Bahriye Payzin

Paraneoplastic Cerebellar Degeneration in Association with Hodgkin’s Disease: A Report of Two Cases

Two patients with paraneoplastic cerebellar degeneration accompanying Hodgkins disease were treated with plasma exchange in combination with chemotherapy or radiation therapy, respectively. Significant improvement in neurologic symptoms was obtained in 1 of them.

Is the BFM Regimen Feasible for the Treatment of Adult Acute Lymphoblastic Leukemia? A Retrospective Analysis of the Outcomes of BFM and Hyper-CVAD Chemotherapy in Two Centers

Multiple induction regimens have been developed for adult patients with acute lymphoblastic leukemia (ALL). However, there have been no prospective randomized trials that directly compare these regimens. In this study, we wanted to evaluate the outcome of 50 adult ALL patients treated with BFM (i.e. Berlin-Frankfurt-Munster, n = 20) and hyper-CVAD (n = 30) protocols between March 2006 and October 2012. The median age was 25 years in the BFM group and 30.5 years in the hyper-CVAD group with a male/female ratio of 15:5 and 17:13, respectively. Forty-five percent of the patients in the BFM group and 30.3% in the hyper-CVAD group were <25 years old. The majority of cases were B cell in origin (80% in the BFM group and 70% in the hyper-CVAD group). Complete remission after induction therapy was achieved in 95 and 96% of the patients, respectively. The median follow-up time was 37 months. The 5-year survival rate was higher in the BFM group than in the hyper-CVAD group (59 vs. 34%). There were also no complications which could cause a delay during the hyper-CVAD regimen. Both chemotherapies were well tolerated. None of the patients died from drug-related toxicity. Only mild liver enzyme elevations were seen as toxicity in the BFM group; these did not cause any delay in therapy. The BFM regimen seems to be feasible for adult patients with ALL in terms of tolerability and efficacy, especially in young adults.

FAS/FASL gene polymorphisms in Turkish patients with chronic myeloproliferative disorders

Introduction Chronic myeloproliferative disorders (CMPD) are chronic myeloid hematological disorders, characterized by increased myeloid cell proliferation and fibrosis. Impaired apoptotic mechanisms, increased cell proliferation, uncontrolled hematopoietic cell proliferation and myeloaccumulation may contribute to the pathogenesis of CMPD. The aim of our study was to show the possible role of FAS/FASL gene polymorphisms in CMPD pathogenesis and investigate the association with clinical parameters and susceptibility to disease. Material and methods We included 101 (34 polycythemia vera (PV), 23 primary myelofibrosis (PMF), 44 essential thrombocythemia (ET)) CMPD patients diagnosed according to the WHO classification criteria and 95 healthy controls in this study. All the patients and the controls were investigated for FAS/FASL gene expression, allele frequencies and phenotype features, and also FAS mRNA levels were analyzed. Results Chronic myeloproliferative disorders patients showed increased FAS-670AG + GG genotype distribution compared with the control group (p < 0.05). While the A allele was more frequent in both groups, AG genotype was more frequent in CMPD patients. There was no association between FAS-670A>G gene polymorphism and some clinical parameters such as splenomegaly and thrombosis (p > 0.05). No statistically significant difference in FASL+843C>T genotype or allele frequency was found between groups (p > 0.05). Moreover, no statistically significant difference was detected in FASL and JAK2V617F mutations (p > 0.05). FAS mRNA expression was 1.5-fold reduced in patients compared to healthy subjects. Conclusions According to our findings, FAS/FASL gene expression may contribute to the molecular and immunological pathogenesis of CMPD. More investigations are needed to support these data.

The Effect of FcγRIIIA Gene Polymorphism on the Treatment of Diffuse Large B-cell Non-Hodgkin Lymphoma: A Multicenter Prospective Observational Study

Objective: The curative treatment approach for diffuse large B-cell lymphoma (DLBCL) is controversial even in the rituximab (R) era. The aim of this study was to examine the FcγRIIIA gene polymorphism distribution of DLBCL patients who had been treated with R-CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy. Furthermore, we investigated the impact of FcγRIIIA gene polymorphism on the overall response rate (ORR) and overall survival (OS). Materials and Methods: Patients from 3 centers in the Aegean region of Turkey who had newly diagnosed CD20-positive DLBCL were enrolled in the study. The single nucleotide polymorphisms of the FcγRIIIA gene were analyzed by real time-PCR. The response to treatment was determined in the middle and at the end of the protocol. During 2 years of follow-up, the patients were clinically and radiologically evaluated for disease status every 3 months. Results: Thirty-six patients were included in the study and the distributions of F/F, V/F, and V/V types of alleles of FcγRIIIA were 25%, 50%, and 25%, respectively. Twenty-seven patients were considered as evaluable according to ORR and OS. The patients’ ORR was 87.5%, 100%, and 50% in the F/F, V/F, and V/V allele groups, respectively. We did not establish any statistically significant differences among the 3 alleles groups in respect to ORR (p=0.93). The OS within 2 years in the F/F, V/F, and V/V allele groups was 62.5%, 100%, and 100%, respectively. The OS in the F/F allele group was found to be lower than in the other 2 allele groups (p=0.01). Conclusion: The distribution of gene polymorphisms in our study group was similar to those of previous studies. While ORR was similar between the groups, our results highlight a lower OS in F/F patients compared to other allele groups of FcγRIIIA.

