Tailored tyrosine kinase inhibitor (TKI) treatment of chronic myeloid leukemia (CML) based on current evidence

Philadelphia (Ph*)/BCR-ABL1-positive chronic myeloid leukemia (CML) is a neoplastic hematologic disorder, which is a functionally curable chronic disease via using tyrosine kinase inhibitor (TKI) drugs. The life expectancy for the vast majority of chronic phase-CML patients is "normal", thanks to the unique effectiveness of the ABL-targeted TKIs of CML. The patients with CML receiving TKI could be expected to have a survival and 'quality of life' of the age- and sex-matched healthy people. Several TKI pathways may be selected for the first line CML treatment, including first-generation original/generic imatinib or second-generation TKIs, such as bosutinib, nilotinib, and dasatinib. Individual characteristics of the CML patients, TKI drug compliance, lifestyle preferences, comorbidities, distinct toxicity profile of the TKI drug, and physician-clinical center experience are among the critical factors to be taken into account while deciding on the proper first line TKI in the newly diagnosed CML patients. Identifying CML patients at a higher risk for the disease progression or TKI resistance is essential and could influence the choice of primary TKI. The optimized integrations of the best available evidence, individual patient characteristics, and physician clinical experience are required in order to select best TKI for the CML management. Pathobiological basis depending upon the prospective in vivo research data is also crucial during the follow-up as well

Covid-19 scientific publications from Turkey

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) outbreak poses a major global threat to the public health worldwide. The infectious disease caused by the virus that affected the entire world was named as the Coronavirus disease-2019 (COVID-19). The knowledge regarding the wide clinico-biological aspects of the COVID-19 continues to evolve very rapidly, given the growing data from all over the world. During this complicated process, healthcare professionals have benefited from each other's experiences in combatting against the COVID-19 syndrome. COVID-19 related studies have been performed by a wide variety of research groups in Turkey as well as the rest of the world. The aim of this paper is to outline Turkish COVID-19 research indexed in the LitCovid system. LitCovid is a curated literature hub for tracking up-to-date scientific data about the SARS-CoV-2. COVID-19's first case was detected in Turkey, on March 11th, 2020. Six months after the first case was observed, the total number of COVID-19 patients was reported to be as 286,455, and the total number of deaths due to SARS-CoV-2 was 6895. The genetic sequence of the novel coronavirus showed significant identity to SARS-CoV and MERS-CoV. Numerous drugs including lopinavir/ritonavir, favipiravir, neuraminidase inhibitors, remdesivir, umifenovir, azithromycin, and chloroquine have been suggested for the management of COVID-19 although the exact treatment is yet to be determined

Comment on Zamfir et al. Hematologic Malignancies Diagnosed in the Context of the mRNA COVID-19 Vaccination Campaign: A Report of Two Cases. Medicina 2022, 58, 874

The SARS-CoV-2 spike protein mRNA-based vaccines have prevented countless mortality and morbidity, and have an excellent risk/benefit ratio. However, various adverse events may rarely occur after the BNT162b2 vaccine, like any other medical intervention. The COVID-19 itself and the spike protein produced endogenously by mRNA vaccines may have immunological, microenvironmental, prothrombotic, and neoplastic effects. As a contribution to the published report, we would like to share our experience regarding four cases in which myeloid neoplasms emerged following the vaccination. Conclusions: There is no doubt that vaccination could continue along the lines of established universal recommendations. Meanwhile, all hematological adverse events must be closely monitored and reported. Further efforts should be focused on the probable pathobiological mechanisms and causalities of spike protein-related toxicity and clonal myeloid disorders

The Impact Of Jak/Stat Inhibitor Ruxolitinib On The Genesis Of Lymphoproliferative Diseases

Background/aim Ruxolitinib, a JAK/STAT signaling pathway inhibitor targeted drug, has been approved for the controlling of disease symptoms and splenomegaly in patients with myeloproliferative neoplastic diseases. Recently, it has been proposed that ruxolitinib-induced JAK/STAT pathway inhibition in myelofibrosis is associated with an elevated frequency of aggressive B-cell lymphomas. However, the biological basis and significance of this pharmacobiological adverse event is unknown. The aim of this bioinformatics study is to detect any possible confounding effects of ruxolitinib on the genesis of lymphoproliferative disorders. Materials and methods The gene expression data were retrieved from the E-MTAB-783 Cancer Genome Project database. Gene expression data for all available genes in 26 cell lines belonging to various types of lymphomas were chosen for use in this in silico analysis. Results We identified genes that were significant in developing resistance to ruxolitinib in lymphoma cell lines. Conclusion Based on the results of our present study, ruxolitinib may potentially lead to the pathological expression of the transcription factors important in lymphoma genesis, neoplastic commitment on the progenitor lymphoid cells, inhibition of repressor transcriptions protective for lymphoma development, inhibition of apoptosis, promotion of neoplastic proliferation, transcriptional activation, and proliferation of malignant neoplastic B cells.PubMedWoSScopu

