International Forum: The Turkish perspective on apheresis activity: The Turkish apheresis registry report.

Therapeutic apheresis is an extracorporeal treatment that selectively removes abnormal cells or harmful substances in the blood that are associated with or cause certain diseases. During the last decades the application of therapeutic apheresis has expanded to a broad spectrum of hematological and non-hematological diseases due to various studies on the clinical efficacy of this procedure. In this context there are more than 30 centers performing therapeutic apheresis and registered in the apheresis database in Turkey. Herein, we, The Turkish Apheresis Registry, aimed to analyze some key articles published so far from Turkey regarding the use of apheresis for various indications.

Use of gemtuzumab ozogamicin in relapsed refractory acute myeloid leukemia: Multi-center real life data from Turkey.

We retrospectively evaluated the use of gemtuzumab ozogamicin (GO) in relapsed refractory (R/R) acute myeloid leukemia (AML) patients. Twenty-one CD33 positive R/R AML patients who received GO as a single agent in 4 hematology centers were included in this study. The median age was 59, and the median ECOG performance score was 2. According to cytogenetic analysis, 1 patient had favorable risk, 12 patients with intermediate, and 8 patients with adverse risk. The overall response rate was 52.3%. Partial response was achieved in 3 of 8 patients with adverse risk. 33.3% of patients developed grade 3 anemia. Grade 4 neutropenia and thrombocytopenia were observed in 80% of the patients. One of the patients died due to sinusoidal obstruction syndrome / veno-occlusive disease (SOS / VOD) due to GO side effects. GO may be considered as a good option for salvage therapy in R/R AML patients.

Clinical characteristics and therapeutic outcomes of paroxysmal nocturnal hemoglobinuria patients in Turkey: a multicenter experience.

The aim of this study is to collect paroxysmal nocturnal hemoglobinuria (PNH) patient data from hematology centers all over Turkey in order to identify clinical features and management of PNH patients. Patients with PNH were evaluated by a retrospective review of medical records from 19 different institutions around Turkey. Patient demographics, medical history, laboratory findings, and PNH-specific information, including symptoms at the diagnosis, complications, erythrocyte, and granulocyte clone size, treatment, and causes of death were recorded. Sixty patients (28 males, 32 females) were identified. The median age was 33 (range; 17-77) years. Forty-six patients were diagnosed as classic PNH and 14 as secondary PNH. Fatigue and abdominal pain were the most frequent presenting symptoms. After eculizumab became available in Turkey, most of the patients (n = 31/46, 67.4%) were switched to eculizumab. Three patients with classic PNH underwent stem cell transplantation. The median survival time was 42 (range; 7-183 months) months. This study is the first and most comprehensive review of PNH cases in Turkey. It provided us useful information to find out the differences between our patients and literature, which may help us understand the disease.

Evaluation of bleeding symptoms and laboratory parameters related to bleeding in sisters of patients with hemophilia A and B.

INTRODUCTION: Our purpose was to determine the bleeding risk of obligate and potential carriers, highlight the prophylactic applications before interventions for families and physicians. METHOD: Forty-six sisters who had at least one family member with hemophilia A or B were included. Laboratory parameters were tested.Bleeding tendency interrogated by a detailed questionnaire.The results were compared with 43 healthy female controls. RESULTS: Mean factor activity levels were significantly lower in sisters than control subjects (p = 0,004). Bleeding score was higher in sisters than controls (p = 0.001). Prolonged bleeding after minor injury was significantly higher in the sisters than control subjects (p = 0.008). Requiring further treatment due to prolonged bleeding after tooth extraction was significantly higher in sisters (p = 0.001). Sisters had postpartum hemorrhage lasting longer than 6 weeks than controls (p = 0.025). Menstrual period lasted longer in the sisters than controls (p < 0.001). Spontaneous epistaxis, oral and gingival bleeding were more frequently observed in sisters whose factor activity levels were 60 % or below (p = 0.014 and p = 0.047, respectively). There was no statistically significant difference between the severity of hemophilia in the affected family member and the factor levels in the sisters (p = 0.398).Spontaneous epistaxis has found to be significantly associated with the hemophilia severity in the family (p = 0.004). CONCLUSION: Clotting factor levels were found to be lower in the sisters and associated with spontaneous epistaxis, oral and gingival bleeding.Also, regardless of clotting factor levels, sisters significantly experienced more bleeding problems.Our study demonstrated the importance of taking precautions for prolonged bleeding in cases where medical interventions are inevitable in these patients.

