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1.
Front Oncol ; 13: 1128994, 2023.
Article in English | MEDLINE | ID: mdl-36959785

ABSTRACT

Thrombosis is the most common and a life-threatening complication in patients with Paroxysmal Nocturnal Hemoglobinuria. One-third of patients with PNH experience at least one thromboembolic event during the course of the disease, with thrombosis being the most common cause of death in these patients. The mechanism of thrombosis in PNH is complex and continues to be of great research interest. Since the introduction of C5 complement inhibitors in the treatment of PNH, the incidence of thromboembolic events has decreased substantially. We retrospectively analyzed data concerning the thrombotic episodes of 41 patients with PNH from 14 different national hematology centers in Greece. Sixteen patients (39%) experienced at least one episode of thrombosis, including, seven (43.8%) at diagnosis, seven (43.8%) during the course of the disease and two (12.5%) patients prior to PNH diagnosis. Nearly half of these individuals (n=7, 43.8%) had multiple episodes of thrombosis during the course of their disease. The most common sites of thrombosis were intra-abdominal veins. Three out of 26 patients developed thrombosis while on eculizumab. In none of the 16 patients, the thrombotic event was fatal. Our findings, despite the small number of patients, confirmed that thrombosis continues to be a significant complication of PNH affecting more than one third of the patients.

2.
J Laryngol Otol ; 137(2): 222-224, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36380501

ABSTRACT

OBJECTIVE: This article presents the case of an adolescent with asymptomatic coronavirus disease 2019 infection who had vestibular neuronitis symptoms. METHOD AND RESULTS: The new coronavirus disease 2019 demonstrates neurotropic properties, apart from airway symptoms. Early in the pandemic, coronavirus disease 2019 infection had been associated with olfactory disturbances. Accumulative evidence supports that both the infection with coronavirus disease 2019 and the vaccination against the virus may induce a condition of vestibular hypofunction, known as vestibular neuronitis. Coronavirus disease 2019 may directly affect the vestibular organs and ganglia, or indirectly damage them via immune-mediated mechanisms. In most cases, complete recovery is achieved with the typical therapeutic approaches for vestibular neuronitis, consisting of supportive measures and corticosteroids. CONCLUSION: Physicians may expect an increased incidence of vestibular neuronitis during the coronavirus disease 2019 pandemic. Conversely, coronavirus disease 2019 infection should be considered in patients with sudden vestibular symptoms.


Subject(s)
COVID-19 , Vestibular Neuronitis , Vestibule, Labyrinth , Adolescent , Humans , Child , Vestibular Nerve , COVID-19/complications
3.
Curr Res Transl Med ; 70(2): 103330, 2022 05.
Article in English | MEDLINE | ID: mdl-34979486

ABSTRACT

PURPOSE: MALT lymphoma is thought to have a genetic component. Genetic studies in the greek population are rare and genetic determinants remain to be established. The current study aimed to seek correlations between genetic polymorphisms and risk of MALT lymphoma in the Greek population. PATIENTS AND METHODS: 83 MALT lymphoma patients and 60 age-matched healthy outpatients were recruited. SNPs in TNFa, LTA and CTLA-4 genes and IL1RN-VNTR and GSTT1 and GSTTM1 null polymorphisms were genotyped using published PCR/PCR-RFLP methods, while two novel PCR-RFLP methods were developed for IL-22 rs7314777 and TCF19 rs7750641 SNPs. Part of the results was validated by DNA-sequencing. Statistical analysis was performed using SPSS and the SNPstats bioinformatic tool. RESULTS: The mean age of the patients and controls were 55.9 and 56.2 years respectively. The majority of patients (63) suffered gastric marzinal zone lymphoma (GMZL) and 71.1% were stage I at diagnosis. A statistically significant association was noted for the CTLA-4 49A/ G G variant (OR:2.56,p: 0.006) and the TCF19 rs7750641 SNP T variant (OR: 3.86, p:0.023). CONCLUSIONS: Our study confirmed a role for CTLA-4 49A/G and TCF19 rs7750641 SNPs in the Greek population. Additional studies could help confirm these associations and possibly link them to prognosis or response to treatment parameters.


