Browsing by Author "Buyukasik, Yahya"

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Both Granulocytic and Non-Granulocytic Blood Cells Are Affected in Patients with Severe Congenital Neutropenia and Their Non-Neutropenic Family Members: An Evaluation of Morphology, Function, and Cell Death
(2018) Olcay, Lale; Unal, Sule; Onay, Huseyin; Erdemli, Esra; Ozturk, Aysenur; Billur, Deniz; Metin, Ayse; Okur, Hamza; Yildirmak, Yildiz; Buyukasik, Yahya; İkinciogullari, Aydan; Falay, Mesude; Ozet, Gulsum; Yetgin, Sevgi; 30040071
Objective: To examine granulocytic and non-granulocytic cells in children with severe congenital neutropenia (SCN) and their non-neutropenic parents. Materials and Methods: Fifteen patients with SCN and 21 non-neutropenic parents were evaluated for a) CD95, CD95 ligand, annexin V, propidium iodide, cell cycle, and lymphocyte subsets by flow cytometry; b) rapid cell senescence (of leukocytes) by senescence-associated beta-galactosidase stain; c) aggregation tests by aggregometer; d) in vitro bleeding time by PFA-100 instrument; e) mepacrine-labeled dense granule number of thrombocytes by fluorescence microscope; and f) hematomorphology by light and electron microscope. HAX1, ELANE, G6PC3, CSF3R, and JAGN1 mutations associated with SCN were studied in patients and several parents. Results: Significant increase in apoptosis and secondary necrosis in monocytes, lymphocytes, and granulocytes of the patients and parents was detected, irrespective of the mutation type. CD95 and CD95 ligand results implied that apoptosis was non-CD95-mediated. Leukocytes of 25%, 12.5%, and 0% of patients, parents, and controls showed rapid cell senescence. The cell cycle analysis testable in four cases showed G1 arrest and apoptosis in lymphocytes of three. The patients had HAX1 (n=6), ELANE (n=2), G6PC3 (n=2), and unidentified (n=5) mutations. The CD3, CD4, and NK lymphocytes were below normal levels in 16.6%, 8.3%, and 36.4% of the patients and in 0%, 0%, and 15.4% of the parents (controls: 0%, 0%, 5.6%). The thrombocytes aggregated at low rates, dense granule number/thrombocyte ratio was low, and in vitro bleeding time was prolonged in 37.5%-66.6% of patients and 33.3%-63.2% of parents (vs. 0% in controls). Under electron and/or light microscope, the neutrophils, monocytes, lymphocytes, and thrombocytes in the peripheral blood of both patients and parents were dysplastic and the bone marrow of patients revealed increased phagocytic activity, dysmegakaryopoiesis, and necrotic and apoptotic cells. Ultrastructurally, thrombocyte adhesion, aggregation, and release were inadequate. Conclusion: In cases of SCN, patients' pluripotent hematopoietic stem cells and their non-neutropenic parents are both affected irrespective of the genetic defect.
Generic Imatinib Mesylate is as Effective as Original Glivec in the Clinical Management of CML
(2015) Malkan, Umit Y.; Aksu, Salih; Aktimur, Sude H.; Atay, Hilmi; Bektas, Ozlen; Buyukasik, Yahya; Demiroglu, Haluk; Eliacik, Eylem; Esme, Mert; Hacihanefioglu, Abdullah; Gunes, Gursel; Goker, Hakan; Karakus, Sema; Kilickap, Saadettin; Koca, Ebru; Ozcebe, Osman I.; Sayinalp, Nilgun; Tarkun, Pinar; Turgut, Mehmet; Haznedaroglu, Ibrahim C.
Unsustainable drug prices in chronic myeloid leukemia (CML) and cancer may be causing harm to patients. The aim of this multi-center study is to assess the efficacy of generic imatinib mesylate (IM) over Glivec in terms of hematological, cytogenetic, and molecular responses in CML. The data of 120 CML patients, who were treated with generic or original form of IM, were obtained from six different hematology clinics in Turkey between the years of 2009-2014 and analyzed retrospectively. Initial evaluation revealed that only one patient who was using original molecule switched to second generation tyrosine kinase inhibitor (TKI). In this period, hematological response(HR) was observed in 99.2% of the patients, cytogenetic response (CR) was observed in 88.7% of the patients (47 of 53), and molecular response (MR) was observed in 75% of the patients. Clinicians had a tendency to prefer generic molecules in each sequent visit, and this switch rate was statistically significant (p<0.001). 11 patients, who were using original molecules during all cohorts, switched to second generation TKI. On the other hand, only one patient, who was using generic molecules, switched to second generation TKI. Our paper may help to clarify the doubts about the efficacy of generic IM compared to original molecule. In our study we did not find any significant difference in HR, CR, and MR for original and generic drugs in each visit. Herein, we find low rates of need to switch to second generation TKIs with generic IM and no difference in treatment responses between generic and original molecules that confirms the non-inferiority of generic TKIs over original molecules.
Improving Survival Besides the High Early Mortality Rate in Acute Promyelocytic Leukemia
(2022) Malkan, Umit Yavuz; Koca, Ebru; Buyukasik, Yahya
The improvement in survivals of acute promyelocytic leukemia (APL) patients are still debated. In this study, we aimed to analyze the survival and early mortality (EM) rates of APL patients. In this study, de-novo APL patients who was followed up by our clinic between the years 2003-2021, were retrospectively analyzed. Patients were divided in according to their year of diagnosis, 2003-2013 (n= 33) and 2014-2021 (n= 19) groups. The 2-years survival is 52.5% and 78.9% in 2003-2013 group and 2014-2021 group, respectively, p= 0.069.The EM was not statistically different between the 2003-2013 and 2014-2021 groups (11/22 vs.4/15, p= 0.347). The 2-years survival ratio is 75.3% and 36.4% in modified-AIDA and IDA-ARA/C-ATRA treatment groups, respectively, p= 0.003. EM according to treatment groups were 7/38 versus 7/11 in modified-AIDA and IDA-ARA/C-ATRA,respectively, p= 0.001.White blood cell count >= 10000/mu l is the most important predictor of EM with overall prediction of 79.5%. The second most important factor which is related with EM is infection of patients at presentation.If these two factors are considered together there is an 84.1% overall prediction of EM. The third and last significant factors that effects EM is the induction treatment protocol. If these three significant parameters considered all together,there would be an 88.6% overall prediction of EM. The overall survival of APL patients is slightly improved between the years 2014-2021 compared to 2003-2013. The reason of this improvement is not the reduction of EM in the APL patients. Better diagnostic tools and molecular monitoring and better supportive care may have played role in the improvement of the survival of APL patients. In order to further improvement of the overall survival of APL patients, EM rates must be decreased. According to our study results, rapid and efficient treatment of infections in APL patients look like the only modifiable parameter that is related with EM.
Prognostic Factors for Survival of Elderly Patients with Acute Myeloid Leukemia after Intensive Chemotherapy Validation of 3 Popular Prognostic Models
(2014) Koca, Ebru; Halacoglu, Aysun; Malkan, Umit Yavuz; Arica, Deniz; Karakus, Sema; Goker, Hakan; Haznedaroglu, Ibrahim C.; Sayinalp, Nilgun; Buyukasik, Yahya; https://orcid.org/0000-0002-7566-4456; https://orcid.org/0000-0001-6055-6404; https://orcid.org/0000-0001-5444-4895; W-8713-2019; HZJ-4538-2023; J-2796-2019