Patterns of Hydroxyurea Prescription and Use in Routine Clinical Management of Polycythemia Vera: A Multicenter Chart Review Study

Objective: This study aimed to evaluate real-life data on patterns of hydroxyurea prescription/use in polycythemia vera (PV). Materials and Methods: This retrospective chart review study included PV patients who had received hydroxyurea therapy for at least 2 months after PV diagnosis. Data were collected from 10 representative academic medical centers. Results: Of 657 patients, 50.9% were in the high-risk group (age ≥60 years and/or history of thromboembolic event). The median duration of hydroxyurea therapy was 43.40 months for all patients; 70.2% of the patients had ongoing hydroxyurea therapy at last follow-up. Hydroxyurea was discontinued in 22.4% of the patients; the most common reason was death (38.5%). The predicted time until hydroxyurea discontinuation was 187.8 months (standard error: ±21.7) for all patients. This duration was shorter in females (140.3±37.7 vs. 187.8±29.7) (p=0.08). This trend was also observed in surviving patients aged ≥50 years at hydroxyurea initiation (122.2±12.4 vs. 187.8±30.7, p=0.03). Among the patients who were still on hydroxyurea therapy, 40.3% had a hematocrit concentration of ≥45% at their last follow-up visit, and the rate of patients with at least one elevated blood cell count was 67.8%. Conclusion: Hydroxyurea prescription patterns and treatment aims are frequently not in accordance with the guideline recommendations. Its discontinuation rate is higher in females.

A Multi-Center Study on the Efficacy of Eltrombopag in Management of Refractory Chronic Immune Thrombocytopenia: A Real-Life Experience

Objective: The aim of the present study was to evaluate the efficacy and safety of eltrombopag, an oral thrombopoietin receptor agonist, in patients with chronic immune thrombocytopenia (ITP). Materials and Methods: A total of 285 chronic ITP patients (187 women, 65.6%; 98 men, 34.4%) followed in 55 centers were enrolled in this retrospective cohort. Response to treatment was assessed according to platelet count (/mm3) and defined as complete (platelet count of >100,000/mm3), partial (30,000-100,000/mm3 or doubling of platelet count after treatment), or unresponsive (<30,000/mm3). Clinical findings, descriptive features, response to treatment, and side effects were recorded. Correlations between descriptive, clinical, and hematological parameters were analyzed. Results: The median age at diagnosis was 43.9±20.6 (range: 3-95) years and the duration of follow-up was 18.0±6.4 (range: 6-28.2) months. Overall response rate was 86.7% (n=247). Complete and partial responses were observed in 182 (63.8%) and 65 (22.8%) patients, respectively. Thirty-eight patients (13.4%) did not respond to eltrombopag treatment. For patients above 60 years old (n=68), overall response rate was 89.7% (n=61), and for those above 80 years old (n=12), overall response rate was 83% (n=10). Considering thrombocyte count before treatment, eltrombopag significantly increased platelet count at the 1st, 2nd, 3rd, 4th, and 8th weeks of treatment. As the time required for partial or complete response increased, response to treatment was significantly reduced. The time to reach the maximum platelet levels after treatment was quite variable (1-202 weeks). Notably, the higher the maximum platelet count after eltrombopag treatment, the more likely that side effects would occur. The most common side effects were headache (21.6%), weakness (13.7%), hepatotoxicity (11.8%), and thrombosis (5.9%). Conclusion: Results of the current study imply that eltrombopag is an effective therapeutic option even in elderly patients with chronic ITP. However, patients must be closely monitored for response and side effects during treatment. Since both response and side effects may be variable throughout the follow-up period, patients should be evaluated dynamically, especially in terms of thrombotic risk factors.

The Turkish experience with therapeutic plasma exchange: A national survey.

Therapeutic plasma exchange (TPE) is used to treat more than 60 diseases worldwide and has drawn growing interest. Little is known about the current situation of TPE activity in Turkey, so we developed a survey to obtain information about this timely topic. We collected data on TPE from 28 apheresis units throughout Turkey. We performed a total of 24,912 TPE procedures with 3203 patients over the past decade. Twenty years ago, the majority of procedures were performed for neurological and hematological disorders, and today, most TPE procedures are done for the same reasons. The only historical change has been an increase in TPE procedures in renal conditions. Currently, renal conditions were more frequently an indication for TPE than rheumatic conditions. Fresh frozen plasma was the most frequently used replacement fluid, followed by 5% albumin, used in 57.9% and 34.6% of procedures, respectively. The most frequently used anticoagulants in TPE were ACD-A and heparin/ACD-A, used with 1671 (52.2%) and 1164 (36.4%) patients, respectively. The frequency of adverse events (AEs) was 12.6%. The most common AEs were hypocalcemia-related symptoms, hypotension, and urticaria. We encountered no severe AEs that led to severe morbidity and mortality. Overall, more than two thirds of the patients showed improvement in the underlying disease. Here, we report on a nationwide survey on TPE activity in Turkey. We conclude that there has been a great increase in apheresis science, and the number of TPE procedures conducted in Turkey has increased steadily over time. Finally, we would like to point out that our past experiences and published international guidelines were the most important tools in gaining expertise regarding TPE.

The Incidence and Predictive Factors in the Development of Acute Hepatitis in Patients with Leukemia.