Subject(s)
Lymphoma, B-Cell, Marginal Zone , CTLA-4 Antigen/genetics , Genetic Predisposition to Disease , Greece/epidemiology , Humans , Lymphoma, B-Cell, Marginal Zone/epidemiology , Lymphoma, B-Cell, Marginal Zone/genetics , Lymphoma, B-Cell, Marginal Zone/pathology , Lymphoma, Non-Hodgkin , Middle Aged , Polymorphism, Single Nucleotide , Stomach Neoplasms , Transcription Factors
4.
Clin Transl Oncol ; 22(7): 1059-1066, 2020 Jul.
Article in English | MEDLINE | ID: mdl-31696413

ABSTRACT

PURPOSE: Cutaneous T cell lymphomas (CTCL) are rare and histologically diverse lymphoproliferative neoplasms, with mycosis fungoides (MF) representing the most common disease subset. Given the emerging role of myeloid-derived suppressor cells (MDSC) as a clinically applicable biomarker in solid tumors, we sought to investigate the presence of tumor-infiltrating and circulating MDSC in early- and advanced-stage MF patients and evaluate their prognostic significance in patient overall survival. METHODS: Tumor-infiltrating MDSC were assessed immunohistochemically with Arginase-1 in 31 MF and 14 non-MF skin punch biopsies. Circulating MDSC were assessed with flow cytometry in freshly isolated PBMC from 29 MF patients. Granulocytic MDSC (G-MDSC) were defined as CD11b+CD14-CD15+ and monocytic MDSC (M-MDSC) were defined as CD11b+CD14+HLA-DRlow/-. RESULTS: MDSC infiltration occurred in approximately one-third (35.5%) of CTCL lesions, with a predilection for non-MF lesions (p < 0.05). The predominant morphology of MDSC was granulocytic. Although in MF lesions the presence of MDSC infiltrates did not correlate with clinical stage, it conferred significantly worse overall survival outcomes (p < 0.05). Circulating G-MDSC were significantly higher in MF patients compared to healthy donor controls (p < 0.0001), while M-MDSC did not show any statistically significant difference. G-MDSC were significantly higher in patients with active disease compared to patients who were in partial remission (p < 0.01). As with tumor-infiltrating MDSC, clinical stage did not correlate with circulating G-MDSC levels, while prospective overall survival analysis showed that patients with high levels of circulating G-MDSC have significantly inferior outcomes (p < 0.01). CONCLUSIONS: This study shows that G-MDSC could represent a novel and easily assessable biomarker in MF, which mirrors disease activity and can predict patient subgroups with aggressive clinical features.


Subject(s)
Mycosis Fungoides/pathology , Myeloid-Derived Suppressor Cells/pathology , Skin Neoplasms/pathology , CD11b Antigen , Cell Count , Female , Flow Cytometry , Granulocytes/metabolism , Granulocytes/pathology , HLA-DR Antigens , Humans , Immunohistochemistry , Lewis X Antigen , Lipopolysaccharide Receptors , Male , Monocytes/metabolism , Monocytes/pathology , Myeloid-Derived Suppressor Cells/metabolism , Neoplasm Staging , Prognosis , Survival Rate
5.
Med Oral Patol Oral Cir Bucal ; 24(3): e379-e384, 2019 May 01.
Article in English | MEDLINE | ID: mdl-31011138

ABSTRACT

BACKGROUND: The objective of this study was to describe the oral health status of Cystic Fibrosis (CF) children in a US facility. MATERIAL AND METHODS: Twenty CF children ages 6-18 were recruited from Children's Hospital of Wisconsin Pulmonary Clinic. Parents completed a health questionnaire. Clinical examinations checked dental caries using the dmft/DMFT index, dental hygiene using the Simplified Greene-Vermillion Index (DI-S), gingival inflammation using the Community Periodontal Index of Treatment Needs, and enamel defects using the modified Developmental Defects of Enamel Index. RESULTS: The majority (90%) brush twice a day, 65% consume sugary snacks, and 70% visit the dentist every 6 months. Clinically, they presented DMFT 0.25 and dmft 0.90, fair oral hygiene with DI-S 1.02, 75% had mild gingivitis and 50% had enamel defects. The more antibiotics they took, significantly more frequent (p=0.007) and more severe (p=0.017) enamel defects were noted. Similar trend was found between the number of surgeries and the presence of enamel defects (p=0.076) and dental caries (p=0.028). CONCLUSIONS: Within the limitations of this study, CF patients were found to be at oral health risk due to the high prevalence of dental enamel defects. Oral health for CF children should be part of the multidisciplinary care.


