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John Meletis

imeletis@cc.uoa.gr

Journal articles

2007
 
DOI   
PMID 
Athanassios Aessopos, Maria Kati, John Meletis (2007)  Thalassemia intermedia today: should patients regularly receive transfusions?   Transfusion 47: 5. 792-800 May  
Abstract: BACKGROUND: beta-Thalassemia is an inherited hemoglobin disorder characterized by reduced synthesis of beta-globin chain. The severity of clinical course distinguishes this heterogeneous disease in two main subtypes: thalassemia major (TM) and thalassemia intermedia (TI). TI has a later clinical onset with a milder anemia that does not require transfusions at least during the first few years of life. The clinical picture of TI patients who have not received transfusions or have occasionally received transfusions is dominated by the consequences of chronic hemolytic anemia, tissue hypoxia, and their compensatory reactions, such as bone deformities and fractures, extramedullary hemopoiesis, spleen and liver enlargement, hypercoagulability, and pulmonary hypertension. These complications, especially the latter two, are getting more frequent and severe over the years. Nowadays, although TI patients have almost no changes in the course of the disease, well-treated TM patients with regular transfusion-chelation therapy showed suppression of the anemia-related disorders in parallel to prolongation of life. The new oral iron chelators and the magnetic resonance imaging application for early detection of heart iron load are promising for further improvement on survival. CONCLUSIONS: Considering the current cost-benefit balance of regular treatment in TM as well as the frequency and severity of complications in TI, it seems that the majority of TI patients will be benefited if this kind of treatment is applied targeting prevention and not palliation of the anemia-induced complications.
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DOI   
PMID 
Athanasios Anagnostopoulos, Vangelis Eleftherakis-Papaiakovou, Efstathios Kastritis, Konstantinos Tsionos, Aristotelis Bamias, John Meletis, Meletios A Dimopoulos, Evangelos Terpos (2007)  Serum concentrations of angiogenic cytokines in Waldenstrom macroglobulinaemia: the ration of angiopoietin-1 to angiopoietin-2 and angiogenin correlate with disease severity.   Br J Haematol 137: 6. 560-568 Jun  
Abstract: Angiogenesis represents an essential step of disease progression in several haematological malignancies. Microvessel density is increased in 30% of patients with Waldenstrom macroglobulinaemia (WM), but there is very limited information regarding the role of angiogenic cytokines in this disease. Serum levels of vascular endothelial growth factor (VEGF), VEGF-A, angiogenin, angiopoietin (Ang)-1 and -2, and basic fibroblast growth factor (bFGF) were evaluated in 56 WM patients at different disease phases (24 untreated, 20 relapsed/refractory and 12 patients at remission) and 11 patients with immunoglobulin M type monoclonal gammopathy of undetermined significance (IgM-MGUS). All patients had increased levels of angiogenin, VEGF, VEGF-A, and bFGF compared with controls. The Ang-1/Ang-2 ratio was reduced in WM but not in IgM-MGUS patients. Angiogenin levels correlated with disease status: when compared with healthy subjects, patients with IgM-MGUS and untreated WM patients had increased angiogenin serum levels, which were higher in untreated WM patients than in MGUS. WM patients at remission had lower angiogenin serum levels compared with untreated patients, but these levels were increased again in active disease post-therapy. Angiogenin also correlated with albumin levels, while VEGF-A correlated with beta(2)-microglobulin (beta2M). Ang-1/Ang-2 ratio showed a strong, negative correlation with beta2M, and positive correlation with albumin, haemoglobin and lymphadenopathy. Our results indicate a potential use of angiogenin levels for follow-up in WM and angiogenic molecules as targets for the development of novel anti-WM agents.
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2006
 
PMID 
K Lilakos, N A Viniou, D Mavrogianni, T P Vassilakopoulos, M N Dimopoulou, E Plata, M K Angelopoulou, E Variami, N Stavrogianni, D Liapi, I Xilouri, A Galanopoulos, M Ageloudi, P Panayiotidis, M Voulgarelis, J Rombos, J Meletis, X Yataganas, G A Pangalis (2006)  FLT3 overexpression in acute promyelocytic leukemia patients without detectable FLT3-ITD or codon 835-836 mutations: a pilot study.   Anticancer Res 26: 2A. 1201-1207 Mar/Apr  
Abstract: BACKGROUND: Activating mutations of the FLT3 receptor tyrosine kinase are common in acute promyelocytic leukemia (APL) but have uncertain prognostic significance. Information regarding FLT3 expression levels in APL without FLT3 mutations is lacking. MATERIALS AND METHODS: Using RT-PCR, mutation analysis of the FLT3 gene, regarding internal tandem duplications (ITDs) and codon 835-836 point mutations, was performed and real-time PCR was carried out to determine the level of FLT3 expression in 11 APL patients at diagnosis and 5 in haematological remission with molecularly detectable disease. RESULTS: High levels of FLT3 transcript, at least a 10-fold increase compared to the normal controls, were found at diagnosis in all 3 mutated cases and in 2 patients without detectable FLT3 mutations. CONCLUSION: FLT3 overexpression can be documented in patients without FLT3 mutations. These patients might benefit from treatment using specific FLT3 tyrosine kinase inhibitors. Larger studies are needed to evaluate the clinical and biological significance of FLT3 overexpression in the absence of FLT3 mutations.
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PMID 
John Meletis, Nora Viniou, Evangelos Terpos (2006)  Novel agents for the management of myelodysplastic syndromes.   Med Sci Monit 12: 9. RA194-RA206 Sep  
Abstract: Therapeutic decisions in patients with myelodysplastic syndromes (MDS) are very complex. The dilemma that confronts the management of MDS is illustrated by the presence of only one agent (5-azacitidine), which has been approved by the U.S.A. Food and Drug Administration, with an indication for all subtypes of this disease and another one (lenalidomide) for the management of a specific MDS subgroup, the 5q-syndrome. Current classifications and prognostic systems do not take into account the considerable clinical heterogeneity of MDS or their diverse biology. Supportive care, low-intensity treatment, acute myeloid leukemia-type therapy, and stem cell transplantation (SCT) produce unsatisfactory results because patients continue to be exposed to the inherent complications of worsening cytopenias and leukemic transformation. Recent years have witnessed an evolution in our understanding of pathophysiology pathways in MDS. At the same time, many novel and targeted therapies are being investigated in clinical trials, offering patients the prospect of sustained benefit and changing the natural course of the disease. Hypomethylating agents, immunomodulatory drugs, and farnesyl-tranferase inhibitors have produced very promising results in terms of response and survival in MDS patients. This review summarizes all recent data on the role of novel agents and SCT in the treatment of patients with MDS in an attempt to better understand their possible therapeutic status in the management of these patients.
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DOI   
PMID 
Vassiliki Romanou, Peter Hatzinikolaou, Klio I Mavragani, John Meletis, George Vaiopoulos (2006)  Lupus erythematosus complicated by hemophagocytic syndrome.   J Clin Rheumatol 12: 6. 301-303 Dec  
Abstract: We report the case of a 28-year-old woman with systemic lupus erythematosus who, during a flare, suddenly developed febrile pancytopenia, hyperferritinemia, and abnormal liver function tests. Bone marrow aspiration confirmed hemophagocytic syndrome (HPS). Lupus-related HPS was diagnosed and the patient was treated with intravenous immunoglobulin, high-dose steroids, and cyclophosphamide with an excellent outcome. In febrile patients with lupus, pancytopenia together with very high ferritin levels should raise the suspicion of HPS and because this may be fatal, early bone marrow aspiration is mandatory for the diagnosis. The exclusion of concurrent infection as the cause of HPS is very important for the establishment of the right therapeutic strategy.
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2005
 
DOI   
PMID 
M Tsironi, S Deftereos, P Andriopoulos, D Farmakis, J Meletis, A Aessopos (2005)  Reversal of heart failure in thalassemia major by combined chelation therapy: a case report.   Eur J Haematol 74: 1. 84-85 Jan  
Abstract: In patients with thalassemia major (TM) who are non-compliant with long-term desferrioxamine (DFO) chelation, survival is limited mainly because of cardiac complications of transfusional hemosiderosis. Combined chelation therapy with DFO and deferiprone has maximized the efficacy of the therapy and reduced cardiological complications. The aim of this report is to present the results of this combination in a desperate case of heart failure.
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PMID 
Argirios Tsantes, Stefanos Bonovas, Stergios Tassiopoulos, Kalitsa Filioussi, Athina Vlachou, John Meletis, Stefanos Papadhimitriou, George Vaiopoulos (2005)  A comparative study of the role of erythropoietin in the pathogenesis of deficient erythropoiesis in idiopathic pulmonary fibrosis as opposed to chronic obstructive pulmonary disease.   Med Sci Monit 11: 4. CR177-CR181 Apr  
Abstract: BACKGROUND: Despite the severe derangement of gas exchange in the advanced stages of idiopathic pulmonary fibrosis (IPF), secondary erythrocytosis is either absent or much lower than is seen in chronic obstructive pulmonary disease (COPD) with comparable hypoxemia. This study investigates the differences in erythropoiesis between IPF and COPD, searching for the possible underlying mechanisms. MATERIAL/METHODS: The study included 32 patients with COPD, 18 patients with IPF, all with overt hypoxemia (PO(2) <65 mmHg), and 34 healthy controls. Erythrocytic parameters and serum erythropoietin (EPO) levels were assessed for all subjects. In a number of patients from both groups, the development of erythroid colonies grown from peripheral blood mononuclear cells was assayed in semisolid methylcellulose cultures and compared to cultures of control cells, in the presence of patient or control serum. RESULTS: Hb and serum EPO levels were significantly higher in the COPD group than in IPF patients and controls. However, the number of BFU-E colonies obtained from mononuclear cells of IPF patients was clearly higher than in COPD patients when the same culture medium was used. Unlike COPD sera, IPF sera induced a significant growth inhibition of erythroid bursts arising from mononuclear cells of both patients and controls. CONCLUSIONS: Our findings suggest a kind of ineffective erythropoiesis in IPF. Defective EPO production and inhibitory effect on erythropoiesis exerted by pro-inflammatory cytokines released from alveolar macrophages may be implicated in the suboptimal erythropoietic response. However, the possible involvement of other factors affecting erythropoiesis in IPF requires further investigation.
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DOI   
PMID 
Ersi Voskaridou, Maroussa Douskou, Evangelos Terpos, Alexandra Stamoulakatou, John Meletis, Akis Ourailidis, Ioannis Papassotiriou, Dimitris Loukopoulos (2005)  Deferiprone as an oral iron chelator in sickle cell disease.   Ann Hematol 84: 7. 434-440 Jul  
Abstract: Iron overload is not uncommon in sickle cell disease (SCD) and requires regular chelation therapy in several instances. The present study evaluates the effect of deferiprone in 15 adult patients with SCD (ten beta(s)/beta(0)thalassemia and five beta(s)/beta(s)) and iron overload. Deferiprone was given at a dose of 75 mg/kg daily for 12 months. The evaluation considered pre- and post-treatment values of serum ferritin, urinary iron excretion, and T2 values of liver and heart obtained by magnetic resonance imaging (MRI). Eleven patients had a liver biopsy prior to starting therapy to evaluate iron concentration (LIC). Twelve patients completed the study with satisfactory compliance. In ten of them (83.3%) the serum ferritin levels decreased significantly at the end of the trial; in eight patients (66.6%) the reduction of serum ferritin was accompanied by a significant increase of their liver T2 values. All patients had a significant increase of urinary iron excretion in response to the drug. Ferritin levels and liver T2 values correlated with liver iron concentration; on the contrary, ferritin levels and liver T2 values failed to show any correlation with heart T2 values. Heart T2 values did not also show any correlation with left ventricular ejection fraction. Deferiprone was well tolerated and did not cause any significant adverse effects. These results suggest that deferiprone may effectively decrease the iron deposition in patients with SCD; moreover, T2 MRI proves to be a reliable and rapid, noninvasive method for assessing the liver iron load in patients with SCD.
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2004
 
