The assessment of health-related quality of life in patients with polycythemia vera.

Previous studies have shown that patients with polycythemia vera (PV) have poor quality of life (QoL). Similarly, it has been shown that survival is influenced by QoL. We aimed to evaluate QoL in 88 Turkish patients with PV. This cross-sectional study included cases diagnosed with PV between January 1995 and August 2019 who attended follow-up studies in the hematology department of a tertiary hospital in Türkiye between August 2019 and July 2020. Beginning in August 2019, subjects who approved study participation applied the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) questionnaire during their routine follow-up-given that they met inclusion/exclusion criteria. Individuals with comorbidities or factors influencing QoL and those with secondary PV-related conditions were excluded. Recorded data included age, sex, history of bleeding, thrombosis, erythrocytosis, leukocytosis, thrombocytosis, obesity or splenomegaly, and cytogenetic mutation profiles such as JAK2, BCR and MPL. We also assessed whether they needed phlebotomy or erythrocyte suspensions. Data concerning comorbidities and medication use were obtained from medical records. The median age of patients was 52 (44-61) years. The majority of participants were male (67.05%). Global health status score was 75 (66.67-83.33). PV patients who had required phlebotomy demonstrated higher social functioning scores (P = .004) and lower scores for loss of appetite (P = .013) and financial difficulties (P = .020) than patients without phlebotomy. PV patients who had suffered from leukocytosis demonstrated lower physical functioning scores compared to those without leukocytosis (P = .001). Patients without JAK2 exon 14 mutations had better physical (P = .016) and cognitive functioning scores (P = .048). It was found that PV patients with splenomegaly demonstrated lower physical functioning (P = .019) and higher appetite loss scores (P = .005) than those without splenomegaly. Higher leucocyte counts were associated with decreased physical functioning and greater fatigue. In conclusion, we demonstrated deterioration of physical and emotional QoL in patients diagnosed with PV. Patients with PV require individualized, patient-specific and integrated approaches in order to minimize symptoms, improve QoL, and increase survival.

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.

Complex karyotype with double Philadelphia chromosome and T315I mutation results in blastic phase and extensive extramedullary infiltration in a chronic myeloid leukemia patient.

Chronic myeloid leukemia (CML) is a common hematological malignancy originating from bone marrow stem cells. Chromosomal abnormalities can be seen in almost all cases, the most known anomaly being Philadelphia (Ph) chromosome, a derivative chromosome resulting from a translocation between 9. and 22. chromosome. Other chromosomal abnormalities may be present in 10% of patients at diagnosis, although they emerge frequently during the acute transformation and can be associated with unfavorable significance. Also, point mutations like T315I in BCR-ABL fusion gene may arise during the course of the disease and thereby cause tyrosine kinase inhibitors (TKI) resistance. Here, we report a BCR-ABL positive CML patient who was followed for 6 years in major molecular response (MMR), complete cytogenetic response (CCR), and complete hematological response (CHR). He had a sudden loss of hematological, cytogenetic, and molecular response with a very aggressive blastic course and extensive extramedullary infiltration, with T315I mutation, complex translocations, an extra Ph chromosome, and additional chromosomes. The patient who received intensive cytotoxic chemotherapy together with ponatinib treatment, which is effective for the T315I mutation, never went into remission, and there was no chance of transplantation because a suitable donor for HLA could not be found. Although these findings are not very rare individually, coexistence of complex karyotype and T315I mutation is not frequent and complicates clinical management. Our patient is the first case in literature with all disclosed findings together and indicates the importance of early detection of these chromosomal and molecular abnormalities.

The Real-World Experience With Single Agent Ibrutinib in Relapsed/Refractory CLL.

INTRODUCTION/BACKGROUND: The emergence of novel agents targeting the B-cell receptor pathway and BCL-2 has significantly changed the therapeutic landscape of CLL. We evaluated the safety and efficacy of single-agent ibrutinib in relapsed/refractory CLL in real-world settings. PATIENTS/METHODS: A total of 200 relapsed/refractory CLL patients with a median age of 68 were included in this retrospective, multicenter, non-interventional study. Data of the study were captured from the patient charts of the participating centers. RESULTS: The median for lines of previous chemotherapy was 2 (1-6); 62 (31.8%) patients had del17p and/or p53 mutations (del17p+/p53mut). Of the study group, 146 (75%) patients achieved at least PR, while 16 (8.7%) patients discontinued ibrutinib due to TEA. The most common drug-related adverse events were neutropenia (n: 31; 17.4%) and thrombocytopenia (n: 40; 22.3%), which were ≥ grade 3 in 9 (5%) and 5 (3.9%) patients, respectively. Pneumonia (n: 42; 23.7%) was the most common nonhematologic TEA. Atrial fibrillation (n: 5; 2.8%) and bleeding (n: 11; 6.3%) were relatively rare during the study period. Within a median follow-up period of 17 (1-74) months, 42 (21%) patients died. The estimated median OS of the study cohort was 52 months. Only the response to ibrutinib (CR/PR vs. SD/PD) was significantly associated with OS. CONCLUSION: Our results indicate good safety and efficacy for single-agent ibrutinib in R/R CLL in daily practice.

Efficacy and Safety of Ibrutinib Therapy in Patients with Chronic Lymphocytic Leukemia: Retrospective Analysis of Real-Life Data

Objective: This study aimed to retrospectively evaluate the efficacy, safety, and survival outcome of single-agent ibrutinib therapy in chronic lymphocytic leukemia patients. Materials and Methods: A total of 136 patients (mean age ± standard deviation: 64.6±10.3 years, 66.9% males) who had received at least one dose of ibrutinib were included in this retrospective multicenter, noninterventional hospital-registry study conducted at 33 centers across Turkey. Data on patient demographics, baseline characteristics, laboratory findings, and leukemia-cell cytogenetics were retrieved. Treatment response, survival outcome including overall survival (OS) and progression-free survival (PFS), and safety data were analyzed. Results: Overall, 36.7% of patients were categorized as Eastern Cooperative Oncology Group (ECOG) class 2-3, while 44.9% were in Rai stage 4. Fluorescence in situ hybridization revealed the presence of del(17p) in 39.8% of the patients. Patients received a median of 2.0 (range: 0-7) lines of pre-ibrutinib therapy. Median duration of therapy was 8.8 months (range: 0.4-58.0 months). The 1-year PFS and OS rates were 82.2% and 84.6%, respectively, while median PFS time was 30.0 (standard error, 95% confidence interval: 5.1, 20.0-40.0) months and median OS time was 37.9 (3.2, 31.5-44.2) months. Treatment response (complete or partial response), PFS time, and OS time were better with 0-2 lines versus 3-7 lines of prior therapy (p<0.001, p=0.001, and p<0.001, respectively), with ECOG class 0-1 versus class 2-3 (p=0.006, p=0.011, and p=0.001, respectively), and with Rai stage 0-2 versus 3-4 (p=0.002, p=0.001, and p=0.002, respectively). No significant difference was noted in treatment response rates or survival outcome with respect to the presence of comorbidity, bulky disease, or del(17p). While 176 adverse events (AEs) were reported in 74 (54.4%) patients, 46 of those 176 AEs were grade 3-4, including pneumonia (n=12), neutropenia (n=11), anemia (n=5), thrombocytopenia (n=5), and fever (n=5). Conclusion: This real-life analysis confirms the favorable efficacy and safety profile of long-term ibrutinib treatment while emphasizing the potential adverse impacts of poorer ECOG performance status, heavy treatment prior to ibrutinib, and advanced Rai stage on patient compliance, treatment response, and survival outcomes.