Subject(s)
Cystic Fibrosis , Dental Caries , Adolescent , Child , DMF Index , Humans , Oral Health , Oral Hygiene , Pilot Projects , Prevalence , United States
8.
Eur Arch Paediatr Dent ; 17(3): 205-10, 2016 Jun.
Article in English | MEDLINE | ID: mdl-26645986

ABSTRACT

BACKGROUND: Ectodermal dysplasia (ED) represents a disorder group characterised by abnormal development of the ectodermal derivatives. Removable partial dentures (RPD), complete dentures (CD) or overdentures (OD) are most often the treatment of choice for young affected patients. Prosthetic intervention is of utmost importance in the management of ED patients, as it resolves problems associated with functional, aesthetic, and psychological issues, and improves a patient's quality of life. However, few studies present the principles and guidelines that can assist in the decision-making process of the most appropriate removable prosthesis. The purpose of this study was to suggest a simple treatment decision-making algorithm for selecting an effective and individualised rehabilitative treatment plan, considering different parameters. CASE REPORTS: The cases and treatment of two young ED patients are described and each one was treated with either RPDs or ODs. FOLLOW-UP: Periodic recalls were employed to manage problems, and monitor the changes associated with occlusion and fit of the prostheses in relation to each patient's growth. Both patients were followed up for more than 2 years and reported significant improvement in their appearance, masticatory function, and social behaviour as a result of the prosthetic rehabilitation. CONCLUSION: The main factors guiding the decision process towards the choice of an RPD or an OD are the presence of posterior natural teeth, facial aesthetics, lip support, number and size of existing natural teeth, and the occlusal vertical dimension.


Subject(s)
Anodontia/rehabilitation , Denture, Overlay , Denture, Partial, Removable , Ectodermal Dysplasia , Algorithms , Anodontia/diagnostic imaging , Child, Preschool , Humans , Male
9.
Leukemia ; 30(1): 238-42, 2016 Jan.
Article in English | MEDLINE | ID: mdl-25971363
11.
Clin Microbiol Infect ; 20(1): O50-7, 2014 Jan.
Article in English | MEDLINE | ID: mdl-23889746

ABSTRACT

Invasive candidiasis is a life-threatening infection in patients with haematological malignancies. The objective of our study was to determine the incidence, microbiological characteristics and clinical outcome of candidaemia among hospitalized adult patients with haematological malignancies. This is a population-based, prospective, multicentre study of patients ≥ 18 years admitted to haematology and/or haematopoietic stem cell transplantation units of nine tertiary care Greek hospitals from January 2009 through to February 2012. Within this cohort, we conducted a nested case-control study to determine the risk factors for candidaemia. Stepwise logistic regression was used to identify independent predictors of 28-day mortality. Candidaemia was detected in 40 of 27,864 patients with haematological malignancies vs. 967 of 1,158,018 non-haematology patients for an incidence of 1.4 cases/1000 admissions vs. 0.83/1000 respectively (p <0.001). Candidaemia was caused predominantly (35/40, 87.5%) by non-Candida albicans species, particularly Candida parapsilosis (20/40, 50%). In vitro resistance to at least one antifungal agent was observed in 27% of Candida isolates. Twenty-one patients (53%) developed breakthrough candidaemia while receiving antifungal agents. Central venous catheters, hypogammaglobulinaemia and a high APACHE II score were independent risk factors for the development of candidaemia. Crude mortality at day 28 was greater in those with candidaemia than in control cases (18/40 (45%) vs. 9/80 (11%); p <0.0001). In conclusion, despite antifungal prophylaxis, candidaemia is a relatively frequent infection associated with high mortality caused by non-C. albicans spp., especially C. parapsilosis. Central venous catheters and hypogammaglobulinaemia are independent risk factors for candidaemia that provide potential targets for improving the outcome.


