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.

Current and emerging tyrosine kinase inhibitors for the treatment of chronic myeloid leukemia in young adults.

INTRODUCTION: Chronic myeloid leukemia (CML) is more common in older adults, but nearly 15-20% of the patients is between 15 and 39 years of age. In this age group, patients may seek clinical care a much later period of the disease and they may have a heavier burden of disease. In addition, young patients with CML may face unique challenges related to their age, such as concerns about health care, fertility, or careers. The current standard of care for CML is the use of tyrosine kinase inhibitors (TKIs), which induce remission in most young patients and can achieve long-term disease control. AREAS COVERED: This review summarizes age-specific treatment-related conditions, as well as the effectiveness of TKI therapy in this age group. PubMed, Google Scholar, clinicaltrials.gov and other abstract databases were used while preparing this review. The period of 2001-2023 was chosen as the search window. EXPERT OPINION: Although we do not have sufficient data, young adult population has a special importance for TKI treatment. Clinical features, efficacy of treatments, and specific conditions in this age group should attract more attention of clinicians and more intensive studies should be conducted in the future.

Correction to: Efects of AGEs, sRAGE and HMGB1 on Clinical Outcomes in Multiple Myeloma.

[This corrects the article DOI: 10.1007/s12288-022-01574-6.].

Effects of AGEs, sRAGE and HMGB1 on Clinical Outcomes in Multiple Myeloma.

Purpose: The receptor for advanced glycation end products (RAGE) upregulated during the onset and progression of cancer and bone-related pathologies. In this study, we aimed to investigate the role of serum advanced glycation end products (AGEs), soluble RAGE (sRAGE) and high mobility group box 1 (HMGB1), in multiple myeloma (MM). Methods: AGEs, sRAGE and HMGB1 concentrations of 54 newly diagnosed MM patients and 30 healthy volunteers were measured by ELISA. The estimations were done only once at diagnosis. The medical records of the patients were evaluated. Results: There was no significant difference between the AGEs and sRAGE levels between the patient and control groups (p = 0.273, p = 0.313). In ROC analysis, a HMGB1 cutoff value of > 9170 pg/ml accurately discriminated MM patients (AUC = 0.672, 95% CI 0.561-0.77, p = 0.0034). AGEs level was found to be significantly higher in early-stage disease and HMGB1 in advanced disease (p = 0.022, p = 0.026). High HMGB1 levels were detected in patients whose with better first-line treatment response (p = 0.019). At 36 months, 54% of patients with low AGE were alive, compared to 79% of patients with high AGE (p = 0.055). Patients with high HMGB1 levels tended to have a longer PFS (median 43 mo [95% CI; 20.68-65.31] ) compared to patients with low HMGB1 levels (median 25 mo [95% CI; 12.39-37.6], p = 0.054). Conclusion: In this study, a significant elevation of serum HMGB1 level was found in MM patients. In addition, the positive effects of RAGE ligands on treatment response and prognosis were determined.

Evaluation of a Generic Bortezomib Molecule in Newly Diagnosed Multiple Myeloma Patients

Objective: Constantly increasing health expenditures lead to the use of generic molecules and generic versions of bortezomib have been used for a long time. The aim of this study is to retrospectively examine the effectiveness, side effects, and reliability of generic bortezomib in newly diagnosed multiple myeloma (MM) patients. Materials and Methods: The data of 95 patients who received four cycles of bortezomib as first- or second-line therapy in a single center were retrospectively recorded. Treatment responses, side effects, and progression-free survival (PFS) rates were calculated and compared. Results: Of the 95 patients, 42 used the original and 53 used the generic molecule. Epidemiological data, MM types, genetic risk groups, laboratory values at diagnosis, and bortezomib treatment lines (as a first line or second) were evaluated and there was no statistical difference between the two groups. When the response rates were evaluated according to International Myeloma Working Group criteria, there was no significant difference (p=0.42). Rates of partial response and higher responses were similar (81% vs. 79.2%, p=0.84). PFS rates were 42.8 months with the original and 37.8 months with the generic molecule (p=0.68). Side effects were seen in 44.2% of all patients, and the most common side effects were neuropathy, cytopenia, and infection. These rates were similar in the two groups (p=0.55). Conclusion: Although this retrospective study is limited in scope, it is the first study comparing the original molecule of bortezomib with a generic version. There were no statistical differences between the two groups in terms of treatment responses, PFS, or side effects. However, large-scale evaluations will help obtain more data on this subject.

Serum calprotectin (S100A8/A9) levels as a new potential biomarker of treatment response in Hodgkin lymphoma.

