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.

A safety review of tyrosine kinase inhibitors for chronic myeloid leukemia.

INTRODUCTION: Since the introduction of first tyrosine kinase inhibitor (TKI) imatinib, the treatment of chronic myeloid leukemia (CML) has reached excellent survival expectancies. Long survival rates bring about issues regarding TKI safety. AREAS COVERED: The aim of this review is to compare the side effects of current TKIs both in the first and later lines and outline a safety andprofile of CML treatment. Seminal studies on TKIs and other newer drugs and extended follow-up of these studies; real-life data of each drug were usedduring the course of this. PubMed was used as a search database and onlyarticles in English were included. EXPERT OPINION: With longer follow-up CML patients, resistant slowgrade adverse events seem to be the major obstacle in the way of treatmentefficacy. If efficacy is the priority, vigorous treatment of side effect and administration of full dose TKI are reasonable. But when treatment goals are reached, dose modifications or alternative treatment regimens may be acceptedpossible. More studies are needed on dose modification protocols and potential benefits and safety of treatment-free remission.

Does discontinuing bleomycin due to toxicity increase the risk of lymphoma progression? Real-life data from a homogeneous population of advanced stage Hodgkin lymphoma.

Hodgkin Lymphoma (HL) is often curable with ABVD therapy and improving outcomes is a main goal of ongoing research. Bleomycin-associated pneumonitis (BAPT) is a potentially life-threatening complication that necessitates bleomycin discontinuation. We conducted this study on a homogenous cohort of advanced stage HL treated only with ABVD for frontline therapy to assess if bleomycin discontinuation increases the risk of lymphoma progression. After the exclusion of patients who received radiotherapy or other drugs, 106 and 28 patients in the six-cycle ABVD and BAPT groups respectively had similar survival curves for progression and death with a 49-month median follow-up. PFS rates were also very similar at two and four years from diagnosis with 2-year PFS rates of 83.9% and 82.1% (RR = 1.1 95%CI = 0.45-2.2). Outcome comparisons were also similar between the two groups when stratified according to early response assessment with PET/CT. Patients who discontinued bleomycin due to toxicity did not experience an increased risk of progression compared to patients who completed six ABVD cycles.

Efficacy and Safety of Imatinib Treatment in Elderly Patients With Chronic Myeloid Leukemia: Real-Life Data and a Single-Center Experience.

BACKGROUND: In the era of tyrosine kinase inhibitors (TKIs), chronic myeloid leukemia (CML) patients generally live close to a normal lifespan, and the number of elderly patients with CML with comorbidities is increasing. PATIENTS AND METHODS: We retrospectively compared the efficacy and safety of frontline imatinib between elderly patients (≥60 years old) and younger patients (<60 years old) with CML. RESULTS: The study included 33 elderly and 125 younger patients. Elderly patients had significantly higher Charlson comorbidity index (CCI) scores. Efficacy and toxicity were comparable among the older patients with CCI scores of 0 and ≥1. There were significantly more hematologic adverse events (AEs) in elderly patients (P = .005). Although not significant, nonhematologic AEs were also more common in older cases (P = .056). Elderly patients had significantly higher rates of imatinib dose reduction (P < .001). Cumulative response rates were similar in both groups. Event-free survival was comparable, and overall survival (OS)-when non-CML-related deaths were censored-was also similar. In the multivariate analysis, age at diagnosis and CCI were associated with OS, and patients ≥ 60 years of age had a 5.998-times higher risk of death compared with the patients < 60 years of age (P = .011). Similarly, patients with CCI scores ≥ 2 had a 3.758-times higher risk of death compared with patients with a CCI score of 0 (P = .033). CONCLUSIONS: Upfront imatinib was generally well tolerated among elderly Turkish patients with CML with non-inferior responses and long-term outcomes when compared with younger patients. Comorbidities can be problematic in elderly patients, and today the survival of patients with CML is determined mostly by comorbidities.