Subject(s)
Candida/classification , Candidemia/epidemiology , Candidemia/etiology , Hematologic Neoplasms/complications , Adolescent , Adult , Agammaglobulinemia/drug therapy , Aged , Aged, 80 and over , Antifungal Agents/therapeutic use , Candidemia/microbiology , Candidemia/mortality , Case-Control Studies , Central Venous Catheters/adverse effects , Female , Greece/epidemiology , Hospitalization , Humans , Logistic Models , Male , Middle Aged , Prospective Studies , Risk Factors , Young Adult
12.
Orthod Craniofac Res ; 15(2): 71-83, 2012 May.
Article in English | MEDLINE | ID: mdl-22515183

ABSTRACT

OBJECTIVES: To evaluate the effectiveness of non-steroidal anti-inflammatory drugs (NSAIDs) in managing pain arising from orthodontic interventions, such as archwire or separators placement. DATA SOURCES: Medline and Cochrane databases searched in February 2010 and updated in July 2010 using orthodontics and pain as the search terms. Additional studies located from Google Scholar, Clinical Trials and the reference lists of retrieved articles. STUDY SELECTION: Randomized controlled trials comparing NSAID to placebo using visual analogue scale (VAS) scores. DATA SYNTHESIS: Of the 1127 studies identified through database searches, seven were included for meta-analysis. Treatment effects (Hedges' g using random effects model) and 95% confidence intervals (CI) of the pain VAS scores were evaluated at 2, 6 and 24 h after intervention, during chewing and biting activities. Pain level at 2 h differed between the ibuprofen and placebo groups during biting (95% CI: -0.178 to -0.046), but not during chewing (95% CI: -0.551 to 0.148). At 6 h, the ibuprofen group exhibited lower pain levels during both activities (chewing 95% CI: -0.640 to -0.123, biting 95% CI: -0.857 to -0.172). At 24 h, no statistically significant difference could be detected between ibuprofen and placebo (chewing 95% CI: -0.642 to 0.112, biting 95% CI: -0.836 to 0.048). No statistically significant difference was found between ibuprofen and acetaminophen at any time point. CONCLUSION: Ibuprofen appears to lower orthodontic pain compared to placebo at 2 and 6 h after separators or archwire placement, but not at 24 h, when pain peaks.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Facial Pain/drug therapy , Ibuprofen/therapeutic use , Orthodontic Appliances/adverse effects , Orthodontics, Corrective/adverse effects , Acetaminophen/therapeutic use , Bite Force , Facial Pain/etiology , Humans , Mastication , Pain Measurement , Randomized Controlled Trials as Topic
14.
West Indian Med J ; 58(1): 61-4, 2009 Jan.
Article in English | MEDLINE | ID: mdl-19566000

ABSTRACT

A 51-year old male patient with a three-month history of constant and dull left flank pain was investigated by ultrasonography, computed tomography (CT) scan and magnetic resonance imaging (MRI) of the abdomen, which disclosed a 8 x 7 x 6 cm retroperitoneal pararenal mass with heterogeneous imaging characteristics and bright enhancement following intravenous contrast injection. Based on the hypervascularity of the mass and the lack of specific signs in the imaging investigation, lymphoma, sarcoma or vascular tumour were considered as probable, diagnoses and the patient underwent an exploratory laparotomy. The histologic examination of the surgically resected specimen disclosed "a hyaline type of Castleman's disease". Further evaluation of the patient with antibody testing for HIV 1 and 2, as well as viral load by PCR for Herpes Virus-8 (HHV-8) were negative. Bone marrow aspiration, biopsy and immunophenotypic study did not disclose any evidence of lymphoma. Molecular study of the bone marrow for immunoglobulin heavy chain rearrangement showed a polyclonal pattern; serum protein electrophoresis did not show any evidence of hypergammaglobulinaemia and serum immunofixation electrophoresis did not show any monoclonal protein. A diagnosis of localized-unicentric type of Castleman's disease was made. Castleman's Disease should be included in the differential diagnosis of any solitary, heterogeneous and hypervascular retroperitoneal mass. Discovery of Castleman's disease at any area of the body should be followed by a thorough imaging and laboratory work-up in order to exclude the multicentric type of the disease and the co-existence of lymphoma.


