Melda Cömert Özkan

Peripheral blood stem cell mobilization from healthy donors

Most frequently used graft of hematopoietic stem cells (HSCs) for allogeneic transplantation is peripheral blood stem cells (PBSCs) that are collected after mobilization with frequently granulocyte colony-stimulating factor (G-CSF). Administration of the optimal dose of G-CSF while preserving the donor health is one of the most important points for sufficient PBSC mobilization and harvest. We hereby tried to summarize characteristic features, potential side effects and main topics in peripheral blood stem cell mobilization from healthy donors.

Progressive Transformation of Germinal Centers: Single-Center Experience of 33 Turkish Patients

Progressive transformation of germinal centers (PTGCs) is a benign disease of the lymph nodes that is rarely associated with Hodgkin disease. We reviewed the clinical and pathologic features of PTGCs and the relationship of PTGCs with lymphoid neoplasia in an adult population. The data from 33 patients who were diagnosed with PTCGs were retrospectively analyzed. Of the 33 PTGC patients, 48.5% were men and 51.5% were women, with a mean age of 43.8 years at diagnosis. Most of the enlarged and excised lymph nodes were cervical and axillary. Diffuse large B-cell lymphoma and nodular lymphocyte predominant Hodgkin lymphoma was detected concurrent with PTGC in 2 patients. Also, PTGCs was detected 3 years after the diagnosis of diffuse large B-cell lymphoma, nodular lymphocyte predominant Hodgkin lymphoma, and T-cell-rich B-cell lymphoma in 3 patients. No relapse was found in the patients with lymphoma, and no progression to lymphoma was detected during the follow-up of the other patients. PTGCs is not considered a premalignant entity; however, the development of lymphoma has been reported rarely. If PTGCs occurs in the follow-up process of patients with lymphoma, the follow-up intervals should be shortened.

Investigating the Role of JAK/STAT Pathway on Dasatinib-Induced Apoptosis for CML Cell Model K562

We aimed to evaluate the cytotoxic and apoptotic effects of dasatinib (BMS-354825) on K562 chronic myeloid leukemia (CML) cells and to examine the roles of STAT genes on dasatinib-induced apoptosis. The results showed that dasatinib decreased proliferation and induced apoptosis in K562 cells in a dose- and time-dependent manner. mRNA and protein levels of STAT5A and STAT5B genes were significantly reduced in dasatinib-treated K562 cells. These data indicated that STAT inhibition by dasatinib might be therapeutic in JAK/STAT pathway-associated malignancies after confirmation with clinical studies.

Ocular Adnexal Lymphomas: Single-Center Experience

Ocular adnexal lymphoma (OAL) is a rare manifestation of non-Hodgkin lymphoma consisting of the tissues and structures surrounding the eye that include the conjunctiva, eyelids, lacrimal gland, and orbital soft tissues. OAL comprise 1% to 2% of all non-Hodgkin lymphomas and about 8% of the extranodal lymphomas; however, the incidence of OAL has increased by approximately 6% annually in last 2 decades, and OAL now represents the majority of orbital malignancies. There are no uniform treatment guidelines for OAL. Because of high local and extraorbital recurrence rates, appropriate local, systemic, or combined treatment must be applied.

Carfilzomib experience in relapsed/refractory multiplemyeloma: a single-center experience

Background/aim: Carfilzomib (CFZ) is a new-generation proteasome inhibitor with significant activity in relapsed or refractory multiple myeloma (R/R-MM). We have retrospectively evaluated R/R-MM patients who were treated with CFZ plus dexamethasone. Materials and methods: Twenty-one R/R-MM patients who were treated with CFZ plus dexamethasone between October 2013 and January 2016 were screened. The patients were followed until March 2016 after CFZ treatment. Results: Ten (47.6%) of the patients were female and 11 (52.4%) of them were male. The median age was 62 (47-76) years. The median number of prior treatment lines was 3 (2-7). The median number of administered cycles of treatment for CFZ was 4 (1-10). The median overall response rate was 26.3%. The most common hematological adverse events were anemia and thrombocytopenia (38%). The most common nonhematological adverse event was fatigue (71.4%). One patient died because of a cerebrovascular event and 1 patient died because of pneumonia during the treatment period. The median duration of response rate and time to next therapy were 8 (7-9) and 3 (2-16) months, respectively. The median overall survival was 8 (0.5-33) months. Conclusion: Despite the small number of patients, our results suggest that CFZ provides acceptable responses in heavily pretreated R/R-MM patients.