DOI   
PMID 
Athanasios Aessopos, Dimitrios Farmakis, Antonia Hatziliami, Christina Fragodimitri, Fotis Karabatsos, Jacqueline Joussef, Eftichia Mitilineou, Evanthia Diamanti-Kandaraki, John Meletis, Markisia Karagiorga (2004)  Cardiac status in well-treated patients with thalassemia major.   Eur J Haematol 73: 5. 359-366 Nov  
Abstract: OBJECTIVE: To assess cardiac status in a large group of patients with thalassemia major who had been treated in a standard way since their early infancy with intensive transfusions and deferoxamine chelation therapy and who had good compliance with this regimen. METHODS AND RESULTS: We assessed clinically and echocardiographically 202 thalassemia major patients aged 27.3 +/- 6.3 yr and 75 age and sex-matched healthy controls. Overt cardiac disease was encountered in 14 patients (6.9%), including 5 (2.5%) with congestive heart failure, aged 26-37 yr, and 9 with systolic left ventricular (LV) dysfunction, aged 23-37 yr. Ten patients (5.0%) had a history of pericarditis. Left atrial and LV diameters, LV mass and cardiac output were significantly higher in patients than in controls, while peripheral resistance and LV afterload were significantly lower. Relative LV wall thickness did not differ between patients and controls, but it was significantly lower in patients with overt cardiac disease compared to those without (P < 0.05). Restrictive LV filling was observed in 37.6% of patients and was significantly more frequent in cases with overt cardiac disease (P < 0.01). Pulmonary hypertension was practically absent. Hematological parameters and pulmonary artery pressure levels were not independently associated with the presence of overt cardiac disease. CONCLUSION: Strict lifelong adherence to the standard transfusion and deferoxamine therapy reduces considerably the occurrence of heart failure, LV dysfunction and pericarditis, prevents early heart failure and pulmonary hypertension, but does not eliminate completely cardiac disease in patients with thalassemia major.
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2003
 
