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 Turkiye 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.

JAK inhibitors (JAKis), used in the treatment of myelofibrosis, have entered standard treatment, providing significant improvements in spleen size and symptom burden. Although splenomegaly provides a reduction and some improvement in cytopenia, there is still a way to go. Novel JAKis are being investigated to overcome barriers to treatment access, such as therapeutic challenges, intolerance, and unresponsiveness. This review includes the current status of JAKi treatment for myelofibrosis, mainly focusing on investigational JAKis; jaktinib, lestaurtinib, itacitinib, gandotinib, BMS-911543, ilginatinib, TQ05105, and flonoltinib maleate. MEDLINE and clinicaltrials.gov were screened to identify all completed or active studies on this topic. The outcomes of the preclinical studies and clinical trials are presented and discussed for each drug. In patients with myelofibrosis, momelotinib was effective in treating anemia, whereas jaktinib was effective in both anemia and Total Symptom Score (TSS). More phase 3 studies are needed to provide more precise evidence. The increasing variety of JAKis will allow for more personalized treatment options for myelofibrosis in the future. The potential impact on disease progression, molecular responses, and the duration of this response will become important parameters for future evaluations of these drugs.

Objectives: Patients with hematologic malignancies have a high risk of coronavirus disease 2019 (COVID-19) mortality. This study aimed to investigate the impact of COVID-19 on mortality rates in patients with various hematologic malignancies and to determine risk factors associated with all-cause mortality. Methods: A multi-center, observational retrospective analysis of patients with hematologic malignancies infected with COVID-19 between July 2020 and December 2021 was performed. Demographic data, clinical characteristics, and laboratory parameters were recorded. Patients were grouped as non-survivors and survivors. All-cause mortality was the primary outcome of the study. Results: There were 569 patients with a median age of 59 years. Non-Hodgkin lymphoma (22.0%) and multiple myelomas (18.1%) were the two most frequent hematologic malignancies. The all-cause mortality rate was 29.3%. The highest mortality rates were seen in patients with acute myeloid leukemia (44.3%), acute lymphoid leukemia (40.5%), and non-Hodgkin lymphoma (36.8%). The non-survivors were significantly older (p<0.001) and had more comorbidities (p<0.05). There were significantly more patients with low lymphocyte percentage (p<0.001), thrombocytopenia (p<0.001), and high CRP (p<0.001) in the non-survived patients. Cardiac comorbidities, (p=0.016), cytotoxic chemotherapy (p=0.024), low lymphocyte percentage (p=0.025), thrombocytopenia (p<0.0001), and high CRP values (p=0.017) were the independent risk factors for the prediction of mortality. Conclusions: In patients with hematologic malignancies, coexistent COVID-19 leads to a higher mortality rate in elderly patients with more comorbidities. Acute myeloid and lymphoid leukemia and non-Hodgkin lymphoma have the highest mortality rates. Cardiac diseases, cytotoxic chemotherapy, lymphopenia, thrombocytopenia, and high CRP are the independent risk factors for mortality in hematologic malignancy patients with COVID-19. Keywords: Covid; Hematologic Malignancy; Cytotoxic chemotherapy.

In recent years, new developments have been incorporated into daily practice in the management of immune thrombotic thrombocytopenic purpura (iTTP). In particular, clinical scoring systems could help clinicians with clinical decision-making and early recognition. However, older patients frequently present with more organ involvement and in unusual ways. The ways in which age could affect these clinical prediction scoring systems remain unclear. We evaluated the use of PLASMIC and French scores in patients over 60 years of age. We performed a retrospective cross-sectional analysis of patients over 60 years of age with a presumptive diagnosis of iTTP between 2014 and 2022 at 10 centers. We calculated PLASMIC and French scores and compared our data with a single-center analysis of younger patients presenting with thrombotic microangiopathy. Our study included 30 patients over 60 years of age and a control group of 28 patients younger than 60 years. The diagnostic sensitivity and specificity of a French score of ≥1 were lower in older patients compared to the control group (78.9% vs. 100% and 18.2% vs. 57.1%, respectively). The diagnostic sensitivity and specificity of a PLASMIC score of ≥5 were 100% vs. 95% and 27.3% vs. 100% for the study group and control group, respectively. Our study showed a higher mortality rate in older patients compared to the control group (30% vs. 7.1%, p=0.043). For a limited number of patients (n=6), our results showed that rituximab can reduce mortality. Given that the reliability of clinical prediction scores for iTTP in older patients may be lower, more caution must be undertaken in interpreting their results.

The study aims to investigate second primary malignancy (SPM) development and frailty in Turkish geriatric patients with multiple myeloma (MM) and to assess the relationship between overall survival (OS) and various characteristics including SPM and frailty. Seventy-two patients diagnosed with and treated for MM were enrolled in the study. Frailty was determined by the IMWG Frailty Score. Fifty-three participants (73.6%) were found to have clinically-relevant frailty. Seven patients (9.7%) had SPM. Median follow-up was 36.5 (22–48.5) months, and 17 patients died during the follow-up period. Overall (OS) was 49.40 (45.01–53.80) months. Shorter OS was found in patients with SPM (35.29 (19.66–50.91) months) compared to those without (51.05 (46.7–55.4) months) (Kaplan–Meier; p = 0.018). The multivariate cox proportional hazards model revealed that patients with SPM had 4.420-fold higher risk of death than those without (HR: 4.420, 95% CI: 1.371–14.246, p = 0.013). Higher ALT levels were also independently associated with mortality (p = 0.038). The prevalence of SPM and frailty was high in elderly patients with MM in our study. The development of SPM independently reduces survival in MM; however, frailty was not found to be independently associated with survival. Our results suggest the importance of individualized approaches in the management of patients with MM, particularly with regard to SPM development.

Background/Aim: Rapid identification of patients with myeloproliferative neoplasms (MPNs) is crucial for clinical decision-making and healthcare management. Sarcopenia is characterized by muscle loss and increases the risks for adverse outcomes; there is limited information in the literature regarding possible links between sarcopenia and MPNs. This study evaluated the frequency of sarcopenia in patients with MPNs and investigated whether biochemical or clinical features were associated with the development of sarcopenia. Methods: Fifty-six BCR-ABL1-negative patients were included in this randomized prospective cohort research study. Muscle strength was measured using a handgrip dynamometer. Muscle mass was evaluated using a bioelectrical-impedance analyzer, and physical performance was evaluated via gait speed in a 6-minute walking test. Results: The mean handgrip strength of the cohort was 27.7 kg, and 13 patients (23.2%) tested positive for low muscle strength. Mean muscle mass was found to be 7.58 (1.17) kg/m2, and seven patients (12.5%) exhibited low muscle mass. Three patients (5.4%) had low muscle quality. Nine patients (16.1%) were diagnosed with probable sarcopenia, and four patients (7.1%) were diagnosed with severe sarcopenia. There was no difference between the groups in terms of clinical features (P>0.05), nutritional assessment (macro and micronutrients) (P=0.959), comorbidities (P=0.476), or laboratory measurements (P>0.05). Conclusion: There was a high prevalence of sarcopenia among patients with MPNs, which indicates that periodic measurements of muscle strength, body composition and physical performance may contribute to the management of MPNs.