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.

Guidelines for the treatment of chronic myeloid leukemia from the NCCN and ELN: differences and similarities.

Patients diagnosed with chronic myeloid leukemia (CML) in chronic phase can now have a life expectancy comparable to that of the general population thanks to the use of tyrosine kinase inhibitor (TKI) therapies. Although most patients with CML require lifelong TKI therapy, it is possible for some patients to achieve treatment-free remission. These spectacular results have been made possible by the development of superior treatment modalities as well as clinicians' efforts in strictly adhering to clinical guidelines such as the National Comprehensive Cancer Network (NCCN) and European Leukemia Network (ELN). CML treatment recommendations reported in these guidelines are the result of years of selecting and incorporating the most reliable evidence. In this review, we provide a synopsis of the differences and similarities that exist between the NCCN and ELN guidelines.

Leukemic stem cells shall be searched in the bone marrow before "tyrosine kinase inhibitor-discontinuation" in chronic myeloid leukemia.

BACKGROUND: Leukemic stem cells (LSCs) of chronic myeloid leukemia (CML), persisting in the bone marrow (BM) niche, could be responsible for the relapses within the patients of whom the treatment-free remission (TFR) had been attempted. We assessed the presence of the CML LSCs in the peripheral blood (PB) and concurrently in the BM in the patients with chronic-phase CML (CP CML). PATIENTS AND METHODS: Thirty-eight patients with CP CML were included into the study. CD45+ /CD34+ /CD38- cells with positive CD26 expression were considered as CML LSCs (CD26+ LSC) by using multiparameter flow cytometry (FCM). RESULTS: Mean BCR-ABL, PB LSC, and BM LSC were 58.528 IS (37.405-83.414 IS), 237.5 LSC/µL (16-737.5 LSC/µL), and 805 LSC/106  WBCs (134.6-2470 LSC/106  WBCs), respectively, in newly diagnosed CML patients. In the patients with BCR-ABL positive hematopoiesis, mean BCR-ABL, PB LSCs, and BM LSCs were 30.09 IS (0.024-147.690 IS), 13.5 LSC/µL (0-248.7 LSC/µL) and 143.5 LSC/106  WBCs (9-455.2 LSC/106  WBCs), respectively. No CML LSCs were detected in PB of patients who achieved deep molecular response (DMR). BM LSCs of the patients who were in DMR were 281.1 LSC/106  WBCs (3.1-613.7 LSC/106  WBCs). The amount of PB LSCs was highest in patients with newly diagnosed CML (P < .001). CONCLUSION: LSCs persisted in the BM of the patients with DMR, whereas there was no LSCs in the peripheral blood. The investigation of the CML LSCs in bone marrow before deciding TKI discontinuation could be justified to achieve and maintain stable TFR.

Blastic Plasmacytoid Dendritic Cell Neoplasm: Single Center Experience on a Rare Hematological Malignancy.

PURPOSE: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and poor prognostic hematological malignancy. There is still no standard treatment established for BPDCN patients. We aim to summarize the main clinical, biological features and treatment of 9 BPDCN patients. METHODS: Nine patients with BPDCN who had been diagnosed between July 2008 and December 2018 in Ankara University School of Medicine, were retrospectively evaluated. RESULTS: All patients (n = 9) were male, median age was 64 (21-80). Five patients (55.6%) had bone marrow infiltration, 5 patients (55.6%) cutaneous lesions, 6 patients (66.7%) lymph node involvement, 2 patients (22.2%) central nervous system involvement and 2 patients (22.2%) spleen involvement at time of diagnosis. Complex karyotype was observed in 2 patients. CHOP was given to 5 patients (55.6%), hyper-CVAD to 2 patients (22.2%), fludarabine, cyclophosphamide and mitoxantrone to 1 patient (11.1%) and cyclophosphamide, etoposide, methylprednisolone to 1 patient (11.1%) as first line chemotherapy. Four patients (44.4%) underwent allogeneic hematopoietic stem cell transplantation (AHSCT) in complete remission (CR) 1. Venetoclax was given to a transplant ineligible patient who had skin and lymph node involvement, with the off-label use. The median follow-up time was 15.9 months (3-48.6 months). Estimated median overall survival was 15.9 + 1.6 (95% CI 12.7-19.1) months. CONCLUSION: Intensive induction therapies followed by AHSCT in CR seems to be best approaches for patients with BPDCN. Thus, more effective treatment strategies particularly targeted therapies should be warranted to improve the survival of patients with this rare disease.

Highlighting the Prognostic Importance of Measurable Residual Disease Among Acute Myeloid Leukemia Risk Factors

Objective: The optimal timing of measurable residual disease (MRD) evaluation in acute myeloid leukemia (AML) patients has not been well defined yet. We aimed to investigate the impact of MRD in pre- and post-allogeneic hematopoietic stem cell transplantation (AHSCT) periods on prognostic parameters. Materials and Methods: Seventy-seven AML patients who underwent AHSCT in complete morphological remission were included. MRD analyses were performed by 10-color MFC and 10-4 was defined as positive. Relapse risk and survival outcomes were assessed based on pre- and post-AHSCT MRD positivity. Results: The median age of the patients was 46 (range: 18-71) years, and 41 (53.2%) were male while 36 (46.8%) were female. The median follow-up after AHSCT was 12.2 months (range: 0.2-73.0). The 2-year overall survival (OS) in the entire cohort was 37.0%, with a significant difference between patients who were MRD-negative and MRD-positive before AHSCT, estimated as 63.0% versus 16.0%, respectively (p=0.005). MRD positivity at +28 days after AHSCT was also associated with significantly inferior 2-year OS when compared to MRD negativity (p=0.03). The risk of relapse at 1 year was 2.4 times higher (95% confidence interval: 1.1-5.6; p=0.04) in the pre-AHSCT MRD-positive group when compared to the MRD-negative group regardless of other transplant-related factors, including pre-AHSCT disease status (i.e., complete remission 1 and 2). Event-free survival (EFS) was significantly shorter in patients who were pre-AHSCT MRD-positive (p=0.016). Post-AHSCT MRD positivity was also related to an increased relapse risk. OS and EFS were significantly inferior among MRD-positive patients at +28 days after AHSCT (p=0.03 and p=0.019). Conclusion: Our results indicate the importance of MRD before and after AHSCT independently of other factors.

A Case of Superwarfarin Poisoning Due to Repetitive Occupational Dermal Rodenticide Exposure in a Worker.

Superwarfarin poisoning is usually due to chronic occult small-dose exposures and can easily be misdiagnosed and may lead to serious complications. The diagnosis can be confirmed by a concordant history and analyses of blood and urine specimens with the liquid chromatography with tandem mass spectrometry (LC-MS/MS) technique. Several months of continuous treatment with high doses of daily oral vitamin K, as well as other supportive measures, are warranted, especially when repeated laboratory measurements to help predict the treatment period are not available. In this paper, a case of superwarfarin poisoning due to chronic repetitive occupational dermal exposure to commercial rodenticides is presented.