DOI   
PMID 
Evangelos Terpos, Josu de la Fuente, Richard Szydlo, Evdoxia Hatjiharissi, Nora Viniou, John Meletis, Xenophon Yataganas, John M Goldman, Amin Rahemtulla (2003)  Tartrate-resistant acid phosphatase isoform 5b: a novel serum marker for monitoring bone disease in multiple myeloma.   Int J Cancer 106: 3. 455-457 Sep  
Abstract: Tartrate-resistant acid phosphatase isoform-5b (TRACP-5b), a new marker reflecting osteoclast activity, and osteoprotegerin (OPG) were measured in 121 patients with multiple myeloma (MM) at diagnosis, and in 63 of them during pamidronate administration, to define their correlation with the extent of bone disease and disease activity in MM. Radiographic evaluation of the skeleton, measurement of other markers of bone remodelling, including N-terminal cross-linking telopeptide of type-I collagen (NTX), bone alkaline phosphatase and osteocalcin and of markers of disease activity (beta2-microglobulin, paraprotein, interleukin-6 (IL-6), were also performed. Levels of TRACP-5b were increased (p <.0001), while OPG was decreased in MM patients compared to controls (p <.01). TRACP-5b levels were associated with the radiographically assessed severity of bone disease (p <.0001) as well as with levels of NTX, IL-6 and beta2-microglobulin (p <.001, for each biochemical parameter, respectively). The combination of pamidronate with VAD-chemotherapy produced a reduction in TRACP-5b, NTX, IL-6, paraprotein and beta2-microglobulin levels from the 2nd month of treatment, with no effect on bone formation and OPG. A strong correlation was observed between changes in TRACP-5b and changes in NTX, IL-6 and beta2-microglobulin, while TRACP-5b predicted the disease progression in 5 patients. These findings suggest that TRACP-5b is increased in MM, reflects the extent of myeloma bone disease and may have a predictive value. TRACP-5b has also proved to be very useful for monitoring antimyeloma treatment, which had no effect on OPG levels.
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PMID 
Evangelos Terpos, Nora Viniou, Josu de la Fuente, John Meletis, Ersi Voskaridou, Christos Karkantaris, George Vaiopoulos, John Palermos, Xenophon Yataganas, John M Goldman, Amin Rahemtulla (2003)  Pamidronate is superior to ibandronate in decreasing bone resorption, interleukin-6 and beta 2-microglobulin in multiple myeloma.   Eur J Haematol 70: 1. 34-42 Jan  
Abstract: OBJECTIVES: Bisphosphonates have been found to reduce skeletal events in patients with multiple myeloma (MM). This is the first randomised trial to compare the efficacy of pamidronate and ibandronate, a third-generation aminobisphosphonate, in bone turnover and disease activity in MM patients. METHODS: Patients with MM, stage II or III, were randomly assigned to receive either pamidronate 90 mg (group I: 23 patients) or ibandronate 4 mg (group II: 21 patients) as a monthly intravenous infusion in addition to conventional chemotherapy. Skeletal events, such as pathologic fractures, hypercalcaemia, and bone radiotherapy were analysed. Bone resorption markers [N-terminal cross-linking telopeptide of type-I collagen (NTX) and tartrate-resistant acid phosphatase type 5b (TRACP-5b)], bone formation markers (bone alkaline phosphatase and osteocalcin), markers of disease activity (paraprotein, CRP, beta 2-microglobulin), and interleukin-6 (IL-6) were also studied. RESULTS: In both groups, the combination of chemotherapy with either pamidronate or ibandronate produced a reduction in bone resorption and tumour burden as measured by NTX, IL-6, paraprotein, CRP, and beta 2-microglobulin from the second month of treatment, having no effect on bone formation. TRACP-5b also had a significant reduction in the pamidronate group from the second month of treatment and in the ibandronate group from the sixth month. However, there was a greater reduction of NTX, IL-6, and beta 2-microglobulin in group I than in group II, starting at the second month of treatment (P = 0.002, 0.001, and 0.004, respectively) and of TRACP-5b, starting at the fourth month (P = 0.014), that being continued throughout the 10-month follow-up of this study. There was no difference in skeletal events during this period. A significant correlation was observed between changes of NTX and changes of TRACP-5b, IL-6, and beta 2-microglobulin from the second month for patients of both groups. CONCLUSIONS: These results suggest that a monthly dose of 90 mg of pamidronate is more effective than 4 mg of ibandronate in reducing osteoclast activity, bone resorption, IL-6, and possibly tumour burden in MM. TRACP-5b has also proved to be a useful new marker for monitoring bisphosphonates treatment in MM.
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DOI   
PMID 
Evangelos Terpos, Richard Szydlo, Jane F Apperley, Evdoxia Hatjiharissi, Marianna Politou, John Meletis, Nora Viniou, Xenophon Yataganas, John M Goldman, Amin Rahemtulla (2003)  Soluble receptor activator of nuclear factor kappaB ligand-osteoprotegerin ratio predicts survival in multiple myeloma: proposal for a novel prognostic index.   Blood 102: 3. 1064-1069 Aug  
Abstract: Interaction between receptor activator of nuclear factor kappaB ligand (RANKL) and RANK/osteoprotegerin (OPG) plays a dominant role in osteoclast activation and possibly in plasma cell survival in multiple myeloma (MM). We measured soluble RANKL (sRANKL), OPG, and bone remodeling markers in 121 patients with newly diagnosed MM to evaluate their role in bone disease and survival. Serum levels of sRANKL were elevated in patients with MM and correlated with bone disease. The sRANKL/OPG ratio was also increased and correlated with markers of bone resorption, osteolytic lesions, and markers of disease activity. The sRANKL/OPG ratio, C-reactive protein (CRP), and beta2-microglobulin were the only independent prognostic factors predicting survival in multivariate analysis. We generated a prognostic index based on these factors that divided our patients into 3 risk groups. The low-risk group had a 96% probability of survival at 5 years, whereas the intermediate-risk and the high-risk groups had probabilities of survival of 52% and 0%, respectively. Not only do these results confirm for the first time in humans the importance of sRANKL/OPG in the development of bone disease, they also highlight the role of this pathway in the biology of plasma cell growth as reflected by its influence on survival.
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PMID 
Salem Akel, Despina Mavroyanni, Xenophon Yataganas, Evagelos Terpos, John Meletis, Kostas Anargyrou, Niki Stavrogianni, Gerasimos-Alexander Pangalis, Dimitris Loukopoulos, Nora Viniou (2003)  Clonal analysis of granulocyte-monocyte colony-forming unit cells with the human androgen receptor gene in chronic myeloid leukemia.   Int J Hematol 77: 5. 476-481 Jun  
Abstract: Coexistence of Philadelphia chromosome-negative (Ph-) progenitors with the Ph+ clone in the early chronic phase of chronic myeloid leukemia (CML) has been documented in previous reports. A different evaluation of methods is needed to justify the clonality of the residual Ph- progenitors. Therefore, the X chromosome inactivation patterns in individual granulocyte-monocyte colony-forming unit (CFU-GM) colonies were studied with the clonality assay for the human androgen receptor gene. A prerequisite for this evaluation was the validation of T-lymphocytes and buccal cells as control cells representing the constitutional lyonization. The percentages of polyclonal CFU-GM cells were determined in 9 Ph+ women with CML and in 5 healthy women. Results of the clonal analysis of CFU-GM colonies were compared with those from reverse transcriptase-polymerase chain reaction analysis of single colonies for BCR/ABL transcripts. Both methods of CFU-GM cell analysis were in agreement regarding the presence of variable proportions (0%-94%) of normal cells in CML. Our results suggest that (a) T-cells and buccal cells have potential for use as controls for the clonal analysis of CML cases and (b) this method can evaluate the frequency of polyclonal/clonal CFU-GM cells in CML cases and is applicable to the analysis of myeloid clonal disorders that lack specific molecular markers.
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PMID 
John Meletis, Evangelos Terpos (2003)  Recent insights into the pathophysiology of paroxysmal nocturnal hemoglobinuria.   Med Sci Monit 9: 7. RA161-RA172 Jul  
Abstract: Paroxysmal nocturnal hemoglobinuria (PNH) is a unique clonal stem cell disorder characterized by intravascular hemolysis, thrombotic events and bone marrow failure. There has been accelerated progress in understanding the mechanisms underlying the clinical features of the disease over the last decade. The development of PNH requires not only a somatic mutation of the phospatidylinositol glycan complementation class A (PIG-A) gene, but also a survival advantage of the PNH clone ('dual pathogenesis' theory). There is increasing evidence that negative selection against the non-mutated cells rather than positive selection of the PIG-A gene mutant cells is responsible for the dominance of the PNH clone. In this review, we summarize the important advances in the understanding of PNH, but we also concentrate on the presence of PNH clones in other hematological disorders, including aplastic anemia (AA), myelodysplastic syndromes (MDS), acute leukemias, and myeloproliferative and lymphoproliferative syndromes. The fuller comprehension of the pathophysiology of PNH may have wider implications than for PNH itself, as indicated by the presence of PNH clones in these hematological malignancies, and by the therapeutic implications of this fact, as already described in patients with AA and MDS.
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PMID 
Evangelos Terpos, Michalis Samarkos, Christos Meletis, Effie Apostolidou, Maria Tsironi, Konstantinos Korovesis, Despina Mavrogianni, Nora Viniou, John Meletis (2003)  Unusual association between increased bone resorption and presence of paroxysmal nocturnal hemoglobinuria phenotype in multiple myeloma.   Int J Hematol 78: 4. 344-348 Nov  
Abstract: Paroxysmal nocturnal hemoglobinuria (PNH) clones deficient in glycosylphosphatidylinositol-anchored molecules, including CD55 and CD59, have been previously described in patients with multiple myeloma (MM). The aim of this study was to investigate the possible association between existence of the PNH phenotype and myeloma bone disease. Forty-three patients with newly diagnosed MM were the subjects of the study. Radiographic evaluation of the skeleton was performed in all patients at diagnosis. The following biochemical markers were measured: bone resorption markers (tartrate-resistant acid phosphatase isoform 5b [TRACP-5b]and N-terminal cross-linking telopeptide of type-I collagen [NTX]), bone formation markers (bone alkaline phosphatase [bALP] and osteocalcin [OC]), osteoprotegerin (OPG), soluble receptor activator of nuclear factor KB ligand (sRANKL), and interleukin 6 (IL-6). Detection of CD55- and/or CD59-deficient red cell populations was performed after diagnosis. Patients with MM had elevated mean baseline NTX, TRACP-5b, sRANKL, and IL-6 levels compared with controls, whereas the mean values of bALP, OC, and OPG were significantly decreased. Four patients had no osteolytic lesions, whereas 8 patients had 1 to 3 lytic lesions, and 31 patients had more than 3 lytic lesions and/or pathologic fractures in the skeletal survey. CD55- and/or CD59-deficient red cell populations were observed in 56% of patients with MM. There was a strong correlation between the presence of PNH-like erythrocytes and increased bone resorption, as measured by NTX, TRACP-5b, and sRANKL/OPG ratio (P < .03, P < .02, and P < .02, respectively). There was also a significant correlation between PNH phenotype and severe bone disease (P < .02). These results suggest that there is a possible link between PNH phenotype and increased osteoclastic activity in MM owing to a potential effect of myeloma microenvironment on a preexisting PNH clone. Further studies are required for clarifying this phenomenon and investigating possible mechanisms of this unusual association.
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PMID 
K Anargyrou, G Paterakis, D Boutsis, M Politou, S I Papadhimitriou, M Siakandaris, J Vassiliadis, A Androulakis, J Meletis, J Rombos, A Tassiopoulou, G Vaiopoulos (2003)  An unusual case of CD4+ CD7+ CD56+ acute leukemia with overlapping features of type 2 dendritic cell (DC2) and myeloid/NK cell precursor acute leukemia.   Eur J Haematol 71: 4. 294-298 Oct  
Abstract: Type 2 dendritic cell (DC2) acute leukemia has been recently described. We report here an unusual case of a 17-yr-old adolescent with overlapping features of DC2 and myeloid/NK cell precursor acute leukemia as defined by Suzuki et al. The patient presented with lymphadenopathy and hepatosplenomegaly without extranodal manifestations in skin or elsewhere. The morphologic, cytochemical and immunophenotypic features were compatible with those described in DC2 acute leukemia, with co-expression of CD4, CD56 and CD123 antigens. The novel markers BDCA-4 and BDCA-2 considered specific for DC2s were co-expressed. However, bright CD7 positivity along with a dim expression of CD33 (57%) and CD117 (27%) were also noted. Additionally, there was bright expression of NG2 monoclonal antibody 7.1, a frequent finding in myeloid/NK cell precursor acute leukemia. The interpretation of the immunophenotypic profile leads to the hypothesis on the existence of borderline cases between DC2 and myeloid/NK cell precursor acute leukemia. Still, other hypotheses can not be overlooked, such as the possibility for a kind of variant monoblastic leukemia or of another rare entity of acute unclassified leukemia.
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2002
 
PMID 
Kostas Konstantopoulos, Emmanouel Agapitos, Veroniki Komninaka, Vasso Kritsova, John Meletis, Emmanouel Delaveris, Dimitris Loukopoulos (2002)  Acute Aspergillosis gastritis in a case of fatal aplastic anemia.   Scand J Infect Dis 34: 2. 148-149  
Abstract: A rare case of stomach perforation following acute aspergillosis gastritis in the course of a fatal severe aplastic anemia is reported.
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PMID 
Apostolia Maria Tsimberidou, George Paterakis, George Androutsos, Nikolaos Anagnostopoulos, Athanasios Galanopoulos, Themistoklis Kalmantis, John Meletis, Yiannis Rombos, Alexandros Sagriotis, Argyrios Symeonidis, Maria Tiniakou, Nikolaos Zoumbos, Xenophon Yataganas (2002)  Evaluation of the clinical relevance of the expression and function of P-glycoprotein, multidrug resistance protein and lung resistance protein in patients with primary acute myelogenous leukemia.   Leuk Res 26: 2. 143-154 Feb  
Abstract: The multidrug resistance (MDR) transporter-proteins P-glycoprotein (Pgp), multidrug resistance protein (MRP) and lung resistance protein (LRP) have been associated with treatment failure. The aim of this study was to investigate prospectively the clinical significance of expression and function of the MDR proteins, considering other prognostic factors, such as age, immunophenotype, and cytogenetics. Mononuclear cells of peripheral blood or bone marrow from 61 patients with de novo acute myelogenous leukemia (AML) were analyzed. The monoclonal antibodies JSB1, MRPm6 and LRP56 were used for expression studies. Accumulation and retention studies were performed using the substrates Daunorubicin, Calcein-AM, Rhodamine-123 and DiOC(2) in the presence or absence of the modifiers Verapamil, Genistein, Probenecid, BIBW22S and PSC833. Induction treatment consisted of a 3+7 combination of Ida/Ara-C for patients < or = 60 years of age and a 3+5 Ida/VP-16 combination per OS for patients >60. MDR function was expressed as the ratio of mean fluorescence intensity substrate in the presence of modifier over the substrate alone (resistance index, RI). Patients with advanced age, low CD15 expression and high RI for accumulation of DiOC(2) in the presence of BIBW22S had significantly lower complete remission (CR) rates. No factor was prognostic for event-free survival analysis, which was limited to remitters only. Overall survival was shorter in patients with advanced age, poor prognosis cytogenetics, high CD7 expression, and high RI for Daunorubicin efflux modulated by Verapamil. These results suggest that MDR transporter-proteins have a limited role in the treatment failure of patients treated with Idarubicin-based regimens.
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PMID 
John Meletis, Evangelos Terpos, Michalis Samarkos, Christos Meletis, Effie Apostolidou, Veroniki Komninaka, Konstantinos Korovesis, Konstantinos Anargyrou, Olga Benopoulou, Despina Mavrogianni, Eleni Variami, Nora Viniou, Konstantinos Konstantopoulos (2002)  Detection of CD55- and/or CD59-deficient red cell populations in patients with plasma cell dyscrasias.   Int J Hematol 75: 1. 40-44 Jan  
Abstract: Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal disorder characterized by a decrease or absence of glycosylphosphatidylinositol (GPI)-anchored molecules such as CD55 and CD59 from the surface of affected cells, resulting in intravascular hemolysis, cytopenia, and venous thrombosis. A PNH-like phenotype has been detected in various hematological disorders, mainly in aplastic anemia and myelodysplastic syndromes, but also in lymphoproliferative syndromes (LPSs). To the best of our knowledge, CD55- or CD59-deficient red cells have not been detected in plasma cell dyscrasias (PCDs). The aim of this study was the detection of CD55- and/or CD59-deficient red cell populations in patients with PCD. Seventy-seven patients were evaluated; 62 with multiple myeloma (MM), 7 with Waldenstrom macroglobulinemia (WM), 6 with monoclonal gammopathy of undetermined significance (MGUS), and 2 with heavy chain disease (HCD). The sephacryl gel microtyping system was applied; Ham and sucrose lysis tests were also performed on all samples with CD55- or CD59-negative populations. Red cells deficient in both molecules were detected in 10 (12.9%) of 77 patients with PCD: 2 (28.6%) of 7 with WM, 1 (16.6%) of 6 with MGUS, 6 (9.6%) of 62 with MM, and 1 of 2 patients with HCD. Isolated CD55 deficiency was found in 28.5% of all PCD patients, whereas isolated CD59 deficiency was not observed in any patients. These findings illustrate the existence of the PNH phenotype in the red cells of patients with PCD; further investigation is needed into the mechanisms and significance of this phenotype.
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PMID 
Despina Mavrogianni, Nora Viniou, Evi Michali, Evangelos Terpos, John Meletis, George Vaiopoulos, Marina Madzourani, Gerasimos Pangalis, Xenophon Yataganas, Dimitris Loukopoulos (2002)  Leukemogenic risk of hydroxyurea therapy as a single agent in polycythemia vera and essential thrombocythemia: N- and K-ras mutations and microsatellite instability in chromosomes 5 and 7 in 69 patients.   Int J Hematol 75: 4. 394-400 May  
Abstract: Polycythemia vera (PV) and essential thrombocythemia (ET) are chronic myeloproliferative diseases that carry intrinsically the potential for leukemic transformation. The aims of this study were (1) to detect involvement of N- and K-ras mutations in codons 12 and 13 in the pathogenesis of the chronic and blastic phases of PV and ET, (2) to study the occurrence of microsatellite instability (MSI) in chromosomes 5 and 7 during the chronic phase and blastic transformation of the disease, and (3) to examine the incidence of leukemia in patients treated with hydroxyurea (HU). Samples of PV and ET patients were analyzed with a polymerase chain reaction. No N- or K-ras mutations were detected. A positive score for MSI in chromosome 7 was found in 1 patient with PV during leukemic transformation. Three of 69 patients developed acute myelogenous leukemia, 2 with PV and 1 with ET. As of this report, the overall incidence of leukemic transformation is 5.7% (2/35 patients) in PV and 3.3% (1/30 patients) in ET patients treated with HU. These results indicate that (1) MSI is a genetic marker that can be detected, even in a small group of patients, at the blastic phase of the disease and (2) no increased leukemogenicity was noted in this group of patients treated with HU.
Notes:
 
