The effect of serum lipid levels on peripheral blood hematopoietic stem cell levels.

INTRODUCTION: There are limited numbers of available retrospective studies on various hematological diseases treated with stem cell mobilization therapy. In the present study, we aimed to demonstrate the effects of serum lipid levels on peripheral blood CD34+ (PBCD34+) cell counts as well as the changes in serum lipid levels during stem cell mobilization process. METHOD: PBCD34+ cell counts were compared between hypercholesterolemic patients and healthy individuals. Additionally, total cholesterol (TChol), LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C), and triglyceride (TG) levels were measured from healthy donors who underwent stem cell mobilization, at different time points (prior to filgrastim [phase 1], prior to apheresis [phase II], and the first week following apheresis [phase III]. RESULTS: In the hypercholesterolemia group, the PBCD34+ cell count was found to be higher among patients with elevated LDL-C (2.6 ± 0.35/µL vs. 1.7 ± 0.17/µL, p = 0.003) and TChol (2.6 ± 0.34/µL vs. 1.7 ± 0.14/µL, p = 0.006) in comparison to the healthy controls. In the mobilization group, phase II HDL-C levels (35.3 ± 2.8 mg/dL) were found to be lower than both phase I (45.6 ± 2.1 mg/dL) and phase III (44.5 ± 2.6 mg/dL) (p = 0.007). Phase II TChol levels (183.5 ± 10.0 mg/dL) were lower than both phase I (216.8 ± 8.5 mg/dL) and phase III (212.2 ± 8.4 mg/dL) (p = 0.02). At phase II, there was an inverse correlation between PBCD34+ cell count and HDL-C (r = - 0.57, p = 0.003). DISCUSSION: Our results indicate that, while increased LDL-C level is the determinant of baseline PBCD34+ cell count, reduced HDL-C is the determinant of PBCD34+ cell count during mobilization process.

Efficacy and safety of ruxolitinib in patients with myelofibrosis: a retrospective and multicenter experience in Turkey

Background/aim: The aim of this study is to assess the efficacy and safety of ruxolitinib in patients with myelofibrosis. Materials and methods: From 15 centers, 176 patients (53.4% male, 46.6% female) were retrospectively evaluated. Results: The median age at ruxolitinib initiation was 62 (28­87) and 100 (56.8%) of all were diagnosed as PMF. Constitutional symptoms were observed in 84.7%. The median initiation dose of ruxolitinib was 30 mg (10­40). Dose change was made in 69 (39.2%) patients. Forty seven (35.6%) and 20 (15.2%) of 132 patients had hematological and nonhematological adverse events, respectively. The mean spleen sizes before and after ruxolitinib treatment were 219.67 ± 46.79 mm versus 199.49 ± 40.95 mm, respectively (p < 0.001). There was no correlation between baseline features and subsequent spleen response. Overall survival at 1-year was 89.5% and the median follow up was 10 (1­55) months. We could not show any relationship between survival and reduction in spleen size (p = 0.73). Conclusion: We found ruxolitinib to be safe, well tolerated, and effective in real-life clinical practice in Turkey. Ruxolitinib dose titration can provide better responses in terms of not only clinical benefit but also for long term of ruxolitinib treatment.

Investigating the cytotoxic and apoptotic effects of sunitinib upon K-562 chronic myelogenous leukemia cell line and assessment of gene profiling.

OBJECTIVE: Tyrosine kinase inhibitors (TKIs) which efficiently inhibit BCR-ABL are highly effective for clinical treatment of chronic myeloid leukemia (CML), but development of resistance to TKIs is a big challenge to treatment. Sunitinib is a multitargeted TKI targeting vascular endothelial growth factor receptor and is defined a safe and effective candidate target, but its effect on other signaling pathways is unknown. To investigate the cytotoxic and apoptotic effect of sunitinib in CML cell model K-562 on JAK-STAT signaling pathway components, suppressor genes and oncogenes, hematopoiesis-related genes, cell cycle and VEGF pathway components, and mRNA level expression changes was aimed. MATERIALS AND METHODS: Sunitinib's effective dose cytotoxic IC50 was determined by trypan blue and WST-1 cell proliferation assay tests. Expression levels of target genes were determined by quantitative reverse transcriptase polymerase chain reaction simultaneously after sunitinib application. Protein expression analysis was determined by "WesternBreeze Chromogenic Kit-Anti-Rabbit" based on the principles of the application kit by Western blot analysis. RESULTS: Assessing the cytotoxicity of K-562 cells following sunitinib treatment revealed that sunitinib decreased cell proliferation in a time- and dose-dependent manner. According to the sunitinib inhibition curve, IC50 dose was calculated as 3.5 µM at 48th h for K-562 cells and apoptosis assays pointed that sunitinib induces apoptotic cell death of leukemic cells at moderate levels. CONCLUSION: Our study supports that sunitinib might be used as a novel therapeutic target to trigger apoptosis in CML cells which in turn might accelerate therapeutic response in regard to inhibiting oncogenes and enhancing tumor suppressors in cooperation with cell cycle regulatory genes.

Hemophagocytic Lymphohistiocytosis in Adults: Low Incidence of Primary Neoplasm as a Trigger in a Case Series from Turkey.