Subject(s)
Castleman Disease/diagnosis , Retroperitoneal Neoplasms/diagnosis , Castleman Disease/pathology , Castleman Disease/surgery , Contrast Media , Diagnosis, Differential , Diagnostic Imaging , Humans , Male , Middle Aged , Retroperitoneal Neoplasms/pathology , Retroperitoneal Neoplasms/surgery
15.
Arch Oral Biol ; 54(7): 666-70, 2009 Jul.
Article in English | MEDLINE | ID: mdl-19463988

ABSTRACT

OBJECTIVE: Fluctuating dental asymmetry is considered a sensitive indicator of environmental stress. We used fluctuating asymmetry of teeth in Greek children to assess the effect of the Chernobyl accident to the Greek population, which received relatively large radiation exposure compared to other European countries. DESIGN: Sixty dental casts were divided into two groups according to date of birth prior to or after the Chernobyl accident. The intercuspal distances of the mandibular first permanent molars were measured with digital calipers. We followed the data analysis procedure proposed by Palmer and Strobeck (2003). RESULTS: Fluctuating asymmetry was found at levels above measurement error in all traits except for the buccal measurement. Overall, there were no significant differences in the fluctuating asymmetry between the two groups, after removal of outliers. CONCLUSIONS: These results suggest that environmental radioactivity from the Chernobyl incident did not significantly affect the symmetry of lower permanent molar intercuspal distances in the specific population, even though increased levels of radionuclides have been reported in teeth and other tissues.


Subject(s)
Chernobyl Nuclear Accident , Molar/abnormalities , Radioactive Pollutants/adverse effects , Greece , Humans , Mandible , Models, Dental , Molar/radiation effects , Odontometry , Radiation Dosage , Tooth Crown/abnormalities , Tooth Crown/radiation effects
16.
West Indian med. j ; 58(1): 61-64, Jan. 2009. ilus
Article in English | LILACS | ID: lil-672437

ABSTRACT

A 51-year old male patient with a three-month history of constant and dull left flank pain was investigated by ultrasonography, computed tomography (CT) scan and magnetic resonance imaging (MRI) of the abdomen, which disclosed a 8 x 7 x 6 cm retroperitoneal pararenal mass with heterogeneous imaging characteristics and bright enhancement following intravenous contrast injection. Based on the hypervascularity of the mass and the lack of specific signs in the imaging investigation, lymphoma, sarcoma or vascular tumour were considered as probable diagnoses and the patient underwent an exploratory laparotomy. The histologic examination of the surgically resected specimen disclosed "a hyaline type of Castleman's disease". Further evaluation of the patient with antibody testing for HIV 1 and 2, as well as viral load by PCR for Herpes Virus-8 (HHV-8) were negative. Bone marrow aspiration, biopsy and immunophenotypic study did not disclose any evidence of lymphoma. Molecular study of the bone marrow for immunoglobulin heavy chain rearrangement showed a polyclonal pattern; serum protein electrophoresis did not show any evidence of hypergamma-globulinaemia and serum immunofixation electrophoresis did not show any monoclonal protein. A diagnosis of localized - unicentric type of Castleman's disease was made. Castleman's Disease should be included in the differential diagnosis of any solitary, heterogeneous and hypervascular retroperitoneal mass. Discovery of Castleman's disease at any area of the body should be followed by a thorough imaging and laboratory work-up in order to exclude the multicentric type of the disease and the co-existence of lymphoma.