PMID 
K Konstantopoulos, A Papadogianni, M Dimopoulou, C Kourelis, J Meletis (2002)  Pityriasis rosea associated with imatinib (STI571, Gleevec).   Dermatology 205: 2. 172-173  
Abstract: A tyrosine kinase inhibitor (STI571, Gleevec) has recently been applied in the treatment of chronic myeloid leukemia. We present the first reported case of pityriasis rosea occurring as a reaction to Gleevec in a woman with blast crisis of this disorder. It is suggested that although coincidental, this exanthem may be due to this agent.
Notes:
 
PMID 
Konstantinos Anargyrou, George Vaiopoulos, Evangelos Terpos, Maria Tsironi, Konstantinos Konstantopoulos, Michael Samarkos, John Meletis (2002)  Low dose melphalan is a treatment option in elderly patients with high risk myelodysplastic syndrome or secondary acute myeloblastic leukaemia.   Haematologia (Budap) 32: 2. 169-173  
Abstract: We present the case of a 71 year-old man with secondary acute myeloblastic leukemia, who was successfully treated with low dose melphalan plus Epo plus G-CSF. We treated the patient with 2 mg of melphalan once a day orally, G-CSF 5 mg/kg 3 times a week and Epo 10.000 ui subcutaneously 3 times a week until the maximum response was obtained. Complete remission was achieved after 16 weeks of continuous treatment. Treatment-related toxicity was not significant. We recommend the use of low dose melphalan in elderly patients with high risk MDS as a treatment option.
Notes:
 
DOI   
PMID 
John Meletis, Evangelos Terpos, Michalis Samarkos, Christos Meletis, Effie Apostolidou, Veroniki Komninaka, Konstantinos Anargyrou, Konstantinos Korovesis, Despina Mavrogianni, Eleni Variami, Nora Viniou, Konstantinos Konstantopoulos (2002)  Red cells with paroxysmal nocturnal hemoglobinuria-phenotype in patients with acute leukemia.   Hematology 7: 2. 69-74 Apr  
Abstract: CD55 and CD59 are complement regulatory proteins that are linked to the cell membrane via a glycosyl-phosphatidylinositol anchor. They are reduced mainly in paroxysmal nocturnal hemoglobinuria (PNH) and in other hematological disorders. However, there are very few reports in the literature concerning their expression in patients with acute leukemias (AL). We studied the CD55 and CD59 expression in 88 newly diagnosed patients with AL [65 with acute non-lymphoblastic leukemia (ANLL) and 23 with acute lymphoblastic leukemia (ALL)] using the sephacryl gel test, the Ham and sucrose lysis tests and we compared the results with patients' clinical data and disease course. Eight patients with PNH were also studied as controls. Red cell populations deficient in both CD55 and CD59 were detected in 23% of ANLL patients (especially of M(0), M(2) and M(6) FAB subtypes), 13% of ALL and in all PNH patients. CD55-deficient erythrocytes were found in 6 ANLL patients while the expression of CD59 was decreased in only 3 patients with ANLL. No ALL patient had an isolated deficiency of these antigens. There was no correlation between the existence of CD55 and/or CD59 deficiency and the percentage of bone marrow infiltration, karyotype or response to treatment. However no patient with M(3), M(5), M(7) subtype of ANLL and mature B- or T-cell ALL showed a reduced expression of both antigens. The deficient populations showed no alteration after chemotherapy treatment or during disease course. This study provides evidence about the lower expression of CD55 and CD59 in some AL patients and the correlation with their clinical data. The possible mechanisms and the significance of this phenotype are discussed.
Notes:
 
PMID 
Evangelos Terpos, Athina Mougiou, Alexandra Kouraklis, Aria Chatzivassili, Evridiki Michalis, Nicholas Giannakoulas, Eleni Manioudaki, Anna Lazaridou, Vassiliki Bakaloudi, Maria Protopappa, Dimitra Liapi, Elisavet Grouzi, Agapi Parharidou, Argyris Symeonidis, Garoufalia Kokkini, Nikolaos P Laoutaris, George Vaipoulos, Nikolaos I Anagnostopoulos, John I Christakis, John Meletis, Konstantinos L Bourantas, Nicholas C Zoumbos, Xenophon Yataganas, Nora-Athina Viniou (2002)  Prolonged administration of erythropoietin increases erythroid response rate in myelodysplastic syndromes: a phase II trial in 281 patients.   Br J Haematol 118: 1. 174-180 Jul  
Abstract: Treatment with recombinant human erythropoietin (rHuEpo) improves anaemia in approximately 20% of patients with myelodysplastic syndromes (MDS). We investigated the potential advantage of a prolonged administration of rHuEpo to achieve higher erythroid response rates (RR) in 281 MDS patients: 118 with refractory anaemia (RA), 77 with refractory anaemia and ringed sideroblasts (RARS), 59 with refractory anaemia with excess of blasts and blast count < 10% (RAEB-I), and 27 with RAEB and blast count between 11-20% (RAEB-II). rHuEpo was given subcutaneously at a dose of 150 U/kg thrice weekly, for a minimum of 26 weeks. Response to treatment was evaluated after 12 and 26 weeks of therapy. The overall RR was 45.1%; the RR for RA, RARS, RAEB-I and RAEB-II were 48.3%, 58.4%, 33.8% and 13% respectively. A significant increase in RR was observed at week 26 in RA, RARS and RAEB-I patients, as the response probability increased with treatment duration. The RR was higher in the good cytogenetic prognostic group and serum Epo level of > 150 U/l at baseline predicted for non-response. The median duration of response was 68 weeks and the overall risk of leukaemic transformation was 21.7%. These results suggest that prolonged administration of rHuEpo produces high and long-lasting erythroid RR in MDS patients with low blast counts, particularly in those with pretreatment serum Epo levels of < 150 U/l and good cytogenetic prognosis.
Notes:
2001
 
PMID 
J Meletis, E Terpos, M Samarkos, C Meletis, K Konstantopoulos, V Komninaka, E Apostolidou, O Benopoulou, K Korovesis, D Mavrogianni, E Variami, X Yataganas, D Loukopoulos (2001)  Detection of CD55 and/or CD59 deficient red cell populations in patients with aplastic anaemia, myelodysplastic syndromes and myeloproliferative disorders.   Haematologia (Budap) 31: 1. 7-16  
Abstract: Paroxysmal nocturnal haemoglobinuria (PNH) is an acquired clonal stem cell disorder characterized by intravascular haemolysis, venous thrombosis, marrow hypoplasia, frequent episodes of infection, and rarely leukaemic conversion. At the cellular level, PNH is characterized by the decrease or absence of glycosylphosphatidylinositol (GPI)-anchored molecules, such as CD55 and CD59, from the cell surface. PNH-like clones have been described in various haematological disorders. The link between PNH and aplastic anaemia (AA) has been established but the relationship of PNH with myelodysplastic syndromes (MDS) or myeloproliferative disorders (MPD) remains unclear. In this study, the presence of CD55 and/or CD59 defective (PNH-like) red cell populations was evaluated in 21 patients with AA, 133 with MDS, 197 with MPD, 7 with PNH and in 121 healthy blood donors using the Sephacryl Gel Test microtyping system. Red cell populations deficient in both molecules CD55 and CD59 were detected in 33.3% of AA patients, in 16.5% of MDS patients (50% with hypoplastic bone marrow), in 14.2% of MPD patients (more often in essential thrombocythemia, 21.2%) and in all PNH patients. CD55 deficient red cell populations were found in 14.2% of patients with AA, 12.7% of patients with MDS and 21.3% of patients with MPD. CD59 deficient populations were found in 9.5% of AA patients, 2.2% of MDS patients and 2% of MPD patients. These results indicate an association between PNH, AA and MDS or even between PNH and MPD. Further investigation is necessary to work out the mechanisms of this association, and to define classification criteria for borderline cases, where diagnosis is difficult.
Notes:
 