Hemophagocytic Lymphohistiocytosis (HLH) is an indicator of an exaggerated immune response and eventually adverse outcomes. This study aimed to investigate the clinical and laboratory features and outcomes of patients with HLH. The medical records of 26 HLH adult patients (≥ 16 years of age) were retrospectively analyzed. Gender, age, the duration of fever, time to diagnosis, etiology and laboratory data were extracted from the records. The mean age was 38 ± 18 years, and 15 (58%) patients were female. A total of nine cases had infectious diseases; four cases had rheumatologic diseases, three cases had hematological malignancies while nine cases could not have a definitive diagnosis. The median time to detection of HLH was 20 days (IQR: 8-30 d). Of the 25 patients, 11 (44%) died. The erythrocyte sedimentation rates of the surviving and non-surviving patients were 39 ± 22 mm/h and 15 ± 13 mm/h, respectively. When a long-lasting fever is complicated by bicytopenia or pancytopenia (especially), clinicians should promptly consider the possibility of HLH syndrome to improve patients' prognosis.

Carfilzomib experience in relapsed/refractory multiple myeloma: 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.

Evaluation of bone mineral density and related parameters in patients with haemophilia: a single center cross-sectional study.

Haemophilia has been associated with low bone mineral density (BMD) probably due to some predisposing factors. The aim of this study was to evaluate the relationship between BMD and potential clinical predictors in adult haemophilic patients. Fortynine patients with moderate and severe haemophilia were enrolled. BMD was measured by Dual Energy X-Ray Absorptiometry (DXA) and blood tests were performed for vitamin D, calcium, phosphore, alkaline phosphatase and parathormone levels. Functional Independence Score in Haemophilia (FISH) and Haemophilia Joint Health Score (HJHS) were used to assess musculoskeletal functions. Body mass index (BMI), Hepatitis C virus (HCV)/Human immunodeficiency virus (HIV) seropositivity and smoking status were also recorded. BMD was found lower than expected for reference age in 34.8% of patients of less than 50 years old. In patients older than 50 years, 66.6% of them had osteoporosis and 33.3% of them had normal BMD. FISH score was statistically significant correlated with BMD of total hip (TH) and femur neck (FN) but not with lumbar spine (LS). In eligible patients, there was also a statistically significant correlation between BMD of TH and HJHS. Vitamine D deficiency was common and found in 77.5% of patients, although there was no significant correlation with BMD. Also no correlation was found between BMD and blood tests, HCV/HIV status, BMI and smoking. This study confirmed that patients with haemophilia have an increased prevelance of low BMD even in younger group. Our results showed that there are significant correlations between FISH score and BMD of TH and FN and also between HJHS score and BMD of TH. Thus, using scoring systems may be beneficial as a simple predictors of BMD to reflect the severity of haemophilic arthropathy.

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.

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.

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.

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.

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.

Multidisciplinary clinical management of paroxysmal nocturnal hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired disease caused by clonal expansion of one or more hematopoietic stem cell (HSC) lines due to a somatic mutation of the phosphatidylinositol glycan anchor (PIG-A) gene located on Xp22.1. PNH incidence is 1.5-2 cases per million of the population per year. PNH can affect multiple systems in the body and requires multidisciplinary clinical management. Patients can manifest with severe pancytopenia, life-threatening thrombosis affecting the hepatic, abdominal, cerebral, and subdermal veins, and high requirements for blood transfusion due to haemolytic anemia. PNH can also be associated with bone marrow failure. Advances in diagnostic techniques and a targeted therapeutic approach for PNH have emerged in the last two decades. Eculizumab, a promising humanized monoclonal antibody against C5, is the first approved therapy for PNH.

PNH is a debilitating, fatal but treatable disease: same disease, different clinical presentations.

Paroxysmal nocturnal hemoglobinuria (PNH) is a disease characterized by chronic persistent hemolysis, multi-organ damage and eventually multiple organ failure. PNH develops as a result of increased sensitivity to complement due to an acquired deficiency of certain glycosylphosphatidylinositol (GPI)-linked proteins. The clinical presentation of PNH varies greatly from one patient to another. We present three cases of PNH with different clinical presentations to illustrate the debilitating nature of the disease, possible fatal outcomes, and the need to timely diagnosis and targeted therapy. These cases also underline the need for increased awareness of PNH among relevant healthcare specialties. PNH should be considered as a differential diagnosis in patients with unexplained abdominal pain, dyspnea, renal failure, thrombosis and non-immune hemolytic anemia.

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.

Immune thrombocytopenic purpura: new biological therapy of an old disease.

Immune Thrombocytopenic Purpura (ITP) is the most common autoimmune disorder that is caused by antibody- mediated destruction of thrombocytes and impaired megakaryocyte platelet production. ITP remains a diagnosis of exclusion. Recent pathophysiologic mechanisms and therapeutical approaches of ITP have emerged. Although steroids and intravenous immunglobulins (IVIg) have still been the main therapeutic strategies, a group of patients develop resistance to those eventually and there have been some biological treatment options such as rituximab especially in the last decade. In this review article, we have summarized the therapeutic options for patients with ITP and mainly focused on the timing and potential effects of biological agents.

Evaluation of immunomodulatory drugs in multiple myeloma: single center experience.

OBJECTIVE: Multiple myeloma (MM) comprises 1% of all cancers and 10% of hematologic malignancies and known as an incurable disease. The introduction of immunomodulatory drugs (IMiDs) has brought a major shift in therapeutic paradigm in the treatment of newly diagnosed and relapsed/refractory MM patients. The aim of this study was to evaluate the relationship between response status and hematological parameters in patients with MM treated with thalidomide or lenalidomide. METHODS: Sixty-eight patients who were treated with IMiDs in Ege University, School of Medicine, Department of Hematology, between 2005 and 2012, were evaluated, retrospectively. RESULTS AND CONCLUSION: We could not find any difference between the hematological parameters before and after the treatment neither with thalidomide nor lenalidomide. However, the heterogenity of our groups, the difference in treatment strategies and potential side effects would have an impact on this result. It is needed to perform prospective clinical trials to prove that whether correction of hematological parameters would reflect the response status in patients with myeloma that treated with IMiDs.