INTRODUCTION: Hodgkin lymphoma (HL) is unusual among malignancies, with inflammation playing such a prominent role in its pathogenesis. S100A8/A9 (calprotectin) is a heterodimeric protein, which has a role in the inflammatory response and oncogenesis. In this study in HL patients, the correlation between serum S100A8/A9 levels and treatment responses was investigated along with whether this marker is correlated with other inflammatory markers. MATERIALS AND METHODS: Thirty-three HL patients and 20 healthy volunteers were included. Demographic and clinical characteristics were recorded. Calprotectin levels were measured with Human S100A8/A9 Heterodimer Quantikine ELISA kit. Calprotectin levels were measured twice in patients, before and after treatment, and once in the control group. Treatment responses were evaluated with positron emission tomography-computed tomography (PET-CT). RESULTS: The mean age of patients was 44.3 ± 18.1 (66.3% male). The median (IQR) values of S100A8/A9 before and after treatment in the patient group were 4.98 (2.6-7.8) and 1.87 (1.1-4.8)µg/mL. Median (IQR) S100A8/A9 concentration in the control group was 1.41 (0.98-2.73)µg/mL. In patients, pretreatment values were significantly higher than in controls (P < .001). However, median values of patients after treatment and controls were similar. Patient median S100A8/A9 levels were significantly lower post-treatment compared with pretreatment values (P = .001). When inflammatory markers were examined within groups, no relationship was found between markers. In ROC analysis, a S100A8/A9 cutoff value of ≥3.31µg/mL accurately discriminated end-of-treatment PET positivity (AUC = 0.78; 95% CI 0.58-0.98; accuracy = 76.2%). CONCLUSION: S100A8/A9 may be a potential biomarker for treatment response in HL independent of inflammation. This is the first study to investigate and show this finding. However, further large-scale studies are still required.

Factors affecting inadequate response to HBV vaccine in hemodialysis patients: northeast anatolia survey with six hemodialysis centers.

BACKGROUND: In hemodialysis patients Hepatitis B virus (HBV) infection is one of the problems. Because of HBV vaccine response is lower than in the general population, in this study it is aimed to determine the factors that may cause inadequate HBV vaccine response in hemodialysis patients. METHODS: In study, HBsAg, anti-HBs, anti-HBc IgG data belonging to 278 patients were obtained from file and computer records. It was seen that seronegative cases had been given recombinant HBV vaccine. Anti-HBs titers were monitored 1 month after vaccination was completed. According to this, the patients are divided into two groups. Those with anti-HBs < 10 IU/mL were identified as non-responders and with anti-HBs ≥ 10 IU/mL as responders. Factors such as age, serum albumin and urea reduction rate which may affect inadequate response to HBV vaccine were evaluated. As statistical examination, Chi-square test was used for the analysis of the data determined by counting, and logistic regression was used for statistically significant independent variables in chi-square test. p value of < 0.05 was considered statistically significant (Confidence interval: 95%). RESULTS: Out of 278 patients, according to exclusion criteria 81 patients were excluded. 13.2%(26/197) of HBV vaccinated patients had insufficient response. The inadequate response rate to HBV vaccination was found to be higher in patients with age ≥ 65 (p = 0.039), serum albumin < 3.5 g/dL (p = 0.024) and urea reduction rate ≤ 65 (p = 0.028). No statistically significant relationship was found between inadequate response to HBV vaccine and anti-HCV positivity, presence of diabetes mellitus, anemia status, vitamin D therapy and vascular access pathway variability. CONCLUSION: We conclude that relatively high patient age, low albumin level and insufficient urea reduction rate may cause inadequate HBV vaccine response. Taking these factors into consideration may provide a useful insight for an adequate response to vaccination.

IPSET-Thrombosis Better Identifies Thrombosis-Free Survival: A Turkish Cohort.

INTRODUCTION: Essential thrombocythemia (ET) is the most common of the myeloproliferative neoplasms. For better predicting the occurrence of thrombotic events, an International Prognostic Score of Thrombosis for ET (IPSET-Thrombosis) was recently developed. We aimed to investigate the validity of IPSET-Thrombosis in a Turkish patient cohort and to compare the efficacy of IPSET-Thrombosis and conventional risk scoring systems in predicting thrombosis-free survival. PATIENTS AND METHODS: We retrospectively evaluated the clinical characteristics and risk factors for thrombosis in 112 Turkish patients. Median thrombosis-free survival and Harrell C concordance indexes were calculated for both conventional and IPSET-Thrombosis. RESULTS: Median age of 112 patients included in the study was 61 (range, 27-90) years at the time of diagnosis. When patients were stratified according to the conventional risk stratification system, 43.8% of patients were in the low-risk group and 56.2% in the high-risk group. A total of 22.4% of low-risk and 42.9% of high-risk patients had at least one thromboembolic event. When patients were stratified according to the IPSET-Thrombosis, 33% were in the low-risk group, 26.8% in the intermediate-risk group, and 40.2% in the high-risk group. Considering IPSET-Thrombosis risk groups, 5.4% of low-risk, 26.7% of intermediate-risk, and 66.2% of high-risk patients had at least one thromboembolic event. Regarding IPSET-Thrombosis risk groups, 10-year thrombosis-free survival was 86.8% for low-risk, 39.4% for intermediate-risk, and 32.9% for high-risk groups (P < .001). Harrell C concordance indexes of conventional and IPSET-Thrombosis were 0.60 and 0.77, respectively. CONCLUSION: By validating the reproducibility of IPSET-Thrombosis in Turkish ET patients, we found that IPSET-Thrombosis identifies thrombosis-free survival better than the conventional risk stratification system.