PMID 
S Tassiopoulos, K Konstantopoulos, K Korovesis, J Meletis, A Andreopoulos, K Chatzikonstantinou, A Aessopos (2001)  Multilocalized pyomyositis in a previously healthy subject.   Scand J Infect Dis 33: 11. 857-858  
Abstract: A case of pyomyositis is presented. This case is unique in the literature as at least 29 abscesses were detected, affecting the vast majority of big muscle groups. We outline the origin of this disease entity which selectively affects striated muscles. We also discuss its natural history and management strategy.
Notes:
 
PMID 
E Terpos, J Palermos, N Viniou, G Vaiopoulos, J Meletis, X Yataganas (2001)  Pamidronate increases markers of bone formation in patients with multiple myeloma in plateau phase under interferon-alpha treatment.   Calcif Tissue Int 68: 5. 285-290 May  
Abstract: Bisphosphonates are potent inhibitors of osteoclastic activity and reduce the disease-related skeletal complications when they are used in combination with chemotherapy in patients with multiple myeloma (MM). Pamidronate also inhibits apoptosis of primary osteoblastic cells and probably induces apoptosis on human MM cells and osteoclasts. It has been reported that interferon-alpha (IFN-alpha) decreases bone resorption and that low doses of IFN-alpha result in a significant increase in serum osteocalcin (OSC). The aim of this study was to determine the effects of pamidronate treatment on biochemical markers of bone resorption [cross-linked N-telopeptides of type I collagen (NTx)], bone formation [bone alkaline phosphatase (BAP) and OSC], disease activity [beta2-microglobulin, CRP, paraprotein], and interleukin-6 (IL-6) in patients with MM in plateau phase under IFN-alpha maintenance. The above parameters were evaluated in 28 patients (13 M, 15 F, median age 70 years) during maintenance treatment, before the addition of pamidronate and after 1, 3, 6, 9, 12, and 14 months of the combined therapy. The addition of pamidronate to maintenance treatment resulted in a significant reduction of NTx, IL-6, beta2-microglobulin, CRP from the 3rd month and paraprotein from the 6th month of treatment, whereas BAP and OSC were significantly increased from the 6th month. These changes continued during the 14-month follow-up of the combined treatment. Multivariate analysis showed a significant negative correlation between changes of BAP and OSC and the patients' age. The greater increase of the bone formation markers was observed in younger patients. These results suggest that, in addition to the inhibition of osteoclastic activity, pamidronate in combination with IFN-alpha was shown to induce bone formation in patients with MM in the plateau phase.
Notes:
 
DOI   
PMID 
J Meletis, E Terpos, M Samarkos, C Meletis, E Apostolidou, V Komninaka, K Korovesis, D Mavrogianni, D Boutsis, E Variami, N Viniou, K Konstantopoulos, D Loukopoulos (2001)  Detection of CD55- and/or CD59-deficient red cell populations in patients with lymphoproliferative syndromes.   Hematol J 2: 1. 33-37  
Abstract: INTRODUCTION: Paroxysmal nocturnal hemoglobinuria is an acquired clonal stem cell disorder characterized by the decrease or absence of glycosylphosphatidylinositol-anchored molecules from the surface of the affected cells, such as CD55 and CD59, resulting in chronic intravascular hemolysis, cytopenia and increased tendency to thrombosis. PNH-phenotype has been described in various hematological disorders, mainly in aplastic anemia and myelodysplastic syndromes, while it has been reported that complete deficiency of CD55 and CD59 has also been found in patients with lymphoproliferative syndromes, like non-Hodgkin's lymphomas. MATERIALS AND METHODS: The presence of CD55- and/or CD59-defective red cell populations was evaluated in 217 patients with lymphoproliferative syndromes. The study population included 87 patients with NHL, 55 with HD, 49 with CLL, 22 with ALL and four with hairy cell leukemia. One hundred and twenty-one healthy blood donors and seven patients with PNH were also studied as control groups. The sephacryl gel microtyping system was performed for the detection of CD55- and CD59-deficient red cell populations. Ham and sucrose lysis tests were also performed in all samples with CD55 or CD59 negative populations. RESULTS: Red cell populations deficient in both CD55 and CD59 molecules were detected in 9.2% of patients with lymphoproliferative syndromes (more often in ALL and nodular sclerosis type of HD) and in all PNH patients. CD55-deficient red cell populations were found in 8.7% of LPS patients (especially in low grade B-cell NHL), while CD59-deficient populations were found in only two patients with low grade B-cell NHL. CONCLUSION: These data indicate a possible association between paroxysmal nocturnal hemoglobinuria phenotype and lymphoproliferative syndromes, while further investigation is necessary to work out the mechanisms and the significance of the existence of this phenotype in these patients.
Notes:
2000
 
PMID 
N Stavroyianni, X Yataganas, D Abazis, C Pangalos, J Meletis (2000)  Acute promyelocytic leukemia relapsing into FAB-M2 acute myeloid leukemia with trisomy 8.   Cancer Genet Cytogenet 117: 1. 82-83 Feb  
Abstract: Acute promyelocytic leukemia was diagnosed in a 48-year-old man; the karyotype was normal, whereas reverse transcriptase polymerase chain reaction (RT-PCR) analysis identified PML/RAR alpha chimeric transcripts of the bcr3 type. Rather unexpectedly, the patient did not respond to alltrans retinoic acid administration; he attained complete remission with conventional chemotherapy and became PML/RAR alpha negative. Two years later, while PML/RAR alpha negative on RT-PCR, he presented with thrombocytopenia. Bone marrow examination was compatible with myelodysplasia of the RAEB type; the karyotype was normal. Then, after 10 months, he developed overt acute myeloid leukemia with PML/RAR alpha negative, French-American-British M2 blasts; karyotypic analysis revealed mosaicism for trisomy 8.
Notes:
 
PMID 
E Terpos, M K Angelopoulou, E Variami, J C Meletis, G Vaiopoulos (2000)  Sjögren's syndrome associated with multiple myeloma.   Ann Hematol 79: 8. 449-451 Aug  
Abstract: Sjögren's syndrome (SS) is a chronic autoimmune disease of unknown etiology characterized by lymphocytic infiltration of the exocrine glands and a polyclonal B-cell activation; it is demonstrated by the presence of multiple autoantibodies against organ- and non-organ-specific autoantigens. SS is associated with malignant lymphomas, Waldenstrom's macroglobulinemia and benign monoclonal gammopathy, while its relationship with multiple myeloma is extremely rare. The association between multiple myeloma and rheumatoid arthritis and other autoimmune diseases has been established, but it is not clear why a B-cell proliferation like myeloma occurs more rarely than other B-cell disorders in patients with SS. We describe a patient who presented with multiple myeloma and SS that might have existed for at least 2 years prior to the appearance of myeloma.
Notes:
 
PMID 
E Terpos, J Palermos, K Tsionos, K Anargyrou, N Viniou, P Papassavas, J Meletis, X Yataganas (2000)  Effect of pamidronate administration on markers of bone turnover and disease activity in multiple myeloma.   Eur J Haematol 65: 5. 331-336 Nov  
Abstract: AIM: Bisphosphonates are potent inhibitors of osteoclastic activity and are used in the treatment of multiple myeloma (MM) in combination with chemotherapy. The effect of pamidronate on markers of bone resorption [cross-linked N-telopeptides of type I collagen (NTx)], markers of bone formation [serum alkaline phosphatase (BAP) and osteocalcin (OSC)], interleukin-6 (IL-6), beta2-microglobulin, CRP, paraprotein and disease-related pain and skeletal events has been evaluated in 62 newly diagnosed patients with MM. PATIENTS AND METHODS: The patients were randomly assigned to two groups: the first included 32 patients under chemotherapy and pamidronate (group I) and the second 30 patients on chemotherapy only (group II). Pamidronate was administered at a monthly dose of 90 mg iv, and the above parameters were evaluated at the beginning of this study and after 1, 3, 6, 9, 12 and 14 months of treatment. RESULTS: The addition of pamidronate to chemotherapy resulted in a significant reduction of NTx, IL-6 and paraprotein from the 3rd month and of beta2-microglobulin, CRP and pain from the 6th month of treatment. No changes of NTx, IL-6, beta2-microglobulin, CRP or skeletal events were observed in patients of group II, while paraprotein was significantly reduced after 6 months of treatment. The differences in NTx, IL-6, paraprotein and beta2-microglobulin were statistically significant between the two groups. Multivariate analysis revealed a significant correlation between changes of NTx, changes of IL-6 in both groups and reduction of pain and paraprotein in group I. CONCLUSIONS: These results suggest that pamidronate may have a synergistic action with chemotherapy in decreasing osteoclastic activity, in reducing markers of myeloma activity and myeloma related pain and in improving the quality of life in patients with MM.
Notes:
1999
 
