Mesut Ayer

First line treatment of chronic phase chronic myeloid leukaemia patients with the generic formulations of imatinib mesylate

in the prevalence of growth, endocrine and vitamin D abnormalities among the various thalassaemia syndromes in North America. British Journal of Haematology, 146, 546–556. Vogiatzi, M.G., Macklin, E.A., Fung, E.B., Cheung, A.M., Vichinsky, E., Olivieri, N., Kirby, M., Kwiatkowski, J.L., Cunningham, M., Holm, I.A., Lane, J., Schneider, R., Fleisher, M., Grady, R.W., Peterson, C.C., Giardina, P.J. & Thalassemia Clinical Research Network (2009b) Bone disease in thalassemia: a frequent and still unresolved problem. Journal of Bone and Mineral Research, 24, 543–557.

Outcomes of Chronic Myeloid Leukemia Patients With Early Molecular Response at 3 and 6 Months: A Comparative Analysis of Generic Imatinib and Glivec

Micro‐Abstract We retrospectively evaluated 90 patients with chronic myeloid leukemia receiving either upfront original imatinib (OI) or generic imatinib (GI) for the effect of the early molecular response on the long‐term outcome. We demonstrated that achieving an optimal response at 3 and 6 months in patients receiving either first‐line GI or OI was clearly associated with greater response and event‐free survival rates. Background: The molecular response at 3 months of the original imatinib (OI) in patients with chronic myeloid leukemia has prognostic significance; however, this has never been tested for generic imatinib (GI). Patients and Methods: We evaluated the BCR‐ABL1 [international reporting scale (IS)] transcript levels at 3 and 6 months to determine whether an early molecular response (EMR) had a prognostic effect on the outcome among chronic myeloid leukemia patients receiving GI. Ninety patients were divided into 2 groups, according to the imatinib they received, as OI (group A) and GI (group B). Results: Two groups were equally balanced for age, gender, Sokal risk score, and optimal response. The 2 groups did not differ in achieving an EMR at 3 months, and patients with EMR at 3 months had significantly superior complete cytogenetic response and major molecular response rates compared with patients who did not achieve an EMR in both groups. The percentage of an optimal response [BCR‐ABL1 (IS), < 1%] and a warning response [BCR‐ABL1 (IS), 1%‐10%] at 6 months was 93% and 95% for groups A and B, respectively (P = .553). Patients with an optimal response (OR) at both 3 and 6 months had significantly superior event‐free survival rates compared with patients without an OR in groups A and B. Conclusion: The results of the present study have demonstrated most probably for the first time that an OR at 3 and 6 months in patients receiving either first‐line GI and OI is clearly associated with greater response and event‐free survival rates. Prospective randomized trials with larger numbers of patients and longer follow‐up periods are needed to address the effect of EMR in patients receiving GI.

Patients treated with therapeutic plasma exchange: A single center experience

INTRODUCTION Therapeutic Plasma Exchange (TPE) is a therapeutic procedure that is used to remove high molecular weight substances from plasma. We analyzed data of patients who received TPE during the last 7 years, and focused on the efficiency of TPE in various disease groups. MATERIAL AND METHODS We studied 110 patients treated with TPE by membrane plasma separation technique from 2007 to 2013. We examined the demographic data, underlying disease, biochemical parameters, volume and type of replacement fluid, complications, concomitant treatment, the need for hemodialysis and number of TPE sessions. RESULTS One hundred ten patients, 58 male, 52 female were included. The mean age was 47.3 ± 17.6 years. A total of 734 TPE sessions were performed and the mean number of TPE sessions per patient was 6.6 ± 4.3. The underlying disease was renal transplantation in 26 patients, ANCA-associated vasculitis in 18, rapidly progressive glomerulonephritis in 17, hemolytic uremic syndrome in 11, thrombotic thrombocytopenic purpura in 9, autoimmunic hemolytic anemia in 6, focal segmental glomerulosclerosis in 6 and other diseases. Partial and complete remission was obtained in 65 (59.1%) and 24 patients (21.8%) respectively, while 14 (12.7%) patients had no response and 7 (6.4%) patients died. Complications were muscle cramps (6.4%), allergic reactions (4.5%), severe hypotension (3.6%), fever (1.8%), unconsciousness (0.9%), leukopenia (0.9%) and catheter related hematoma (0.9%). CONCLUSION According to our 7 years of experience in TPE, we can say that therapeutic plasma exchange by membrane separation technique is a useful, easy, available and effective life-saving therapeutic treatment.

An effective treatment of atypical hemolytic uremic syndrome with plasma exchange and eculizumab: A case report

Atypical hemolytic uremic syndrome is a rare thrombotic microangiopathy caused by chronic defective regulation of the complement activation. This activation results in systemic endothelial damage leading to renal failure. Eculizumab, an anti-C5 antibody, is effective in limiting complement activation in patients with aHUS and has recently came out as a therapeutic option for aHUS. Here we present a case showing that first-line eculizumab treatment successfully prevents the induction of the terminal complement cascade and blocked the progression of thrombotic microangiopathy in aHUS.

