Impact of CALR and JAK2V617F Mutations on Clinical Course and Disease Outcomes in Essential Thrombocythemia: A Multicenter Retrospective Study in Turkish Patients.

Objective: In this study, we investigated the effects of calreticulin (CALR) and JAK2V617F mutational status on clinical course and disease outcomes in Turkish patients with essential thrombocythemia (ET). Materials and Methods: Seventeen centers from Türkiye participated in the study and CALR- and JAK2V617F-mutated ET patients were evaluated retrospectively. Results: A total of 302 patients were included, of whom 203 (67.2%) and 99 (32.8%) were JAK2V617F- and CALR-positive, respectively. CALR-mutated patients were significantly younger (51 years vs. 57.5 years, p=0.03), with higher median platelet counts (987x109/L vs. 709x109/L, p<0.001) and lower median hemoglobin levels (13.1 g/dL vs. 14.1 g/dL, p<0.001) compared to JAK2V617F-mutated patients. Thromboembolic events (TEEs) occurred in 54 patients (17.9%), 77.8% of which were arterial. Compared to CALR mutation, JAK2V617F was associated with a higher risk of thrombosis (8.1% vs. 22.7%, p=0.002). Rates of transformation to myelofibrosis (MF) and leukemia were 4% and 0.7%, respectively, and these rates were comparable between JAK2V617F- and CALR-mutated cases. The estimated overall survival (OS) and MF-free survival of the entire cohort were 265.1 months and 235.7 months, respectively. OS and MF-free survival durations were similar between JAK2V617F- and CALR-mutated patients. Thrombosis-free survival (TFS) was superior in CALR-mutated patients compared to JAK2V617F-positive patients (5-year TFS: 90% vs. 71%, respectively; p=0.001). Age at diagnosis was an independent factor affecting the incidence of TEEs. Conclusion: In our ET cohort, CALR mutations resulted in higher platelet counts and lower hemoglobin levels than JAK2V617F and were associated with younger age at diagnosis. JAK2V617F was strongly associated with thrombosis and worse TFS. Hydroxyurea was the most preferred cytoreductive agent for patients with high thrombosis risk.

High-density lipoprotein (HDL) has an impact on myeloma outcome: Lower HDL associates with worse progression-free survival.

BACKGROUND: Multiple myeloma (MM) staging is based on beta­2 MG, albumin, LDH levels, and the presence of chromosomal abnormalities. We aimed to evaluate the impact of high-density lipoprotein (HDL) on myeloma outcomes. MATERIALS AND METHODS: This study included 148 individuals; 68 patients diagnosed with MM and 80 age, sex, comorbidity-matched controls. The relationship between HDL and myeloma stage and the association between HDL and progression-free survival (PFS) were analyzed. RESULTS: Sixty-five percent of patients were male in each group. Mean HDL level was higher in the control group than myeloma group (52.6 ± 15.02 mg/dl versus 33.79 ± 12.71) (p < 0.001). According to ISS, 39 patients (57%) had advanced stage (ISS-III) disease. To assess the optimal cut-point for HDL that makes a difference in PFS, the X­tile software program was used and in line with the created plots, the myeloma cohort was divided into two groups as HDL < 28 and ≥ 28 mg/dl. Twenty-two patients (32.4%) were in HDL < 28 group. According to the ISS, HDL < 28 group had more advanced disease than the HDL ≥ 28 group (p = 0.008). Twenty-nine patients (42.6%) progressed or died during the follow-up and 15 of these were in the HDL < 28 group. Time to progression was shorter in patients who were in the HDL < 28 group (median, 22 versus 40 months, p = 0.03). There was no statistically significant difference between these groups in terms of overall survival (p = 0.708). CONCLUSION: Myeloma patients have lower HDL than controls and HDL < 28 mg/dl associates with advanced-stage disease and shorter PFS. Therefore, HDL can be a surrogate prognostic marker in myeloma.

Treatment options in primary mediastinal B cell lymphoma patients, retrospective multicentric analysis; a Turkish oncology group study.

Introduction and Aim: Primary mediastinal B-cell lymphomas (PMBL) are aggressive B- cell lymphomas. Although the initial treatment models vary in PMBL, appropriate treatment methods are not known. We aim to show real-life data on health outcomes in adult patients with PMBL who received various type of chemoimmunotherapies in Turkey. Method: We analyzed the data of 61 patients who received treatments for PMBL from 2010 to 2020. The overall response rate (ORR), overall survival (OS) and progression-free survival (PFS) of the patients were evaluated. Results: 61 patients were observed in this study. The mean age of the study group was 38.4 ± 13.5 years. From among them, 49.2% of the patients were female (n = 30). For first-line therapy, 33 of them had received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) regimen (54%). Twenty-five patients had received rituximab, etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin (DA-EPOCH-R) regimen. The ORR was 77%. The median OS and PFS were as follows: 25 months (95% CI: 20.4-29.4) and 13 months (95% CI: 8.6-17.3), respectively. The OS and PFS at 12 months were 91.3% and 50%, respectively. The OS and PFS at five years were 64.9% and 36.7%, respectively. Median follow-up time period was 20 months (IQR 8.5-38.5). Conclusion: R-CHOP and DA-EPOCH-R showed good results in PMBL. These remain one of the best determined systemic treatment options for first-line therapy. Also, the treatment was associated with good efficacy and tolerability.

Associations between anemia and insomnia or excessive daytime sleepiness in older adults.