PMID 
E Plata, N Viniou, D Abazis, K Konstantopoulos, C Troungos, G Vaiopoulos, J Meletis, C Kittas, C Pangalos, X Yataganas (1999)  Cytogenetic analysis and RAS mutations in primary myelodysplastic syndromes.   Cancer Genet Cytogenet 111: 2. 124-129 Jun  
Abstract: Cytogenetic analysis was performed in 60 patients with primary myelodysplastic syndromes--diagnosed, treated, and followed in our department. In 41 cases, the presence of the NRAS mutation was also evaluated. The aim of this study was to evaluate the prognostic value of chromosomal abnormalities and NRAS mutation. The median age of the patients was 67 years (18-88 years), and the French-American-British classification was as follows: refractory anemia 26, refractory anemia with ring sideroblasts 4, refractory anemia with excess of blast cells 15, refractory anemia with excess of blast cells in transformation 3, and chronic myelomonocytic leukemia 12. Survival analysis was performed for the patients with a normal (n = 35), an abnormal (n = 25) karyotype and with a single (n = 15) or multiple (n = 10) cytogenetic abnormalities. Abnormal karyotypes were detected in 25 of the 60 patients (41.6%). Fifteen of these patients had a single and 10 had two or more lesions. The median survival of the patients with a normal (33.1 months) and with an abnormal (36.5 months) karyotype was not significantly different. Patients with multiple lesions had a reduced median survival compared with patients with single anomalies (19.2 versus 39.7 months, p = 0.5). Patients with an abnormal karyotype progressed to acute leukemia more frequently compared with patients without lesions (36 versus 28.6%, p = 0.5). NRAS mutation was detected in 2 of 10 CMMoL patients studied and in none of the 31 patients with other types of myelodysplastic syndrome. Marrow blasts more than 10% significantly affected survival.
Notes:
 
PMID 
E Variami, E Terpos, S Vgenopoulou, G Kanellopoulou, J Meletis (1999)  Inflammatory pseudotumor of the spleen: a case report and review of the literature.   Ann Hematol 78: 12. 560-563 Dec  
Abstract: Inflammatory pseudotumor of the spleen is a benign tumorous lesion of unknown etiology and pathogenesis that has been described in only a few cases in the literature. Recognition of this rare entity is important, as the clinical manifestations and imaging features could be indistinguishable from a lymphoproliferative disorder or another malignancy of the spleen. We report a new case and review the clinical presentation, laboratory findings, pathological and immunohistochemical studies, treatment, and prognosis of the previously reported cases of inflammatory pseudotumor of the spleen.
Notes:
1998
 
PMID 
J Meletis, M Samarkos, S Mesogitis, C Meletis, A Mougiou, E Terpos, A Tsimberidou, A Andreopoulos, K Konstantopoulos, D Loukopoulos (1998)  Severe aplastic anaemia relapsing during a pregnancy; spontaneous remission following termination.   Haematologia (Budap) 29: 2. 147-151  
Abstract: The case of a 29-year-old woman with aplastic anaemia in remission who relapsed during pregnancy is reported here. Following successful Caesarean delivery, spontaneous remission was obtained and the patient remains well thereafter. Pathogenetic and therapeutic aspects of this rare complication of pregnancy are discussed.
Notes:
 
PMID 
K Konstantopoulos, E Terpos, H Prinolakis, A Kanta, E Variami, G Kanellopoulou, G Vaiopoulos, A Floros, A Androulaki, J Meletis (1998)  Systemic lupus erythematosus presenting as myelofibrosis.   Haematologia (Budap) 29: 2. 153-156  
Abstract: Myelofibrosis is not frequent in systemic lupus erythematosus (SLE). A review in the literature reveals that the co-incidence is rather rare since there are only a few papers reporting this combination. The female patient described hereby, presented with thrombocytopenia; following investigation, the diagnosis of SLE was established and bone marrow examination revealed an increase of marrow reticulin. Treatment with steroids reversed both thrombocytopenia and bone marrow fibrosis.
Notes:
1997
 
PMID 
J Meletis, E Michali, M Samarkos, K Konstantopoulos, C Meletis, E Terpos, A Tsimberidou, E Chandrinou, N Viniou, Y Rombos, G A Pangalis, X Yataganas, D Loukopoulos (1997)  Detection of "PNH red cell" populations in hematological disorders using the Sephacryl Gel Test micro typing system.   Leuk Lymphoma 28: 1-2. 177-182 Dec  
Abstract: Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal disorder characterised by an unusual sensitivity of abnormal red cell population(s) to complement lysis, due to a complete or incomplete defect of various surface molecules, including CD55 and CD59. PNH has been associated with various hematological disorders. Using a newly introduced method, the Sephacryl gel test microtyping system, we investigated the presence of CD55 or CD59 defective red cell populations in several hematological disorders. It was also found that a large proportion of such patients possess CD55 deficient populations, while a smaller but still significant proportion possess CD59 deficient populations. Defective red cell populations were detected in normal subjects as well. These findings need further investigation. Nevertheless the Sephacryl Gel Test microtyping system although non specific, seems to be useful in screening for the PNH and/or "PNH-like" red cell defect in several hematological disorders.
Notes:
 
PMID 
N Viniou, E Michali, J Meletis, A Andreopoulos, G Vaiopoulos, N Stavroyianni, D Loukopoulos, X Yataganas (1997)  Trisomy 8 in a patient who responded to therapy with all-trans-retinoic acid and developed paroxysmal nocturnal haemoglobinuria.   Br J Haematol 97: 1. 135-136 Apr  
Abstract: Trisomy 8 is the most common numerical chromosomal abnormality in myelodysplastic syndromes (MDS). Paroxysmal nocturnal haemoglobinuria (PNH) is an aquired haemolytic anaemia, clonal in nature, due to somatic mutation. PNH may evolve to aplastic anaemia, to MDS or to acute myeloid leukaemia. We present a patient who had trisomy 8 mosaicism at disease presentation who received therapy with all-trans-retinoic acid, responded to therapy, and developed PNH in the course of the disease. Cytogenetics at the time of PNH diagnosis showed a normal karyotype.
Notes:
1996
 
PMID 
J Meletis, M Samarkos, D Abazis, E Michali, S Vavourakis, E Plata, J Rombos, K Konstantopoulos, K Pangalos, X Yataganas, D Loukopoulos (1996)  Trisomy 11 with loss of the Y chromosome and trisomy 13 in a case of de novo acute myeloid leukemia.   Cancer Genet Cytogenet 86: 1. 65-68 Jan  
Abstract: We report a man with de novo acute myeloid leukemia (M4 of the FAB classification) bearing two abnormal clones in the bone marrow cells. The clones showed trisomy 11 with loss of the Y chromosome and trisomy 13, respectively.
Notes:
 
PMID 
G Vaiopoulos, N Viniou, E Plata, K Konstantopoulos, A Andreopoulos, Y Rombos, J Meletis, D Loukopoulos, X Yataganas (1996)  Development of plasma cell tumors during treatment of multiple myeloma.   Ann Hematol 72: 5. 317-320 May  
Abstract: Plasma cell tumors (plasmacytomas-PCT) of the bone, or extramedullary PCT, may be diagnosed in patients with or without the diagnostic criteria for systemic multiple myeloma (MM). The reason for the local development of these tumors is not clear. Recent reports emphasize the contribution of CT and MRI in the detection of bone lesions and their expansion into the soft tissues. We report the development of PCT in nine patients with MM under maintenance treatment with alpha-IFN, of whom six had no evidence of systemic relapse and three had indications of early relapse. The PCT were located in the pelvis (4), thoracic (3), cervical (1), and lumbar (2) spine and in 8/9 cases were not demonstrable on plain X-rays. These observations suggest that frequent screening with advanced imaging techniques may detect local disease expansion in asymptomatic patients. Early application of radiochemotherapy may improve prognosis.
Notes:
1995
 
PMID 
N A Viniou, X Yataganas, K Stamatopoulos, I Xefteri, T Kalmantis, P Papasavas, C Mitsulis, J Rombos, J Meletis, K Bourantas (1995)  Reverse transcription polymerase chain reaction for the diagnosis and molecular monitoring of the PML/RAR alpha fusion gene in acute promyelocytic leukemia.   Cancer Genet Cytogenet 84: 2. 91-94 Oct  
Abstract: Acute promyelocytic leukemia (APL) is characterized by a specific t(15;17) translocation and a high rate of response to all-trans retinoic acid. The translocation generates a PML/RAR alpha chimeric gene which is transcribed in a fusion PML/RAR alpha mRNA. In this study, by using RT-PCR, we examined 14 APL patients for PML/RAR alpha fusion gene transcripts. Eight patients were studied at diagnosis, 2 at relapse, 1 both at relapse and after reinduction, 1 both at diagnosis and after three cycles of consolidation chemotherapy, and 2 patients were examined for minimal residual disease (MRD) 4 months after completing treatment. A positive result was observed in all 14 cases. Two patients who were in complete hematologic remission had evidence of hematologic relapse soon after the positive test. We conclude that RT-PCR for APL yields important diagnostic and prognostic information for the APL patients.
Notes:
 
PMID 
J Meletis, M Samarkos, E Michali, S Vavourakis, C Meletis, C Poziopoulos, N Stavrogianni, K Konstantopoulos, G Vaiopoulos, X Yataganas (1995)  Correction of anaemia and thrombocytopenia in a case of adult type I osteopetrosis with recombinant human erythropoietin (rHuEPO).   Br J Haematol 89: 4. 911-913 Apr  
Abstract: A case of adult osteopetrosis Type I was diagnosed in a 22-year-old female. She presented for investigation of anaemia with 'myelophthisic' characteristics and extramedullary haemopoiesis which was resistant to haematinics, nandrolone and low-dose corticosteroids. She became progressively transfusion-dependent with gradually worsening thrombocytopenia. She was successfully treated with recombinant erythropoietin. Anaemia as well as thrombocytopenia were corrected. There appeared to be a synergistic action of erythropoietin with steroids.
Notes:
 
PMID 
G Vaiopoulos, K Konstantopoulos, C Kittas, A Hatzakis, K Bogdanos, A Mastrovassilopoulos, J Meletis, D Loukopoulos (1995)  Histological and functional changes in the salivary glands in thalassaemia major.   Haematologia (Budap) 27: 1. 33-38  
Abstract: Oral salivary secretion and oral histology in 15 multi-transfused adult thalassaemia homozygotes was studied. Iron stores of minor salivary glands were also histochemically determined. Salivary secretion in multi-transfused thalassaemia patients was subclinically decreased, but no clear correlation was evident between salivary secretion impairment and salivary gland destruction by iron deposition, lymphocyte infiltration and fibrosis. The underlying mechanism remains to be determined.
Notes:
 
