The evaluation of gene mutation profiles by next-generation sequencing in diffuse large B-cell lymphoma.

OBJECTIVE: Diffuse large B cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma. Although it is a clinically and biologically heterogeneous disease, it is usually treated with R-CHOP chemotherapy. Here, we aimed to investigate gene expression frequency with next-generation sequencing (NGS) and the relation of gene mutations with remission and relapse status in patients with DLBCLs. MATERIALS AND METHODS: We investigated gene mutation profiles by NGS in patients with DLBCL-NOS and analyzed the correlation between gene mutations and response and relapse rates and other clinical indices. RESULTS: Twenty-eight of forty patients were evaluated. The most commonly mutated genes were ANKRD, BRCA1, BRCA2, EZH2, KMTC2, MYC, MYD88, NF1, NOTCH1, PMS2, PTEN, and WRN. The relapse rate was found higher in DLBCL patients with ANKRD26, BRCA2, MYD88, and NOTCH1 mutations. Also, remission duration was found shorter in patients with ANKRD26, BRCA2, and MYD88 mutations. CONCLUSIONS: Our study demonstrates that the presence of some genetic mutations is effective on prognosis in patients with DLBCL. NGS-based evaluation of DLBCL treatment can be used in the future.

The relationship between red cell distribution width and prognostic scores in myelodysplastic syndrome

ABSTRACT Introduction: The myelodysplastic syndrome (MDS) represents a group of hematopoietic neoplasms that is characterized by clonal hematopoiesis, cytopenia and abnormal cellular maturation. Red cell distribution width (RDW) refers to the variation degree of erythrocyte size and it is a reflection of anisocytosis. Higher values have been linked to adverse outcomes, such as increased mortality, vascular events, kidney and liver disease and demonstrated to harbor poor prognosis in solid and hematological malignancies. The RDW value can be used as a contributing parameter for MDS diagnosis, as well as its prognosis. In this study, we essentially aimed to demonstrate the correlation between the RDW and MDS prognostic indexes. Materials and methods: Ninety-four MDS patients at the Aydın Adnan Menderes University Hematology Division were included in the study. The correlations between the RDW and laboratory values (either lactate dehydrogenase, albumin, globulin or ferritin) and the RDW prognostic scoring indexes (IPSS, WPSS, IPSS-R and LR-PSS) were investigated. The PASW for Windows, version 21.0 (SPSS Inc., Chicago, IL, USA), was used for statistical assessment. A p-value below 0.05 was the cut-off for the statistical significance. Results: The mean age of all the patients was 73 ±10 years. Patients were observed for 41.88 ± 25 months. The mean RDW value for all cases was 15.5 ± 2.39. We found a statistically significant difference of survival between RDW values below and above 15.5% (p = 0.016). A significant difference was also observed according to the prognostic scoring indexes (see below). Conclusion: An increase in RDW is probably related to dysplasia in the MDS and this constitutes a possible explanation for the poor outcome. Prognostic indexes might incorporate the RDW as a parameter in the future.

The relationship between red cell distribution width and prognostic scores in myelodysplastic syndrome.

INTRODUCTION: The myelodysplastic syndrome (MDS) represents a group of hematopoietic neoplasms that is characterized by clonal hematopoiesis, cytopenia and abnormal cellular maturation. Red cell distribution width (RDW) refers to the variation degree of erythrocyte size and it is a reflection of anisocytosis. Higher values have been linked to adverse outcomes, such as increased mortality, vascular events, kidney and liver disease and demonstrated to harbor poor prognosis in solid and hematological malignancies. The RDW value can be used as a contributing parameter for MDS diagnosis, as well as its prognosis. In this study, we essentially aimed to demonstrate the correlation between the RDW and MDS prognostic indexes. MATERIALS AND METHODS: Ninety-four MDS patients at the Aydin Adnan Menderes University Hematology Division were included in the study. The correlations between the RDW and laboratory values (either lactate dehydrogenase, albumin, globulin or ferritin) and the RDW prognostic scoring indexes (IPSS, WPSS, IPSS-R and LR-PSS) were investigated. The PASW for Windows, version 21.0 (SPSS Inc., Chicago, IL, USA), was used for statistical assessment. A p-value below 0.05 was the cut-off for the statistical significance. RESULTS: The mean age of all the patients was 73 ±â€¯10 years. Patients were observed for 41.88 ±â€¯25 months. The mean RDW value for all cases was 15.5 ±â€¯2.39. We found a statistically significant difference of survival between RDW values below and above 15.5% (p = 0.016). A significant difference was also observed according to the prognostic scoring indexes (see below). CONCLUSION: An increase in RDW is probably related to dysplasia in the MDS and this constitutes a possible explanation for the poor outcome. Prognostic indexes might incorporate the RDW as a parameter in the future.