OBJECTIVE: Sleep disorders including excessive daytime sleepiness (EDS), insomnia and anemia are both common. The aim of this study is to investigate associations between anemia and insomnia/EDS in the elderly. METHODS: A total of 744 older outpatients were included in this cross-sectional study. Anemia was defined as a hemoglobin concentration below 12 g/dL in females and <13 g/dl in males. Patients were divided into two groups as anemic and non-anemic. The Epworth Sleepiness Scale score of ≥11 points indicates EDS. Insomnia Severity Index with scores of ≥8 indicates insomnia. RESULTS: The mean age was 79.8±7.7 years. The prevalence of insomnia, EDS and anemia was 62.1%, 23.8%, and 47.2%, respectively. Insomnia (66.3% vs 58.5%) and EDS (29.6% vs 18.6%) were more common in patients with anemia compared to those without anemia (p<0.05). In univariate analysis, there were significant associations between anemia and insomnia [odds ratio (OR):1.4, 95% confidence interval (CI):1.0-1.9], and EDS (OR:1.8,95% CI:1.3-2.6). In multivariate analysis, the relationship between insomnia and nocturia, chronic obstructive pulmonary disease (COPD), and number of drugs used persisted, whereas being male, of an older age, coronary arterial disease, COPD, Parkinson's disease, dementia, and urinary incontinence were associated with EDS (p<0.05), but there was no significant relationships between anemia and insomnia/EDS (p>0.05). CONCLUSION: The present data suggests that an elderly who has anemia is 1.4 times more likely to experience insomnia and 1.8 times more likely to experience EDS than those without anemia.

Prognostic Nutritional Index Predicts Early Mortality in Diffuse Large B-cell Lymphoma.

Objective: The international prognostic index (IPI) and the revised IPI (R-IPI) are used to determine the prognosis in diffuse large B-cell lymphoma (DLBCL). However, these scoring systems are insufficient to identify very high-risk patients. Recently, the prognostic nutritional index (PNI) -calculated with lymphocyte count and albumin- has been used to determine the prognosis in DLBCL. This study aimed to evaluate the effect of PNI score on prognosis and survival in patients with high-risk DLBCL. Methods: Patients diagnosed with DLBCL and treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone were included. Pre-treatment IPI, R-IPI, and PNI scores and progression-free survival (PFS) and overall survival (OS) times were calculated. The cut-off value for PNI according to OS was determined by using the X-Tile program. Results: One hundred and ten patients were included, the median age was 63 years and the median follow-up period was 25 months. According to R-IPI, the median OS could not be reached for the very good risk group, and the median OS values were 83 and 17 months in the good and poor-risk groups, respectively (p=0.001). The cohort was divided into three groups according to the cut-off value for the PNI: patients with PNI <33 were classified as high-risk, 33-42 intermediate-risk, and ≥42 as low-risk. According to PNI, the median durations of PFS and OS were 2 months and 3 months in the high-risk group, 9 months and 19 months in the intermediate-risk group respectively, and in the low-risk group the median duration for PFS and OS could not be reached (p=0.001). Conclusions: The R-IPI is widely used to estimate the prognosis in DLBCL. But in our cohort, in the poor-risk patient group, the OS was 17 months according to R-IPI, while this period was 3 months according to PNI. This finding demonstrated that PNI might predict early mortality in DLBCL.

Are Hematologic Patients Trojan Horse for COVID-19?

Coronavirus disease 2019 (COVID-19) which is caused by severe acute respiratory distress syndrome virus (SARS-CoV-2) continues to affect people all around the world. This study aimed to compare the SARS-CoV-2 viral shedding time between patients diagnosed with hematologic diseases (HD) and a control group. A total of 110 patients were enrolled in this retrospective study; 55 patients with a diagnosis of HD and 55 sex and comorbidity matched controls without a diagnosis of HD, who caught COVID-19 at the same period. Thirty-eight patients were hospitalized in each group. Viral shedding time, COVID-19 severity, need for intensive care unit support, and mortality rates were compared between groups. Median viral shedding time was 24 days in hospitalized HD patients and 12 days in the hospitalized control group (p < 0.01) as 20 days in outpatient HD patients and 10 days in the outpatient control group (p = 0.02). Viral shedding time was longer in severe + critical COVID-19 cases in the whole cohort (median 22 days in severe + critical, and 12 days in mild + moderate) (p < 0.01). Severe + critical COVID-19 was more common in the HD group than the control group (47.2% versus 25.4%, respectively) (p = 0.017). Twenty-five patients were dead in the whole cohort. One patient was in the control group and 24 patients were in the HD group, therefore the mortality rate for the HD group was 43.6%. Because of statistically significant longer viral shedding time, longer-term isolation may be necessary for hematologic patients diagnosed with COVID-19.

Lip necrosis in a patient with paroxysmal nocturnal hemoglobinuria: Can it be triggered by COVID-19?

BACKGROUND: COVID-19 due to SARS-CoV-2 was first described in the city of Wuhan in China and spread around the world turning into a pandemic. COVID-19 can affect different organ systems, including the oral mucosa. AIMS: Although cutaneous involvement has been defined in association with COVID-19, the number of case reports about mucosal involvement by SARS-CoV-2 is limited. Hereby, we report a case of hemorrhagic necrosis on the lip in a patient with paroxysmal nocturnal hemoglobinuria (PNH) and COVID-19 infection and briefly discuss its possible mechanism. PATIENTS: The clinical features and causes of hemorrhagic necrosis on the lip in a woman are presented. RESULTS: In our patient, we think that PNH-associated dermal micro-occlusions caused extensive painful necrosis of the lip. Additionally, COVID-19-induced endothelial damage helped to develop exaggerated hemorrhagic necrosis. CONCLUSION: This current case presentation will contribute to the literature as another case with COVID-19 triggering mucosal involvement.