PMID 
N A Viniou, M Matzourani, X Yataganas, J Meletis, G Pangalis, D Loukopoulos (1995)  Correlation of the site of M-bcr breakpoint with chronic phase duration, blastic crisis lineage and thrombocytosis in Ph1-positive chronic myelogenous leukemia.   Leuk Lymphoma 18: 3-4. 335-339 Jul  
Abstract: The breakpoints on chromosome 22 in CML occur within a 5.8 kb region called the Major breakpoint cluster region (M-bcr). DNA mapping within the M-bcr region was performed in 41 long term followed Ph1-positive CML patients using the Southern blot technique. The purpose of this study was to determine whether localization of M-bcr breakpoint correlates with the length of chronic phase of the disease, blastic crisis lineage and thrombocytosis at the time of initial diagnosis. Our results fail to indicate any correlation between breakpoint localization and duration of chronic phase, blastic crisis lineage and platelet count at diagnosis.
Notes:
1994
 
PMID 
J Meletis, S Papavasiliou, X Yataganas, S Vavourakis, K Konstantopoulos, C Poziopoulos, M Samarkos, E Michali, M Dalekou, G Eliopoulos (1994)  'Fetal' erythropoiesis following bone marrow transplantation as estimated by the number of F cells in the peripheral blood.   Bone Marrow Transplant 14: 5. 737-740 Nov  
Abstract: The aim of this study was to define factor(s) influencing fetal erythropoiesis following bone marrow transplantation. Thirty-one transplanted patients (14 males, 17 females) were studied. The underlying diseases were chronic myelogenous leukaemia (CML, 18 patients), acute myeloblastic leukaemia (AML, 7 patients) and acute lymphoblastic leukaemia (ALL, 6 patients). Reticulocyte and peripheral F cell estimation was carried out in donors and patients before transplantation and repeatedly during recovery. For F cell estimation, an indirect immunofluorescence assay was utilized. A significant increase above pre-BMT values in the percentage of F cells was observed in all patients from days 11 to 40 after transplantation. The increase of F cells on days 15, 18, 25, 32, 40 and 50 after transplantation was statistically significant in 14 patients who had shown an increase of F cells following chemotherapy (high responders) compared with the remaining 17 patients who did not respond so significantly. This finding supports the influence of the host bone marrow micro environment. The nature of the mechanisms operating remains to determined.
Notes:
1993
 
PMID 
J Meletis, S Vavourakis, T Andreopoulos, X Yataganas, C Poziopoulos, S Lafioniatis, K Konstantopoulos, D Loukopoulos (1993)  Recovery of carbimazole-induced agranulocytosis following recombinant granulocyte-macrophage colony stimulating factor (rhGM-CSF) administration.   Haematologica 78: 5. 329-331 Sep/Oct  
Abstract: A 56 year old female patient treated with carbimazole for hyperthyroidism developed agranulocytosis complicated by pneumonia. She was treated by sc administration of 6 micrograms/kg rhGM-CSF for 10 days. The first neutrophils appeared in the peripheral blood on the 4th day and normal numbers are reached on the 7th day of treatment. This was accompanied by a rapid resolution of fever. The use of growth factors may be justified in cases of drug-induced agranulocytosis.
Notes:
1991
 
PMID 
X Yataganas, Y Rombos, G Vayopoulos, J Meletis, A Avlami (1991)  Randomized clinical trial comparing ceftriaxone/amikacin versus ceftazidime/amikacin as initial therapy of febrile episodes in neutropenic patients.   Chemotherapy 37: 5. 376-381  
Abstract: Neutropenic patients with underlying hematologic (usually malignant) diseases were randomized to receive either 2 g ceftriaxone once daily +0.5 g amikacin or 2 g ceftazidime twice daily +0.5 g amikacin b.i.d. when fever was higher than 38 degrees C and granulocyte counts less than 0.5 x 10(9)/l. 25 patients were included in each treatment group. Successful outcome of treatment was observed in 28 (13/15) and in an additional 5 (2/3) patients after modification of the therapy. Tolerability was excellent in both groups.
Notes:
 
PMID 
X Yataganas, J Meletis, E Plata, N Viniou, F Deligiannis, C Tsekoura, E Voscaridou, V Boussiotis, J Rombos, G Vayopoulos (1991)  alpha Interferon treatment of essential thrombocythaemia and other myeloproliferative disorders with excessive thrombocytosis.   Eur J Cancer 27 Suppl 4: S69-S71  
Abstract: The effect of recombinant interferon alfa-2b on platelet count, thrombocytosis-associated symptoms and marrow fibrosis was studied in 18 patients with myeloproliferative diseases and associated thrombocytosis (nine with essential thrombocythaemia, three with polycythaemia vera, three with myelofibrosis and three with chronic myelogenous leukaemia). A reduction of the platelet count below 600 x 10(9)/L was achieved in 94%, and below 400 x 10(9)/L in 77% of the patients within 8 to 330 days of treatment. The selective thrombocytosis-reducing effect of alpha interferon was maintained for long periods of time in most patients without serious side effects. Thrombocytosis-associated symptoms were relieved once the number of platelets was reduced to near normal levels. Marrow reticulin content was found to be reduced after treatment in two of the seven patients studied. Side effects of alpha interferon were flu-like symptoms, which usually subsided within 7 days of treatment.
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PMID 
X Yataganas, G Eliopoulos, S Koulocheri, N Viniou, E Plata, P Panagiotidis, G Vayopoulos, J Meletis, P Fessas (1991)  The effect of recombinant alpha-interferon on natural killer cell activity and clinical course in patients with myelodysplastic syndrome.   Ann Hematol 62: 6. 225-229 Jun  
Abstract: Thirteen patients with myelodysplastic syndrome (MDS) were included in this study and consented to treatment with recombinant alpha-interferon (a-IFN). These patients were subclassified: six as RAEB, one as RAEB-T and six as CMML. T-cell subsets and natural killer cells were identified in the peripheral blood with the use of monoclonal antibodies and natural killer cell activity (NKa) was assayed before, during and after a-INF treatment. The treatment schedule consisted of 2.0 MU/m2 sc t.i.w. continuously for the three months. Prior to treatment, NKa was found decreased in 11 of 13 patients as compared to that of normal individuals. Following a-IFN administration, a rise of NKa was observed in eight of the eleven patients. In those who responded, a-IFN was continued for 1 to 21 months. Alpha-IFN treatment was myelosuppressive for most of the patients, but transient increase of the number of neutrophils and platelets was observed in 3 and of the reticulocytes in one patient. Disease progression was recorded in 9/13 patients (69%) at a median time of 17.3 months. The median overall survival was 30.5 months (range 7.5 to 65+ months). No evidence of a relationship was found between the rise in Nka and the limited clinical improvement observed. Two NKa responders under continuous a-IFN treatment are in stable clinical condition for 36+ and 65+ months. The study provides only limited evidence that a-IFN may improve the clinical course of patients with MDS.
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1990
 
PMID 
G Eliopoulos, J Meletis, P Fessas, N P Anagnou (1990)  Defective CSA-dependent granulopoiesis in patients with chronic drug-induced neutropenia.   Haematologia (Budap) 23: 2. 101-109  
Abstract: Colony stimulating activity (CSA) and granulocyte-macrophage progenitor cells (GM-CFC) were assayed in the bone marrow and peripheral blood of 17 patients with drug-induced chronic neutropenia. Leukocyte-derived and monocyte/macrophage-derived CSA from the neutropenic patients was found to be significantly decreased compared to normal control. However, bone marrow and peripheral blood GM-CFC were within normal limits. These data suggest that in neutropenic patients monocyte/macrophages exhibit most likely a qualitative defect in CSA production, which may account at least in part, for the impaired granulopoiesis observed in drug-induced neutropenia.
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1989
 
PMID 
J Meletis, X Yataganas, G Vayopoulos, K Konstantopoulos, D Kyriakou, F Deligiannis, P Fessas (1989)  Tropical pyomyositis in a Greek adult.   Scand J Infect Dis 21: 3. 343-344  
Abstract: A case of tropical pyomyositis in a 24-year-old Greek is reported. The patient presented with high fever and swelling of the left thigh, generalized lymphadenopathy and multiple infiltrations in both lung fields on X-ray of the chest. Multifocal muscle abscesses were detected by CT scan of the left thigh and gluteal area. Staphylococcus aureus was identified in cultures of the purulent material which was surgically drained. The patient was subsequently treated with appropriate antibiotics. Lack of familiarity with this disease caused diagnostic confusion and delayed the initiation of treatment.
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1988
 
PMID 
E Gluckman, M Cavazzana, A Devergie, J Meletis, G Arlet, Y Perol, M Boiron (1988)  Prevention of bacterial infections after bone marrow graft by broad-spectrum oral antibiotics, absorbable (pefloxacin, penicillin) and non absorbable (cephalosporin, gentamycin, bacitracin)   Pathol Biol (Paris) 36: 7. 902-906 Sep  
Abstract: In a consecutive series of 65 patients treated by allogeneic bone marrow transplantation, we have compared the efficacy on prevention of bacterial infection of total gut decontamination with oral non absorbable antibiotics or with oral absorbable broad spectrum antibiotics. On day-8, all patients were randomly allocated to one group: Group I received orally pefloxacin 400 mg/day and penicillin 3 M UI/day. Group II received capsules containing cephalothin 250 mg, gentamicin 20 mg and bacitracin 150 UI. Each patient received 9 to 12 capsules per day according to body weight. Patients less than 5 years old or with severe hepatic abnormalities were excluded from the study. All patients were treated in LAF room with usual precautions of asepsis. They received sterile food. In addition, they were on ketoconazole for prophylaxis of fungal infections and acyclovir for prevention of herpes infections. Antibiotics were started on day-8 before bone marrow transplantation and stopped 15 days after discharge from the hospital. 32 patients were allocated to Group I and 33 in Group II. There was no difference between both groups according to age, sex, diagnosis. After transplant, the one year survival and the complications were similar in both groups. The median time of decontamination was 65 days, the mean number of days of agranulocytosis was 20 days, the mean number of days of fever was 7 days in both groups. The compliance was better in Group I but the treatment had to be modified in 9 patients of Group I because of liver abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS)
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1987
 
