greece.
Background: Establishing the diagnosis of MDS is a challenging task, due to disease heterogeneity. Morphology remains the gold standard, but dysplastic features can often be misleading and differential diagnosis of MDS and MDS-like cytopenias is intriguing. Bone marrow (BM) immunophenotype has not been incorporated in the diagnostic criteria of MDS, although it may be useful, especially in disputed cases of low-risk MDS.
Introduction: We hypothesize that, BM myeloid cells exhibit immunophenotypic abnormalities, discriminating true from pseudoMDS, as well as maturation and differentiation blocks rather than marrow failure, and created a parametric index of BM normal granulopoietic capacity.
Purpose: We aimed to establish a BM maturation/differentiation index, thus maximi-zing the diagnostic utility of Flow Cytometry data, and simplify their interpretation, by quantifying antigenic patterns, based on mathematical modeling rather than, on conventional sequential biparametric analysis.
Materials and Methods: BM samples from 104 subjects were analysed for CD45PC7, CD11bPC5, CD16FITC and CD13PE expression (Beckman Coulter, FC500 flow cytometer). Sixty-eight patients had MDS (40 low risk, 28 high risk) and 26 patients had another diagnosis (ITP, chronic idiopathic neutropenia, systemic lupus erythema-tosus, LGL leukemia, age-related cytopenias, aplastic anemia, myelofibrosis etc). Moreover, 10 BM samples of patients with post-MDS acute myeloid leukemia (AML) were analyzed.
Results: CD16 and CD11b antigen expression pattern was chosen for their reproduci-bility and biological significance. Combining the percentage ratio of the regions O (maturing and differentiated myeloid cells) and N (myeloid precursors/ immature cells, Fig. 1), with a 3-dimensional space representing the distribution of maturing cells in a 3D plot of fluorescence levels of CD16, CD11b and CD45, we resulted in HeSK* ratio as follows:
x CD11b 0 y C D16 0 z C D45 neutro p0
10^6 pN
where x is the median of CD11b in region O, y is the median of CD16 in region O, z is the median of CD45 in region neutro, pO is the percentage of region O in the total CD11b/CD16 diagram gated in neu
Figure 2. HeSK/(%) blasts.
tro, pN is the percentage of region N in the total CD11b/CD16 gated
in neutro and 106 is an empirical parameter. The ratio could quantify
the abnormal differentiation profile of maturing myeloid cells and
distinguish MDS from non-MDS samples with high statistical significance (Kruskal-Wallis test, p<0.0001, Fig. 2). Descriptive statistics
are shown in Table 1.
Conclusions: HeSK correlated with morphological findings and highlights cases of clinical interest. Our future goal is to examine the behavior of antigen expression (as captured in HeSK) before and after
therapy, estimate the prognostic value of the ratio and amplify its diagnostic utility.
*HeSK: Authors’ name acronyms.

Leukemia Research, 2011

s of the 11th International Symposium on Myelodysplastic Syndromes (MDS) 18 May 2011 21 May 2011 ... more s of the 11th International Symposium on Myelodysplastic Syndromes (MDS) 18 May 2011 21 May 2011 Oral Presentations / Leukemia Research 35 (2011) S14–S26 S25 66 Allogeneic stem-cell transplantation in chronic myelomonocytic leukemia (CMML): Factors affecting transplantation outcome. A study of the CLWP of the EBMT A. Symeonidis, A. van Bietsen, G. Mufti, J. Finke, D. Beelen, M. Bornhaeuser, H. Greinix, J.P. Jouet, L. Volin, R. Schwerdtfeger, T. de Witte, N. Kroeger. Hematology Division, Dept of Internal Medicine, University of Patras Medical School, Patras, Greece; Dept of Medical Statistics and Bioinformatics, Chronic Leukemias Working Party of the EBMT, Leiden, The Netherlands; Dept of Hematological Medicine, GKT School of Medicine, London, UK; Dept of Medicine, Hematology, Oncology, University of Freiburg, Freiburg, Dept of Bone Marrow Transplantation, University Hospital of Essen, Essen, Medizinische Klinik und Polyklinik I, Universitaetsklinikum Dresden, Dresden, Germany; Klinik fuer Innere Medizin I, Medizinische Universitaet Wien, Vienna, Austria; Service des Maladies du Sang, Hopital Claude Huriez, Lille Cedex, Lille, France; Division of Hematology, Dept of Medicine, Helsinki University Central Hospital, Helsinki, Finland; KMT Zentrum, Deutsche Klinik fuer Diagnostik, Wiesbaden, Germany; Dept of Hematology, Radboud University Nijmegen, Nijmegen, The Netherlands; Bone Marrow Transplantation Centre, University Hospital Eppendorf, Hamburg, Germany According to WHO classification CMML is characterized, first, as dysplastic or proliferative and second, as type-1 or type-2. Results of allogeneic stem-cell transplantation (allo-SCT) in CMML are usually pooled together with other MDS. We retrospectively analyzed transplantation outcome in 489 patients with CMML from the EBMT database (females 160, males 329, median age 52.7 years, range 19.5–75.4 years). Among 145 patients, 67 had CMML-dysplastic and 78 CMML-proliferative, whereas among 214 patients with known subtype, 87 had type-1 (40.6%), 32 had type-2 (15%) and 95 had evolved to AML (44.4%). Conditioning was standard in 249 (55.7%) and reduced-intensity in 198 (44.3%). Donors were HLA-identical siblings (245~50.1%), other related (23~4.7%) or unrelated ones (221~45.2%). Disease status at allo-SCT was complete remission (CR) in 108 patients (22.1%), no-CR in 331 (67.7%) and unknown in 50 (10.2%). Stem cell source was bone marrow in 125 (25.6%) and peripheral blood (PBSC) in 365 (74.4%). Engraftment was successful in 432/460 patients (93.9%) and unknown in 29. Grades 0–1 acute GVHD was reported in 291/448 evaluable patients (65%), grades 2–4 in 149 (33.3%) and was unknown in 8. Chronic GVHD was reported in 102/197 patients (limited 49, extensive 53). At the time of this analysis 224 patients were alive (45.8%), of whom 198 (40.5%) were disease-free and 120 (24.5%) had relapsed. Among 265 deaths, 95 were disease-related (35.8%), 145 transplant-related (54.7%) and 25 other cause-related (9.4%). The probability of nonrelapse mortality at 4 years was 35% and it was lower in female to female allo-SCT (p =0.069). Patients with abnormal cytogenetics had higher risk for relapse (p = 0.017) and for death after relapse (p = 0.03). Patients transplanted in CR had lower probability for non-relapse death (p = 0.006) and longer RFS and OS (p =0.010 and p=0.018 respectively). Kaplan–Meier estimates for OS of the whole group was 46.7 months (95% Confidence Interval 38.1– 55.2 months). Kaplan-Meier estimates for RFS was longer in PBSC recipients (p = 0.006). In multivariate analysis the only significant prognostic factor for OS was disease status at SCT (CR vs noCR, p = 0.010). Analysis also included interval from diagnosis to transplant, dysplastic vs proliferative and type-1 vs type-2 disease, intensity of the conditioning, donor matching, cytogenetics, stemcell source, T-cell depletion, administration of total body irradiation, grading of acute and chronic GVHD and the year of allo-SCT. Allo-SCT remains a promising treatment option for patients with CMML and patients should preferably be referred to allo-SCT after achieving the best possible remission status. 67 Response to ESA treatment in patients with MDS: Determination of a predictive score, from a retrospective analysis of 669 patients A. Symeonidis, P. Zikos, A. Galanopoulos, I. Kotsianidis, A. Kouraklis, E. Terpos, M. Protopapa, H. Papadaki, V. Lambropoulou, A. Aktypi, P. Bakarakos, S. Michalopoulou, A. Anastasiadis, E. Michalis, N. Zoumbos. Hematology Division, Dept of Internal Medicine, University of Patras Medical School, Hematology, St Andreas Hospital of Patras, Patras, Dept of Hematology, G. Gennimatas General Hospital of Athens, Athinai, Dept of Hematology, Democritus Thrace University, Alexandroupolis, Dept of Medical Therapeutics, National and Kapodistrian University of Athens, Athinai, Dept of Hematology, General Hospital of Serres, Serres, Dept of Hematology, University of Crete School of Medicine,…