Investigation of Gene Expressions of Myeloma Cells in the Bone Marrow of Multiple Myeloma Patients by Transcriptome Analysis

Background: Multiple myeloma is a plasma cell dyscrasia characterized by transformation of B cells into malignant cells. Although there are data regarding the molecular pathology of multiple myeloma, the molecular mechanisms of the disease have not been fully elucidated. Aims: To investigate the gene expression profiles in bone marrow myeloma cells via RNA-sequencing technology. Study Design: Cell study. Methods: Myeloma cells from four patients with untreated multiple myeloma and B cells from the bone marrow of four healthy donors were sorted using a FACSAria II flow cytometer. The patient pool of myeloma cells and the control pool of B cells were the two comparative groups. A transcriptome analysis was performed and the results were analyzed using bioinformatics tools. Results: In total, 18.806 transcripts (94.4%) were detected in the pooled multiple myeloma patient cells. A total of 992 regions were detected as new exon candidates or alternative splicing regions. In addition, 490 mutations (deletions or insertions), 1.397 single nucleotide variations, 415 fusion transcripts, 132 frameshift mutations, and 983 fusions, which were reported before in the National Center for Biotechnology Information, were detected with unknown functions in patients. A total of 35.268 transcripts were obtained (71%) (25.355 transcripts were defined previously) in the control pool. In this preliminary study, the first 50 genes were analyzed with the MSigDB, Enrichr, and Panther gene set enrichment analysis programs. The molecular functions, cellular components, pathways, and biological processes of the genes were obtained and statistical values were determined using bioinformatics tools and are presented as a supplemental file. Conclusion: EEF1G, ITM2C, FTL, CLPTM1L, and CYBA are identified as possible candidate genes associated with myelomagenesis.

Purtscher-Like Retinopathy Associated with Atypical Hemolytic Uremic Syndrome

A 25-year-old woman presented with acute bilateral blurred vision and history of headache, dizziness, and syncope for three days. Her visual acuity was 20/60 in both eyes. Fundoscopy revealed multiple bilateral peripapillary yellow-white patches like cotton wool spots, intraretinal hemorrhages and macular edema. The patient was diagnosed with Purtscher-like retinopathy based on the retinal findings and lack of trauma history. She was urgently admitted to the nephrology clinic due to thrombotic microangiopathy findings (hemoglobinemia, thrombocytopenia, and acute renal failure). After excluding thrombotic microangiopathy, the patient was diagnosed with atypical hemolytic uremic syndrome (aHUS) with the clinical and laboratory findings. Eculizumab treatment was added to hemodialysis and plasmapheresis therapy. Three months after starting treatment, retinal lesions regressed and visual acuity increased to 20/20 in both eyes. To the best of our knowledge, this is the first reported case of Purtscher-like retinopathy associated with aHUS.

Evaluation of Insulin-like Growth Factor-1 and Insulin-like Growth Factor Binding Protein-3 Expression Levels in Patients with Chronic Lymphocytic Leukemia.

Objective: Chronic lymphocytic leukemia (CLL) is a disease of nonproliferating and mature-appearing B lymphocytes. Insulin-like growth factor-1 (IGF-1) is a small peptide hormone and has mitogenic and antiapoptotic effects, and insulin-like growth factor binding protein-3 (IGFBP-3) has antiproliferative effects on cells. In this study, we investigated plasma levels of both IGF-1 and IGFBP-3 in patients with CLL compared with controls, and we compared these plasma levels according to prognostic factors. Materials and Methods: Patients with newly diagnosed CLL who were being followed at the Haseki Training and Research Hospital, İstanbul, Turkey, and volunteers were included in this study. Patients were stratified according to the Rai staging system. Statistical analysis was conducted using SPSS 17.0 for Windows. Results: Forty-three patients [16 women (37%) and 27 men (63%)] were enrolled in this study. Twenty-one volunteers (11 women, 10 men) were included in the control group. The median age of the patients was 65±9 years (range: 18-63 years), and subjects in the control group were 68±8 years old (range: 18-63 years). Even though the plasma levels of IGF-1 were higher and those of IGFBP-3 were lower and the ratio of IGF-I/IGFBP-3 was higher in comparison with the control group, these differences were not statistically significant (p>0.05). In the study group, IGF-1 levels appeared to be increased in parallel to more advanced Rai stages. There were no significant differences between the other groups (p=0.105). Conclusion: Plasma IGF-I levels were found higher in patients than in the control group and plasma IGFBP-3 levels were lower; however, neither result was statistically significant. Plasma IGF level increment was observed in concordance with Rai staging. These results prompted us to think that plasma IGF-1 levels in CLL patients are correlated with tumor burden and Rai staging and therefore could be a valuable prognostic factor. Further comprehensive studies are required to support our results.

Can Positron Emission Tomography and Computed Tomography Be a Substitute for Bone Marrow Biopsy in Detection of Bone Marrow Involvement in Patients with Hodgkin's or Non-Hodgkin's Lymphoma?

Objective: Positron emission tomography and computed tomography (PET/CT) has become an important part of staging and treatment evaluation algorithms of lymphoma. We aimed to compare the results of PET/CT with bone marrow biopsy (BMB) with respect to bone marrow involvement (BMI) in patients with Hodgkin’s lymphoma (HL) and aggressive non-Hodgkin’s lymphoma (aNHL). Materials and Methods: The medical files of a total of 297 patients diagnosed with HL or aNHL and followed at the hematology clinics of 3 major hospitals in İstanbul between 2008 and 2012 were screened retrospectively and 161 patients with classical HL and aNHL were included in the study. The patients were referred for PET/CT and BMB at the initial staging. BMB was performed as the reference standard for the evaluation of BMI. Results: There were 61 (38%) HL and 100 (62%) aNHL patients. Concordant results were revealed between PET/CT and BMB in 126 patients (78%) (52 HL, 74 aNHL), 20 with positive PET/CT and BMB results and 106 with negative PET/CT and BMB results. There were discordant results in 35 patients (9 HL, 26 aNHL), 16 of them with positive BMB and negative PET/CT results and 19 of them with negative BMB and positive PET/CT results. Conclusion: We observed that PET/CT is effective to detect BMI, despite it alone not being sufficient to evaluate BMI in HL and aNHL. Bone marrow trephine biopsy and PET/CT should be considered as mutually complementary methods for detection of BMI in patients with lymphoma. In suspected focal involvement, combining biopsy and PET/CT might improve staging results.