PMID 
A Devergie, E Gluckman, F Varrin, J L Huret, J Meletis, H De Castro, D Bombail, E Vilmer, R Traineau, M Boiron (1987)  Allogenic bone marrow grafts in chronic myeloid leukemia   Nouv Rev Fr Hematol 29: 1. 69-72  
Abstract: Between August 1979 and April 1986, we treated 70 patients with chronic myeloid leukemia by supralethal chemoradiotherapy followed by bone marrow transplantation (BMT) from HLA identical sibling donors (65 patients) or from identical twins (5 patients). All patients were splenectomized before BMT. To prevent graft versus host disease Cyclosporin alone or associated with Methotrexate was given; in addition 13 patients received a T cell depleted marrow. All patients showed engraftment. Of the 5 patients treated by syngenic BMT, 2 patients relapsed but all are alive in remission, 2 of them after a successful second BMT. Of the 36 patients treated by allogeneic BMT in the chronic phase, 20 are alive in unmaintained remission after a median follow-up of 24 months (range 6 to 58). No patients have relapsed. The actuarial survival at 2 years was 60%. Of the 29 patients with more advanced disease, 19 have survived with the actuarial survival at 2 years 50%. We conclude that the probability of cure after BMT is very high, especially if BMT is performed while the patient remains in the chronic phase. Only 3 patients grafted in accelerated or blast phase died with relapse. The main cause of death was interstitial pneumonitis (15 patients) and 10 patients died from other transplant-related complications.
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PMID 
E Gluckman, McMazeron, H Keable, J Meletis, D Bombail, I Jolivet, J J Huart, T Nebout, M Cavazzana, H De Castro (1987)  Prevention and treatment of cytomegalovirus infections after graft of allogenic bone marrow   Nouv Rev Fr Hematol 29: 1. 17-21  
Abstract: Cytomegalovirus (CMV) infection is the most frequent cause of lethal infection after bone marrow transplantation. Viremia occurs in 50% of patients seropositive for CMV before transplantation. Interstitial pneumonitis due to CMV occurs in 10% to 20% of patients with 85% mortality. It is known that CMV infection is due to host reactivation of latent CMV infection or to the transmission of the virus by the marrow donor or by blood transfusions. Treatment of CMV infection has been disappointing in the past. All attempts to treat CMV pneumonia with available agents have failed. Recent studies have indicated the usefulness of prophylactic measures and the early treatment of CMV infections. The use of hyperimmune gammaglobulins has given contradictory results. The selection of seronegative marrow donors or blood donors is useful only if the recipient is seronegative. New antiviral drugs have been used recently in preliminary clinical trials. In preliminary studies a guanosine analogue similar to Acyclovir (DHPG Synthex or BWB 759 U Wellcome) has given reasonable hope of disease cure if it is used early before the occurrence of pneumonia. Phosphonoformate (Foscarnet) has also been shown to be active against CMV infection. Both drugs have good antiviral and clinical action in immunosuppressed patients but the results have been disappointing in cases of pneumonia. Relapse occurs frequently after cessation of the treatment and attempts are being made to use maintenance therapy.
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PMID 
J Meletis, X Yataganas, E Papavasiliou, G Vaiopoulos, P Fessas (1987)  Quantitation of hemoglobin in single erythrocytes with and without fetal hemoglobin.   Eur J Haematol 39: 4. 331-338 Oct  
Abstract: The hemoglobin content was determined by microspectrophotometry in single erythrocytes with and without fetal hemoglobin (Hb F) from 16 normal subjects, 30 patients with anemia of different etiology and severity and 20 individuals with thalassemic disorders. Hb F-containing cells were identified by an indirect immunofluorescent method. The relative single cell value: total extinction (TE) at 415 nm, cell size (A) and the ratio TE/A, were used to indicate single cell values of MCH, MCV and MCHC respectively. The TE (MCH) and/or TE/A (MCHC) did not differ significantly between Hb F-containing (F-cells) and non-F cells in normal subjects and in cases with various forms of acquired anemia. On the contrary, the TE and/or TE/A of F-cells was found significantly higher in F compared to non-F cells in 11 of 20 (55%) of the cases with thalassemia. The results suggest that, in some cases of thalassemia, hemoglobin F is an important substitute for hemoglobin A and may improve the level of hemoglobinization.
Notes:
 
PMID 
E Vilmer, A Rhodes-Feuillette, C Rabian, M Benbunan, J Meletis, A Devergie, J H Bourrhis, J C Gluckman, J C Chermann, E Gluckman (1987)  Clinical and immunological restoration in patients with AIDS after marrow transplantation, using lymphocyte transfusions from the marrow donor.   Transplantation 44: 1. 25-29 Jul  
Abstract: The diagnosis of transfusion-associated acquired immunodeficiency syndrome (AIDS) was made in 2 patients who developed delayed opportunistic infections and severe cytopenias--56 months for the former (patient 1) and 22 months for the latter, (patient 2) following bone marrow transplantation (BMT) for aplastic anemia. In the third case, grafting for acute leukemia (patient 3) (HIV) infection was probably responsible for the failure of hematological and immunological reconstitution 8 months after allogeneic BMT. Each patient received 6 lymphocyte transfusions from the marrow donor for 3 weeks, combined with a 3-month course of low-dose recombinant alpha interferon. This treatment was followed by recombinant gamma interferon for 3 months. We showed that these 3 patients could resume a normal life for 9 months, at least, and that hematological restoration was observed. Our treatment succeeded in correcting the defect of proliferative response to Candida and the impairment of gamma interferon generation for 4 months in one patient and for more than 12 months in the other two recipients. Nevertheless T4 lymphocyte levels increased only slightly and HIV can still be isolated from the patients' blood. At the time of writing, patients 1 and 3 remain in good health with a partial immunological restoration while patient 2 has died of neurological impairment 2 years after the AIDS diagnosis. Although we cannot generalize this successful therapeutic approach to all patients with AIDS, the results may provide an interesting model of the potential effect of lymphocyte transfusions and the role of interferon therapy.
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PMID 
J Meletis, G Arlet, E Dournon, S Pol, A Devergie, C Sportes, M N Peraldi, C Mayaud, Y Perol, E Gluckman (1987)  Legionnaires' disease after bone marrow transplantation.   Bone Marrow Transplant 2: 3. 307-313 Oct  
Abstract: Four patients developed legionnaires' disease after bone marrow transplantation. Two cases occurred early after transplant and were considered as part of a hospital epidemic due to contamination of water supply. The other two cases were considered to be sporadic because they occurred 3-4 weeks after hospital discharge. The outcome was good in two patients. In the third patient, recurrent disease was probably due to acquired resistance to macrolides, and complete cure was achieved after treatment with pefloxacin and rifampicin. The fourth patient died of overwhelming infection despite early treatment with erythromycin and pefloxacin. During the same period we treated 14 patients with pefloxacin for prevention of bacterial infection, of whom none developed Legionella pneumophila infection, while three of the patients reported here were in a group of 11 patients who received only oral non-absorbable antibiotics for gut decontamination. The fourth patient in this report was receiving no antibiotics. Thus pefloxacin seems to be effective as prophylaxis against L. pneumophila infection. When the hospital water supply was heated to 60 degrees C and chlorinated, the nosocomial cases in the hospital completely disappeared.
Notes:
1985
 
PMID 
J Meletis, X Yataganas, G Eliopoulos, J Panourgias, D Loukopoulos, P Fessas (1985)  Hemoglobin content of single erythrocytes from fetuses with parents having heterozygous beta-thalassemia.   Acta Haematol 73: 1. 16-21  
Abstract: The hemoglobin content of single erythrocytes was determined by microspectrophotometry as total extinction (TE) at 415 nm in subjects with a wide spectrum of hemoglobin levels and erythrocyte indices. Precise measurements of the cellular area (A) and the ratio TE/A were also recorded. A significant correlation was found between TE and mean corpuscular hemoglobin (MCH), A and mean corpuscular volume, and TE/A and mean cell hemoglobin concentration (MCHC) for the cases studied. In addition, TE, A and TE/A were determined in fetal erythrocytes obtained by fetoscopy at the 20th week of gestation for prenatal diagnosis of beta-thalassemia. The mean red cell TE and TE/A of the group of fetuses diagnosed to have thalassemia major were significantly lower than those of the group of normal controls and with heterozygous beta-thalassemia. The significant differences of TE, A and TE/A between maternal and fetal blood allowed a safe distinction of the latter. The calculated MCH of the fetuses with thalassemia major was 12% less than that of the normal controls; the respective difference of the mean cell size was 5% and that of MCHC 3% lower than normal.
Notes:
1984
 
PMID 
P Kaklamanis, X Yataganas, J Meletis, K Kyrkoy, P Fessas (1984)  Carcinomatous monoarthritis.   Clin Rheumatol 3: 1. 81-84 Mar  
Abstract: A case of carcinomatous monoarthritis involving the left knee due to carcinoma of the pancreas is described. Lythic lesions of the bones were noted and malignant cells in the synovial fluid have been detected. Needle biopsy of the affected knee did not reveal carcinomatous infiltration of the synovium. The value of the synovial fluid examination for malignant cells in such cases is pointed out.
Notes:
1980
1979
 
PMID 
G Eliopoulos, S Andre, N P Anagnou, J Meletis, B Halpern (1979)  Effect of Corynebacterium parvum on serum lysozyme (muramidase) levels (author's transl)   Experientia 35: 7. 908-909 Jul  
Abstract: An i.v. injection of 548 microgram of killed Corynebacterium parvum into C57B1 mice leads to significant changes in serum lysozyme (muramidase) levels. After an initial fall at 24 h, the activity of the enzyme increased progressively, reached a peak on the 9th day and returned to control range after the 15th day.
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