Clinical Lymphoma and Myeloma, 2009

Introduction: Novel therapies for myeloma have significantly improved overall survival in recent ... more Introduction: Novel therapies for myeloma have significantly improved overall survival in recent years for both newly diagnosed patients and those with relapsed disease. A Nurse Leadership Board (NLB) of oncology nurses from leading US cancer centers and community practices who care for myeloma patients was created by the International Myeloma Foundation in recognition of the essential role nurses play in patient care. The NLB published the first comprehensive guidelines for managing novel therapy-associated side effects, including myelosuppression, thromboembolic events, peripheral neuropathy, and gastrointestinal disturbances as well as steroid-associated side effects because novel agents are frequently prescribed in combination with steroids. NLB members recognize that because myeloma patients live longer, they experience the same comorbidities as other individuals in their age group as well as myeloma therapy-related comorbidities. Further, barriers to preventative health maintenance exist from the perspective of both practitioner and patient. Lack of preventative medicine results from time constraints, lack of knowledge regarding current guidelines and their applications, questions about relevance to myeloma patients, and healthcare costs. Methods: The NLB Long-Term Care (LTC) Plan Task Force is using evidence-based practice to generate a Health Maintenance Schedule to preserve the health and wellness of myeloma patients, taking into account the effects of myeloma, past and current therapies, and overall risk based on age, sex, and lifestyle. The NLB determined that basing this approach on organ systems would be crucial to improved overall survival and quality of life. Results: The LTC Guidelines will address how myeloma, treatments, and patient-specific characteristics affect these areas of concern: renal disease, sexuality and sexual dysfunction, bone metabolism, safety and functional mobility, and health promotion and disease prevention. The NLB will also develop recommendations for schedules of evaluations and evidenced-based interventions. Conclusion: Incorporating all levels of preventative medicine from screening through treatment of sequelae will enable clinicians and patients to optimize therapy by preventing or adequately treating comorbid conditions that might otherwise limit future therapeutic options. Ultimately, the NLB will disseminate this information to those within in the community who can affect the most change: patients and their caregivers and healthcare providers.

Biology of Blood and Marrow Transplantation, 2011

Annals of Hematology, 2006

Acta Haematologica, 1992

One of the major determinants of erythrocyte survival is membrane deformability, and an important... more One of the major determinants of erythrocyte survival is membrane deformability, and an important intrinsic parameter of membrane deformability is the shear elastic modulus (mu) with higher mu values corresponding to increased membrane rigidity. Using a micropipette technique, we determined the shear elastic modulus of erythrocytes from 21 patients with myelodysplastic syndromes (MDS). Ten thalassemic patients and 15 healthy subjects served as controls. The shear elastic modulus of MDS erythrocytes was very significantly increased in all the patients studied, reflecting the rigidity of the membrane; the value of mu was also significantly higher in comparison with thalassemic cells. These data point to a fundamental change in the mechanical properties of the erythrocyte membrane in MDS. Biochemical studies of the membrane composition are clearly needed.