Un paciente varón de 51 años con una historia de tres meses de dolor constante y sordo en el costado izquierdo, fue sometido a investigación mediante ultrasonografía, tomografía axial computarizada (IAC) e imagen por resonancia magnética (IRM) del abdomen. La investigación reveló una masa retro-peritoneal pararenal de 8 x 7 x 6 cm, con imagen de características heterogéneas y aumento de la luminosidad tras la inyección intravenosa de contraste. Sobre la base de hipervascularidad de la masa y la falta de signos específicos en la investigación por imágenes, el linfoma, el sarcoma o el tumor vascular fueron considerados como diagnósticos probables y el paciente fue sometido a una laparotomía exploratoria. El examen histológico del espécimen resecado quirúrgicamente reveló "un tipo hialino de la enfermedad de Castleman." La evaluación ulterior del paciente con prueba de anticuerpos de VIH 1 y 2, así como la carga viral por PCR para la detección del virus herpes humano tipo 8, dio resultados negativos. La aspiración de médula ósea, la biopsia y el estudio inmunofenotípico no mostraron ninguna evidencia de linfoma. El estudio molecular de la médula ósea para el reordenamiento de la cadena pesada de inmunoglobulina mostró un patrón policlonal. La electro-foresis de la proteína en suero no mostró evidencia alguna de hipergammaglobulinemia y la electroforesis de inmunofijación sérica no mostró proteína monoclonal alguna. Se hizo un diagnóstico de tipo unicéntrico y localizado de la enfermedad de Castleman. La Enfermedad de Castleman debe incluirse en el diagnóstico diferencial de cualquier masa retroperitoneal solitaria, heterogénea e hipervascular. El descubrimiento de la enfermedad de Castleman en cualquier área del cuerpo debe ser seguido de un examen por imágenes completo y pruebas exhaustivas de laboratorio, a fin de eliminar la posibilidad de un tipo multicéntrico de la enfermedad y la co-existencia de un linfoma.


Subject(s)
Humans , Male , Middle Aged , Castleman Disease/diagnosis , Retroperitoneal Neoplasms/diagnosis , Contrast Media , Diagnosis, Differential , Diagnostic Imaging , Castleman Disease/pathology , Castleman Disease/surgery , Retroperitoneal Neoplasms/pathology , Retroperitoneal Neoplasms/surgery
17.
Hematol Oncol ; 25(3): 127-31, 2007 Sep.
Article in English | MEDLINE | ID: mdl-17514771

ABSTRACT

Splenectomy has traditionally been considered as a standard first line treatment for splenic marginal zone lymphoma (SMZL) conferring a survival advantage over chemotherapy. However it carries significant complications, especially in elderly patients. The purpose of this retrospective study was to report our experience on the efficacy of Rituximab as first line treatment in 16 consecutive SMZL patients, diagnosed in our department. The diagnosis was established using standard criteria. Patients' median age was 57 years (range, 48-78). Prior to treatment initiation all patients had splenomegaly, nine had anemia, five lymphocytosis, five neutropenia and six thrombocytopenia. Rituximab was administered at a dose of 375 mg/m2/week for 6 consecutive weeks. The overall response rate was 100%. After treatment, all patients had a complete resolution of splenomegaly along with restoration of their blood counts. Eleven patients (69%) achieved a CR, three (19%) unconfirmed CR and two (12%) a PR. Among the complete responders seven patients had also a molecular remission. The median time to clinical response was 3 weeks (range, 2-6). Rituximab maintenance was given to 12 patients. Eleven of them had no evidence of disease progression after a median follow-up time of 28.5 months (range, 14-36), while two out of four patients who did not receive maintenance, relapsed 7 and 24 months after the completion of induction treatment. Median follow-up time for the entire series was 29.5 months (range, 15-81). No deaths were recorded during the follow-up period. Therapy was well tolerated. The present study demonstrates that rituximab is an effective treatment for SMZL and could be considered as a substitute or alternative to splenectomy.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Antineoplastic Agents/therapeutic use , Lymphoma, B-Cell/drug therapy , Lymphoma, Non-Hodgkin/drug therapy , Splenic Neoplasms/drug therapy , Aged , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal, Murine-Derived , Drug Administration Schedule , Drug Evaluation , Female , Humans , Male , Middle Aged , Remission Induction , Retrospective Studies , Rituximab , Treatment Outcome
18.
Anticancer Res ; 26(2A): 1201-7, 2006.
Article in English | MEDLINE | ID: mdl-16619525

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.