Eltrombopag for the Treatment of Immune Thrombocytopenia: The Aegean Region of Turkey Experience.

Objective: Immune thrombocytopenia (ITP) is an immune-mediated disease characterized by transient or persistent decrease of the platelet count to less than 100x109/L. Although it is included in a benign disease group, bleeding complications may be mortal. With a better understanding of the pathophysiology of the disease, thrombopoietin receptor agonists, which came into use in recent years, seem to be an effective option in the treatment of resistant cases. This study aimed to retrospectively assess the efficacy, long-term safety, and tolerability of eltrombopag in Turkish patients with chronic ITP in the Aegean region of Turkey. Materials and Methods: Retrospective data of 40 patients with refractory ITP who were treated with eltrombopag in the Aegean region were examined and evaluated. Results: The total rate of response was 87%, and the median duration of response defined as the number of the platelets being over 50x109/L was 19.5 (interquartile range: 5-60) days. In one patient, venous sinus thrombosis was observed with no other additional risk factors due to or related to thrombosis. Another patient with complete response and irregular follow-up for 12 months was lost due to sudden death as the result of probable acute myocardial infarction. Conclusion: Although the responses to eltrombopag were satisfactory, patients need to be monitored closely for overshooting platelet counts as well as thromboembolic events.

The value of serum immunoglobulin free light chain assessment in patients with monoclonal gammopathies and acute renal failure.

Objective: Immunoglobulin free light chain (FLC) abnormalities are common in patients with monoclonal gammopathies and the kidneys are the most affected organs. Immunoassays that provide quantitative measurement of FLC in serum indicate monoclonal FLC production based on the presence of an abnormal FLC kappa:lambda (κ:λ) ratio. The aim of this study was to assess the utility of serum FLC measurement as a diagnostic tool for detecting plasma cell dyscrasias in comparison to standard assays, and to ascertain its sensitivity and specificity in patients with acute renal failure (ARF). Material and Methods: Sera from 82 patients with ARF were assessed using serum protein electrophoresis (SPE), serum immunofixation electrophoresis (SIFE), and FLC measurement. The sensitivity and specificity of the FLC ratio in identifying which ARF patients had multiple myeloma (MM) was compared to those of SPE and SIFE. Results: Among the 82 patients with ARF, 7 were diagnosed as MM using SPE, SIFE, and bone marrow biopsy techniques. In total, 8 patients did not have a FLC κ:λ ratio that was within the published reference range (0:26-1:65); the FLC κ:λ ratio based on FLC measurement had a specificity of 96% and sensitivity of 71%, and positive and negative predictive values of 62.9% and 97.3%, respectively, for the diagnosis of MM. Conclusion: The sensitivity and specificity of the FLC κ:λ ratio for diagnosing MM in patients that presented with ARF were lower than those of SPE and SIFE. To further delineate the utility of the FLC κ:λ ratio additional prospective, well-designed large-scale studies are needed. Conflict of interest:None declared.

A multicenter experience of thrombotic microangiopathies in Turkey: The Turkish Hematology Research and Education Group (ThREG)-TMA01 study

Thrombotic microangiopathies (TMAs) are rare, but life-threatening disorders characterized by microangiopathic hemolytic anemia and thrombocytopenia (MAHAT) associated with multiorgan dysfunction as a result of microvascular thrombosis and tissue ischemia. The differentiation of the etiology is of utmost importance as the pathophysiological basis will dictate the choice of appropriate treatment. We retrospectively evaluated 154 (99 females and 55 males) patients who received therapeutic plasma exchange (TPE) due to a presumptive diagnosis of TMA, who had serum ADAMTS13 activity/anti-ADAMTS13 antibody analysis at the time of hospital admission. The median age of the study cohort was 36 (14-84). 67 (43.5%), 32 (20.8%), 27 (17.5%) and 28 (18.2%) patients were diagnosed as thrombotic thrombocytopenic purpura (TTP), infection/complement-associated hemolytic uremic syndrome (IA/CA-HUS), secondary TMA and TMA-not otherwise specified (TMA-NOS), respectively. Patients received a median of 18 (1-75) plasma volume exchanges for 14 (153) days. 81 (52.6%) patients received concomitant steroid therapy with TPE. Treatment responses could be evaluated in 137 patients. 90 patients (65.7%) achieved clinical remission following TPE, while 47 (34.3%) patients had non-responsive disease. 25 (18.2%) non-responsive patients died during follow-up. Our study present real-life data on the distribution and follow-up of patients with TMAs who were referred to therapeutic apheresis centers for the application of TPE.

Rapidly Growing Thyroid Mass: An Unusual Case of Acute Lymphoblastic Leukemia.

In conclusion CFH gene analysis was performed to confirm whether the patient had aHUS or not. However, we have found CFH gene mutations that are not specific for aHUS. Epigenetic factors might have triggered the patient’s phenotype. Also p.His402Tyr mutation may cause TMA with a milder clinic feature than that of other aHUS specific CFH gene mutations. Conflict of Interest Statement The authors of this paper have no conflicts of interest, including specific financial interests, relationships, and/ or affliations relevant to the subject matter or materials included.