Unclassifiable non-CML classical myeloproliferative diseases with microcytosis

Background/aim Polycythemia Vera (PV) is a myeloproliferative disorder characterized by overproduction of morphologically normal red blood cells (RBCs), granulocytes, and platelets, a phenotype that is caused by a mutation (V617F) in Janus kinase 2 (JAK2). However, JAK2 V617F is also found in approximately 50% of patients with essential thrombocytosis and primary myelofibrosis, rendering its presence nonspecific as a diagnostic test. An increased red cell mass is a major criterion for the diagnosis of PV according to World Health Organization (WHO) 2016 criteria. High hemoglobin (Hgb) or Hematocrit (Hct) are universally used as indicators of an increased red cell mass for the diagnosis of PV. However, conditions such as iron deficiency (ID) with decreased mean cell volume may mask the diagnosis due to nonelevated Hct level. The aim of this study was to investigate the clinical characteristics of the patients with unclassifiable non-CML classical myeloproliferative disease with microcytosis (MPD/M) and nonelevated Hgb and Hct levels at diagnosis and to determine if some of these cases could be real PV cases masked due to ID-related microcytosis. Materials and methods There were 23 MPD/M cases among 208 non-CML classical MPD cases (11%). Among 22 patients who had adequate test results related to the cause of microcytosis, ID and beta-thalassemia trait (TT) were the apparent causes of microcytosis in 15 and 1 cases, respectively. Results Clinicopathological correlations revealed consistently positive JAK2 V617F mutation status (20/20, 100%), frequently elevated RBC count (17/23, 73.9%), and PV-compatible bone marrow findings (10/12, 83.3%). These findings are compatible with PV instead of essential thrombocytopenia or primary myelofibrosis. In spite of frequent cytoreductive treatment, 3 patients developed increased Hgb/Htc levels during median 58.2 (279–63) months’ follow-up. Conclusion These data show that the majority of MPD/M cases are PV patients masked due to ID-related microcytosis.PubMedWoSScopu

Oral High-Dose Ankaferd Administration Effects On Gastrointestinal System

Background and aims: Ankaferd Blood Stopper (ABS) is a herbal extract obtained from five different plants. It has a therapeutic potential for the management of external hemorrhage and controlling gastrointestinal bleeding. However, ABS's effects are not unknown on gastrointestinal systems. The aim of this study was to assess the effect of short- and long-term systemic exposure and gastrointestinal safety following the oral administration of high-dose ABS in rats., Methods: Eighteen healthy adult male rats were included into the study. The rats were divided into 4 groups: group A was fed with high dose ABS (2ml/Kg) for one week, group B for one month, group C for three months and group D's diet did not contain any ABS. On termination of the ABS treatment, the gastrointestinal system from the esophagus to the anus and the liver were surgically removed and histological investigated., Results: During the study period, there was no mortality; signs of intoxication in any of the studied groups. No gastrointestinal tissue fibrosis, dysplasia, or metaplasia was detectable in any of the groups. The stomach had a normal morphology in all groups. However, the other gastrointestinal tract sections showed mucosal inflammation, goblet cell decrements, and intra-epithelial lymphocyte infiltration. The most common changes were mucosal inflammation in all rats in group B and C. Frequency of inflammation was greater in groups B and C in comparison to group A (P= 0.001). Loss of goblet cell and intra-epithelial lymphocyte infiltration were not significantly different between groups A and B (P=0.308 and P=0.189, respectively). However, there was significantly higher intra-epithelial lymphocyte infiltration in group C than in group A (P=0.04). Histopathological examination of the liver showed no inflammation, fibrosis, bile duct destruction or proliferation in any of the groups. However, each groups revealed vascular dilatation and erythrocyte accumulation at the sinusoidal structures of the liver., Conclusions: ABS seems to be a safe agent and it can be used for hemorrhage originated from gastric lesions. Further work needs to be done to establish whether ABS leads to be used to stop gastrointestinal bleeding.PubMedWoSScopu

Mitoxantrone-Melphalan Conditioning Regimen For Autologous Stem Cell Transplantation In Relapsed/Refractory Lymphoma

Background/aim High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) has become the standard approach for patients with relapsed/refractory Hodgkin’s lymphoma (HL) or non-Hodgkin’s lymphoma (NHL). In this study, we report the outcome of the mitoxantrone-melphalan conditioning regimen for lymphoma. Materials and methods The study group included 53 patients who were relapsed/refractory HL (n = 14) and NHL (n = 39) and received mitoxantrone and melphalan followed by ASCT. The transplant regimen consisted of mitoxantrone (60 mg/m2) and melphalan (180 mg/m2) followed by peripheral blood stem cell infusion (PBSC). Results Prior to high-dose chemotherapy, 37.7% of the patients were in complete remission (CR) and 45.3% were in partial remission (PR), and 17% had stable or progressive disease. After high-dose chemotherapy and PBSC, 44 out of 51 patients achieved CR (86.2%). CR was achieved in 24 out of 33 patients (72.7%) who were transplanted in a marginally active phase of the disease. At a median followup of 25.4 months (1.8–131.3 months) after ASCT, 13 patients relapsed/progressed and 8 patients died. The estimated 2-year overall survival (OS) was 81.9%, and event-free survival (EFS) was 59.3%. Conclusion High-dose chemotherapy followed by ASCT is an effective conditioning regimen in relapsed/refractory lymphoma patients who are undergoing ASCT.PubMedWo