COVID-19-associated Evans syndrome: A case report and review of the literature.

Evans syndrome is a rare condition characterized by simultaneous or sequential development of autoimmune hemolytic anemia and immune thrombocytopenia (and/or immune neutropenia). Coronavirus disease 2019 (COVID-19) may cause various hematologic conditions, such as coagulation abnormalities (e.g., bleeding or thrombosis) or cell count alterations (e.g., lymphopenia and neutrophilia). COVID-19 may also induce Evans syndrome via immune mechanisms. Here, we describe the case of a patient developing Evans syndrome shortly after COVID-19 infection. Immune thrombocytopenia and warm-type autoimmune hemolytic anemia developed simultaneously, and intravenous immunoglobulin and methylprednisolone were initially administered. Additionally, we intend to review all COVID-19-induced Evans syndrome cases currently present in the literature and emphasize the differences as well as the similarities regarding patient characteristics, relationship to COVID-19 infection, and treatment approach. Since autoimmune cytopenias are frequent in COVID-19 patients, clinicians should pay particular attention to profound and abrupt-onset cytopenias. In these circumstances, hemolysis markers such as lactate dehydrogenase, haptoglobulin, Coombs tests, etc. should be investigated, and the possibility of Evans syndrome should always be considered to ensure prompt and appropriate treatment. These factors are essential to ensure hematologic recovery and prevent complications such as thrombosis.

Pharmacological dose ascorbic acid administration in relapsed refractory multiple myeloma patients.

OBJECTIVE: High-dose ascorbic acid leads to the formation of highly reactive oxygen species due to the pro-oxidant effect, resulting in cell death; therefore, used as an additive treatment in several malignancies. We present the results obtained by administration of pharmacological dose of ascorbic acid to conventional chemotherapy in relapsed refractory multiple myeloma patients. MATERIALS-METHODS: Intravenous ascorbic acid at a pharmacologic dose of 15 gram/week was added to the chemotherapy regimen of relapsed refractory multiple myeloma patients, who received carfilzomib-lenalidomide-dexamethasone treatment and did not respond after the second cycle. RESULTS: The total of 4 patients who had previously received 6-9 lines of myeloma treatment were included. After 4 cycles of chemotherapy + ascorbic acid combination, 1 patient had a complete response whereas other patients had a very good partial response. CONCLUSION: The addition of pharmacological dose ascorbic acid to conventional chemotherapy can be an effective approach in relapsed refractory patients. Clinical studies with a large number of patients will be useful to evaluate the pharmacological dose of ascorbate in plasma cell disorders.

The association between Hba1c and arterial stiffness among non-diabetic patients with chronic kidney disease.

BACKGROUND: Cardiovascular events are seen more frequently after the age of 60 and they are a significant cause of morbidity and mortality. Arterial stiffness is a property that can be expressed by pulse wave velocity and this value is assumed to be a predictor of cardiovascular events. Patients with chronic kidney disease and dysregulated blood sugar have increased atherosclerosis and arterial stiffness, but the relationship between physiological levels of Hba1c and arterial stiffness is less clear in chronic kidney disease patients without diabetes mellitus. OBJECTIVES: Here, we aimed to investigate the degree of arterial stiffness among non-diabetic, non-dialysis dependent chronic kidney disease patients with physiological HbA1c levels. METHODS: We enrolled 51 patients who were followed up at Ege University Hospital Nephrology Department between February and June 2015. Non-diabetic, non-dialysis dependent chronic kidney disease patients were included in the study. Blood pressure and pulse wave velocity were measured with an applanation tonometry device (Sphygmocor Vx Software Atcor Medical, Australia). Correlations between pulse wave velocity and the aforementioned parameters were investigated (see below). RESULTS: We detected a significant correlation between pulse wave velocity and systolic blood pressure (p=0.0001) and Hba1c (p=0.044) separately. There was an inverse correlation with creatinine clearance (p=0.04). We also detected a significant correlation with serum phosphorus level (p=0.0077) and furosemide use (p=0.014). No correlations were found among the other parameters. CONCLUSIONS: Arterial stiffness is an important predictor of cardiovascular events and measuring it is an inexpensive method for estimating morbidity and mortality. Our study supports the importance of measuring arterial stiffness and of controlling blood glucose levels, even at physiological Hba1c values, especially for chronic kidney disease patients.