TET2, ASXL1, IDH1, and IDH2 Single Nucleotide Polymorphisms in Turkish Patients with Chronic Myeloproliferative Neoplasms

We aimed to determine the genotype distribution, allele frequency, and prognostic impact of IDH1/2, TET2, and ASXL1 single nucleotide polymorphisms (SNPs) in myeloproliferative neoplasms (MPNs). TET2 (rs763480), ASXL1 (rs2208131), and IDH1 (rs11554137) variant homozygous genotype frequencies were found at rates of 1.5%, 9.2%, and 2.3%, respectively. No IDH2 SNP was identified. IDH1 and TET2 frequencies were 5% in essential thrombocythemia (ET) and 1.7% in ET and 5% in primary myelofibrosis (PMF), respectively. ASXL1 frequencies were 8.3%-10% in MPN subgroups. The TET2 mutant allele T and ASXL1 mutant allele G had the highest frequencies with 0.272 in the PMF and 0.322 in the polycythemia vera (PV) group, respectively. There was no impact of the SNPs on prognosis. IDH1 frequency in MPNs was found similar to the literature. ASXL1 frequencies were similar between ET, PV, and PMF patients. The ASXL1 and TET2 allele frequencies of the Turkish population are similar to those of the European population. The role of SNPs in MPNs might be further evaluated in larger multicenter studies.

Determining expression of miRNAs that potentially regulateSTAT5A and 5B in dasatinib-sensitive K562 cells

In the era of tyrosine kinase inhibitors, resistance still constitutes a problem in chronic myeloid leukemia (CML) patients; thus, new pathway-specific inhibitors like miRNAs have become important in the treatment of refractory patients. There are no satisfying data regarding the miRNAs and anti-miRNA treatment targeting STAT5A and 5B. In this study, we first researched the effect of dasatinib on apoptosis in the CML cell line K562. The expressions of miRNAs possibly targeting both STAT5A and 5B were then determined. The down- and upregulation of the miRNAs were compared using the ΔΔCT method. At the last stage of the study, we used a new primer probe in order to validate the results. The level of hsa-miR-940 was decreased 4.4 times and the levels of hsa-miR-527 and hsa-miR-518a-5p were increased 12.1 and 8 times, respectively, in the dasatinib-treated group when compared to the control group. We detected similar results in the validation step. As a conclusion, we determined the expression profiles of miRNAs targeting STAT5A and 5B that had an important role in the pathogenesis of CML. The data obtained could lead to determining new therapeutic targets for CML patients.

Primary Cutaneous Lymphomas and Interferon Treatment

Primary cutaneous lymphomas (PCLs) are the second most common group of extranodal non-Hodgkin lymphomas (NHL) with an estimated annual incidence of 1/100.000. Interferons (IFNs) are used in mono or combination therapy for cutaneous lymphomas especially for cutaneous T-cell lymphomas (CTCL) for years. IFN-α is the most widely-used type for cutaneous lymphomas. IFN-α has been shown to be a highly active agent in CTCL with response rates ranging from 40% to 80%. In this review, the current information about PCLs and IFNs treatment is summarized. Review Article

Toxic epidermal necrolysis associated with radiotherapy and phenytoin in a patient with non-Hodking's lymphoma: A case report.

Toxic epidermal necrolysis (TEN) is a disease which is characterized by fever and desquamation of the skin and mucosal membranes. It is usually related with drugs, especially aromatic anticonvulsants which are recognized as the most common cause of this disorder. Cranial irradiation may act as a precipitating factor along with anticonvulsants for the development of TEN. We report a 28-year-old patient with central nervous system (CNS) relapsed non-Hodgkin lymphoma (NHL) who developed TEN after cranial radiotherapy and concurrent phenytoin treatment.