Subject(s)
Leukemia, Promyelocytic, Acute/genetics , Point Mutation , fms-Like Tyrosine Kinase 3/genetics , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bone Marrow/metabolism , Codon , Humans , Leukemia, Promyelocytic, Acute/drug therapy , Leukemia, Promyelocytic, Acute/metabolism , Neoplasm Proteins/biosynthesis , Neoplasm Proteins/genetics , Oncogene Proteins, Fusion/biosynthesis , Oncogene Proteins, Fusion/genetics , Pilot Projects , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , Tandem Repeat Sequences , fms-Like Tyrosine Kinase 3/biosynthesis
19.
Leukemia ; 19(6): 894-900, 2005 Jun.
Article in English | MEDLINE | ID: mdl-15800675

ABSTRACT

The significance of angiogenesis in Hodgkin's lymphoma (HL) is not well defined. The aim of this study was to evaluate various morphometric characteristics of microvessels in lymph node sections of 286 patients with HL at diagnosis and investigate their relationship with clinicopathologic parameters and prognosis. Microvessel density (MVD), total vascular area (TVA) and several size- and shape-related microvascular parameters were quantitated--after anti-CD34 immunohistochemical staining--in the region of most intense vascularization, using image analysis. An increase in microvessel caliber parameters (area, perimeter, major and minor axis length) and a decrease in MVD were noted with increasing stage. An inverse relationship was recorded between MVD and the number of involved sites (NIS) and LDH. In univariate analysis, overall disease-specific survival was adversely affected by MVD and TVA, whereas inferior failure-free survival (FFS) was associated with the presence of more flattened vessel sections. Multivariate analysis disclosed that the extent of angiogenesis (MVD/TVA), age and the NIS independently affected overall survival. Accordingly, FFS was independently linked to the shape of microvessels and albumin levels or the NIS. In conclusion, our data support the view that angiogenesis in HL provides independent prognostic information, requiring the concomitant evaluation of quantitative and qualitative aspects of microvascular network.


Subject(s)
Hodgkin Disease/mortality , Hodgkin Disease/pathology , Neovascularization, Pathologic/mortality , Neovascularization, Pathologic/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Antigens, CD34/metabolism , Female , Humans , Immunohistochemistry , Male , Microcirculation , Middle Aged , Neovascularization, Pathologic/metabolism , Prognosis , Retrospective Studies , Survival Analysis
20.
J BUON ; 10(1): 59-69, 2005.
Article in English | MEDLINE | ID: mdl-17335133

ABSTRACT

PURPOSE: Serum beta-2 microglobulin (sbeta(2)m) is an established prognostic factor for several lymphoproliferative disorders. Because its significance in Hodgkin's lymphoma (HL) is controversial, we determined sbeta(2)m levels in pretreatment serum samples of patients with HL in order to elucidate its prognostic value in this condition. PATIENTS AND METHODS: Pretreatment sbeta(2)m levels were determined in 379 HL patients who were treated with ABVD or equivalent regimens with or without radiotherapy (RT), using a radioimmunoassay (upper normal limit 2.4 mg/l). Sbeta(2)m levels were correlated with several clinical and laboratory parameters. RESULTS: Elevated sbeta(2)m levels were detected in 138/379 (36%) patients and correlated with all clinical and laboratory baseline features except gender, lung involvement and mediastinal bulk. They also correlated with serum soluble CD30 and interleukin-10 levels. The 8-year failure-free survival (FFS) was 78 -/+ 4% for patients with normal versus 65 -/+ 7% for patients with elevated sbeta(2)m levels (p=0.003). The corresponding rates among early-stage patients were 83 -/+ 53% versus 71 -/+ 9% (p=0.003), while for advanced stages they were 70 -/+ 6% versus 64 -/+ 8% (p=0.54). In multivariate analysis of the whole patient population elevation of sbeta(2)m levels was not predictive of FFS, but it was strongly predictive among early-stage patients. The 8-year overall survival (OS) rates were 91 -/+ 3% for patients with normal versus 59 -/+ 11% (p <0,0001) for patients with elevated sbeta(2)m levels, while unrelated mortality at 8 years was 1 -/+ 1% versus 27 -/+ 12% (p<0.0001). CONCLUSION: Our data suggest that sbeta(2)m levels may be a potent prognostic factor for FFS in patients with early stage HL treated with ABVD and equivalent regimens. Their effect on OS is confounded by the higher unrelated mortality in patients with elevated baseline sbeta(2)m levels, probably due to the strong association between sbeta(2)m and older age.

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