CONTEXTO: Os eventos cardiovasculares são mais frequentes em pessoas com mais de 60 anos, e sugere-se que sejam causas significativas de morbidade e mortalidade. A rigidez arterial é expressa pela velocidade da onda de pulso, e presume-se que esse valor seja um preditor de eventos cardiovasculares. Os pacientes com doença renal crônica e desregulação do açúcar no sangue têm aterosclerose e rigidez arterial aumentadas. No entanto, a relação entre os níveis fisiológicos de Hba1c e a rigidez arterial entre pacientes com doença renal crônica sem diabetes melito é menos clara. OBJETIVOS: Buscamos investigar o grau de rigidez entre os pacientes sem diabetes e portadores de doença renal crônica sem dependência de diálise com níveis fisiológicos de HbA1c. MÉTODOS: Incluímos 51 pacientes, sem diabetes e com doença renal crônica sem dependência de diálise, que estavam em acompanhamento no Departamento de Nefrologia do Ege University Hospital entre fevereiro e junho de 2015. A pressão sanguínea e a velocidade da onda do pulso foram medidas com um dispositivo de tonometria de aplanação (Sphygmocor Vx Software Atcor Medical, Austrália). A correlação entre a velocidade da onda de pulso e os parâmetros mencionados anteriormente foi investigada. RESULTADOS: Detectamos correlação significativa entre a velocidade da onda de pulso e a pressão arterial sistólica (p = 0,0001) e Hba1c (p = 0,044) separadamente. Foi constatada correlação inversa com a depuração de creatinina (p = 0,04). Também detectamos correlação significativa com o nível de fósforo sérico (p = 0,0077) e o uso de furosemida (p = 0,014). Não foi encontrada correlação entre outros parâmetros. CONCLUSÕES: A rigidez arterial é um preditor importante de eventos cardiovasculares, e a sua medição é um método de baixo custo para estimar a morbidade e mortalidade. Nosso estudo corrobora a importância da medição da rigidez arterial e do controle dos níveis de glicemia sanguínea mesmo em valores de Hba1c fisiológicos, principalmente para pacientes portadores de doença renal crônica.

Investigation of demographic features, performance, comorbidity status and mortality causes among multiple myeloma patients: real-life data.

BACKGROUND: The demographic characteristics, performance status, frequency of comorbidities and survival rate of patients with multiple myeloma (MM) show variability geographically and different risk scoring systems have been used to assess this population. Here, we present data from a Turkish cohort, focusing on identifying similarities and differences, relative to other reports in the literature. RESEARCH DESIGN AND METHODS: A total of 310 patients diagnosed with MM were enrolled. Their demographic characteristics were investigated retrospectively. For performance assessment; the ECOG-IMWG Myeloma Frailty Score, R-MCI and HCT-SCI scoring indexes were used. PFS and OS periods, as well as the causes of deaths, were determined. RESULTS: The mean age of all study participants was 65 ± 10 years. The mean PFS and OS periods were 24.14± 26.11 and 65.3 ± 4.4 months, respectively. The median R-MCI, CCI and HCT-CI scores were five, four and three points, respectively. Myeloma-related complications were the leading cause of death, with a frequency of 51%. CONCLUSION: Among the scoring systems utilised, R-MCI was more convenient to apply due to its ease of use and practicality. Our study supports the heterogeneous course of myeloma and highlights geographic differences including comorbidities, causes of death and overall survival.

Original Versus Generic Lenalidomide in Patients with Relapsed/Refractory Multiple Myeloma: Comparison of Efficacy and Adverse Events

Objective: Lenalidomide is an effective immunomodulatory derivative drug used in the treatment of multiple myeloma (MM). It is available in original and generic forms in Turkey, but there is no clinical study that has compared the effectiveness and adverse events (AEs) of the generic and original forms of lenalidomide. We compared the effectivity and AEs of generic and original lenalidomide in patients with relapsed/refractory MM (RRMM). Materials and Methods: Patients with RRMM using original or generic lenalidomide were evaluated retrospectively. Overall response (OR), complete response (CR), very good partial response (VGPR), partial response (PR), stable disease, and progressive disease rates and hematologic and nonhematologic AEs were evaluated in these RRMM patients. The results were described as numbers, frequencies, and percentages and were analyzed using PASW 19.0 for Windows with chi-square and Fisher exact tests. Results: The number of patients using original lenalidomide was 55 and the number of patients using generic lenalidomide was 43. The OR rate was 67.2% for patients using original lenalidomide and 60.4% for those on generic lenalidomide. CR and VGPR rates were 14.5% and 45.4% in the original group while the CR and VGPR rates were 20.9% and 18.6%, respectively, in patients using generic lenalidomide. Hematologic AEs were similar in the two groups while some nonhematologic AEs were less common in the original lenalidomide group than the generic group. Only pyrexia as a grade 3-4 AE was more common in the original lenalidomide than the generic lenalidomide group. Conclusion: This study showed that the generic form of lenalidomide has similar efficacy with the original form of lenalidomide in the treatment of RRMM. The AEs of original lenalidomide were generally fewer than those of generic lenalidomide. Further studies involving a larger number of patients with RRMM would be useful for comparing the efficacy and AEs of original and generic lenalidomide.

