Ruxolitinib Reduces Oxidative Stress in Patients With Primary Myelofibrosis: A Multicenter Study.

Introduction Primary myelofibrosis (PM) has a lower overall survival rate than other myeloproliferative neoplasms, and leukemic transformation is the most common cause of death. Increased oxidative stress has an important role in leukemic transformation in these patients. In this study, we aimed to find an answer to the question, "Could Ruxolitinib, which has been widely used in patients with myelofibrosis in recent years, have a role in reducing oxidative stress in these patients?". Methods A total of 106 patients with PM and 111 healthy volunteers were included in this study. We collected the serum samples of healthy volunteers and patients with myelofibrosis at the time of diagnosis and one month after the initiation of Ruxolitinib treatment. Ischemia modified albumin (IMA), native thiol, total thiol, and disulfide levels were studied. The disulfide/native thiol, disulfide/total thiol, and native thiol/total thiol ratios were calculated. Results IMA, native thiol, total thiol, disulfide levels, disulfide/native thiol, and disulfide/total thiol ratios at the time of diagnosis were significantly different in patients with myelofibrosis compared to the control group (p=0.001). Ruxolitinib significantly reduced oxidative stress when the measurements in the first month after Ruxolitinib were compared with those at the time of diagnosis (p=0.001). In patients with ASXL1 mutation, intermediate-2 risk, and high-risk according to the Dipps-plus score, the decrease in oxidative stress in the first month of treatment was more significant than at the time of diagnosis. Conclusion Ruxolitinib may be an effective treatment for reducing oxidative stress in patients with PM. The reduction in oxidative stress parameters with treatment in patients with ASXL1 mutation, intermediate-2, and high-risk patients was observed to be higher.

Thiol/Disulfide Balance in Older Patients with BCR-ABL Negative Myeloproliferative Neoplasms.

BACKGROUND: The trio Essential Thrombocytosis (ET), Polycythemia Vera (PV), and Primary Myelofibrosis (PM) are BCR-ABL negative myeloproliferative neoplasms. All three diseases have the risk of transforming into acute leukemia. Oxidative stress and some genetic mutations increase the risk of leukemic transformation. The median age in patients with ET, PV, and MF is around 64 years, and it is expected to exceed 65 in the coming years. Since oxidative stress increases with age, we aimed to evaluate the oxidative stress parameters in older patients with myeloproliferative neoplasms. METHODS: The study included a total of 160 patients (57 patients with Essential Thrombocytosis, 52 patients with Primary Myelofibrosis, and 51 patients with Polycythemia Vera) and 56 healthy controls, aged 65 and over. Ischemia Modified Albumin (IMA) and thiol parameters (native thiol, total thiol, and disulfide) were studied from serum samples taken at the time of diagnosis. RESULTS: The median age of the patients was 69 (65 - 85) years. Patients had higher levels of IMA and lower levels of thiol compared to the control group (p < 0.001). When evaluated according to disease subgroups, it was observed that the highest IMA levels and the lowest thiol levels were in patients with PM (p < 0.001). Higher IMA levels and lower native thiol levels were found in patients with the ASXL1 mutation (p < 0.001). CONCLUSIONS: Serum IMA and thiol levels are also significantly changed in older patients with BCR-ABL negative myeloproliferative neoplasia. Changes in these markers are independent of age. Disease-associated mutations such as ASXL1 can also affect the serum levels of these markers.

Cardiac Chamber Quantification by Echocardiography in Adults With Sickle Cell Disease: Need Attention to Eccentric Hypertrophy.

Introduction and aim Sickle cell anemia (SCA) is the most common hemoglobinopathy worldwide, and cardiovascular diseases are the most common causes of death. In these patients, cardiac remodeling begins from childhood and leads to sickle cell cardiomyopathy in the following years. Concentric hypertrophy and eccentric hypertrophy are known to predict early cardiac events. This study aims to reveal the relationship between cardiac remodeling types and survival in patients with SCA and investigate the factors that may affect left ventricular mass. Materials and methods A total of 146 patients with SCA were included in the study, and the left ventricular mass index (LVMI) and relative wall thickness (RWT) of the patients were calculated according to echocardiographic measurements, and the patients were categorized into normal, concentric remodeling (CR), concentric hypertrophy (CH), and eccentric hypertrophy (EH) groups. Results The median age of the patients is 32 (18-72). In logistic regression analysis, hemoglobin S (HbS) and ferritin levels were independent predictors for LVMI (p = 0.01 and p < 0.001, respectively). It was observed that 56 (38.4%) of the patients had normal left ventricles, 24 (16.4%) had CR, 21 (14.4%) had CH, and 45 (30.8%) had EH. 31 (21.2%) of the patients died. When we look at the survival curves, there was a statistically significant difference between the four groups (log-rank p < 0.001). It was observed that patients with EH were the group with the lowest probability of survival. Conclusion Cardiac death is one of the most common causes of death in patients with SCA. Early detection of cardiac disorders and starting treatment may be important in reducing mortality in these patients.