The association between Hba1c and arterial stiffness among non-diabetic patients with chronic kidney disease / Associação entre Hba1c e rigidez arterial entre pacientes sem diabetes com doença renal crônica

Abstract Background Cardiovascular events are seen more frequently after the age of 60 and they are a significant cause of morbidity and mortality. Arterial stiffness is a property that can be expressed by pulse wave velocity and this value is assumed to be a predictor of cardiovascular events. Patients with chronic kidney disease and dysregulated blood sugar have increased atherosclerosis and arterial stiffness, but the relationship between physiological levels of Hba1c and arterial stiffness is less clear in chronic kidney disease patients without diabetes mellitus. Objectives Here, we aimed to investigate the degree of arterial stiffness among non-diabetic, non-dialysis dependent chronic kidney disease patients with physiological HbA1c levels. Methods We enrolled 51 patients who were followed up at Ege University Hospital Nephrology Department between February and June 2015. Non-diabetic, non-dialysis dependent chronic kidney disease patients were included in the study. Blood pressure and pulse wave velocity were measured with an applanation tonometry device (Sphygmocor Vx Software Atcor Medical, Australia). Correlations between pulse wave velocity and the aforementioned parameters were investigated (see below). Results We detected a significant correlation between pulse wave velocity and systolic blood pressure (p=0.0001) and Hba1c (p=0.044) separately. There was an inverse correlation with creatinine clearance (p=0.04). We also detected a significant correlation with serum phosphorus level (p=0.0077) and furosemide use (p=0.014). No correlations were found among the other parameters. Conclusions Arterial stiffness is an important predictor of cardiovascular events and measuring it is an inexpensive method for estimating morbidity and mortality. Our study supports the importance of measuring arterial stiffness and of controlling blood glucose levels, even at physiological Hba1c values, especially for chronic kidney disease patients.

Resumo Contexto Os eventos cardiovasculares são mais frequentes em pessoas com mais de 60 anos, e sugere-se que sejam causas significativas de morbidade e mortalidade. A rigidez arterial é expressa pela velocidade da onda de pulso, e presume-se que esse valor seja um preditor de eventos cardiovasculares. Os pacientes com doença renal crônica e desregulação do açúcar no sangue têm aterosclerose e rigidez arterial aumentadas. No entanto, a relação entre os níveis fisiológicos de Hba1c e a rigidez arterial entre pacientes com doença renal crônica sem diabetes melito é menos clara. Objetivos Buscamos investigar o grau de rigidez entre os pacientes sem diabetes e portadores de doença renal crônica sem dependência de diálise com níveis fisiológicos de HbA1c. Métodos Incluímos 51 pacientes, sem diabetes e com doença renal crônica sem dependência de diálise, que estavam em acompanhamento no Departamento de Nefrologia do Ege University Hospital entre fevereiro e junho de 2015. A pressão sanguínea e a velocidade da onda do pulso foram medidas com um dispositivo de tonometria de aplanação (Sphygmocor Vx Software Atcor Medical, Austrália). A correlação entre a velocidade da onda de pulso e os parâmetros mencionados anteriormente foi investigada. Resultados Detectamos correlação significativa entre a velocidade da onda de pulso e a pressão arterial sistólica (p = 0,0001) e Hba1c (p = 0,044) separadamente. Foi constatada correlação inversa com a depuração de creatinina (p = 0,04). Também detectamos correlação significativa com o nível de fósforo sérico (p = 0,0077) e o uso de furosemida (p = 0,014). Não foi encontrada correlação entre outros parâmetros. Conclusões A rigidez arterial é um preditor importante de eventos cardiovasculares, e a sua medição é um método de baixo custo para estimar a morbidade e mortalidade. Nosso estudo corrobora a importância da medição da rigidez arterial e do controle dos níveis de glicemia sanguínea mesmo em valores de Hba1c fisiológicos, principalmente para pacientes portadores de doença renal crônica.