INTRODUCTION: Liver involvement is common in hematological malignancies, but the incidence and pattern of liver injury vary among the different types. The aims of our study were to determine the incidence and clinical course of acute hepatitis and the important factors for its development in patients with leukemia after chemotherapy. MATERIALS AND METHODS: All patients with the diagnosis of leukemia who were treated at the Department of Hematology between January 2008 and January 2013 were included in the study. A detailed medical history, clinical and laboratory findings, treatment modalities, complications, and clinical course were recorded retrospectively. RESULTS: A total of 124 patients (64 females) with the diagnosis of leukemia were included in the study. The mean age was 45.2 years (16-89 years) and mean follow-up time was 29.7 months (0.25-192 months). A total of 43 (34.6%) patients had acute hepatitis after chemotherapy. Pattern of liver injury was hepatocellular in 31 patients, cholestasis in 2, and mix in 10 patients. Age (p = 0.001), hepatitis B surface antigen (HBsAg, p = 0.007), acute leukemia (p < 0.001), positive blood culture (p = 0.004), the amount of transfused red blood cell (p = 0.001), and amount of transfused platelets (p = 0.002) were significantly different under univariate analysis between the acute hepatitis group and the nonacute hepatitis group. Under multivariate analysis, only acute lymphoblastic leukemia (ALL) was identified as independent predictive factor for development of acute hepatitis after starting chemotherapy. CONCLUSION: Acute and self-limited hepatitis develops in the substantial proportion of patients with leukemia. The most important factor for development of acute hepatitis is the type of leukemia.How to cite this article: Kaya M, Akdogan R, Uçmak F, Ayyildiz MO, Karakus A, Kaplan MA. The Incidence and Predictive Factors in the Development of Acute Hepatitis in Patients with Leukemia. Euroasian J Hepato-Gastroenterol 2018;8(1):31-37.

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.

Efficacy of CLARA in recurrent/refractory acute myeloid leukaemia patients unresponsive to FLAG chemotherapy.

We hereby report our multicentre, retrospective experience with CLARA in patients with fludarabine/cytarabine/G-CSF (FLAG) refractory AML. The study included all consecutive R/R AML patients, who received CLARA salvage during October 2010-October 2015 period. All patients were unresponsive to FLAG salvage chemotherapy regimen and did not undergo previous allo-HCT. A total of 40 patients were included. Following CLARA 5 (12.5%) patients experienced induction mortality and 10 (25%) patients achieved CR. 25 (62.5%) patients were unresponsive to CLARA. 7 (17.5%) out of 10 patients in CR received allo-HCT. Median overall survival of patients who achieved CR after CLARA was 24.5 months (8.5-54.5) and 3 months (2.5-5), in patients who underwent and didn't allo-HCT, respectively. Our results indicate that CLARA may be good alternative even in FLAG refractory AML patients and can be used as a bridge to allo-HCT, who have a suitable donor and able to tolerate the procedure.

Assessment of the underlying causes of the immune thrombocytopenia: Ten years experience.

OBJECTIVE: Immune thrombocytopenia (ITP) is an immune haematologic disorder causing platelet destruction mediated by anti-platelet antibodies. In this study we aimed to evaluate the clinical and laboratory variables of ITP patients in southeast of Turkey. METHODS: In this retrospective study 167 ITP patients between 2005 and 2015 were evaluated. All patients were screened for immunological parameters including ANA (antinuclear antibodies), anti dsDNA (anti-double-stranded-DNA), ACA(anti-cardiolipin) IgM and IgG, LA (lupus anticoagulants). All patients were screened for Helicobacter pylori, HBsAg (Hepatitis B surface antigen), anti-HCV (hepatitis C virus antibody), and anti-HIV ½ (HIV antibody) and brucellosis.. RESULTS: Among the patients, 50 (29.9%) patients were male, 117 (70.1%) were female. The age range of patients was 18-86 (mean 38.16±14). In 56 patients (33.5%) splenectomy was performed. 36 patients (21.6%) were positive for ANA, 5 (3%) were positive for anti dsDNA, 14 (8.4%) for ACA Ig G, and 14 (8.4%) patients for ACA IgM. LA was tested in 165 patients and 30 (18%) patients were positive for LA. Microbiologic evaluation was as follows: 16 patients (9.6%) were positive for HbsAg, 109 (65.3%) positive for Anti-HBs, 5 positive for anti-HCV (3%), 56 (33.5%) patients were positive for Helicobacter pylori antigen, 5 (2.9%) for Brucella and one patient was positive for anti-HIV ½. CONCLUSIONS: Immune thrombocytopenia patients have to be evaluated according to their demographic characteristics and laboratory results. Secondary causes of ITP were HIV, HCV, Helicobacter pylori, brucellosis, tuberculosis, and autoimmune diseases in our region. Management of ITP patients can change in different regions.

Presentation and Management of Paroxysmal Nocturnal Hemoglobinuria: A Single-Center Experience.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired disorder characterized by intravascular hemolysis. Real-world experience of PNH management is largely unreported. A retrospective analysis was undertaken based on medical records from six patients with PNH [two with aplastic anemia (AA)] treated at our center, Dicle University, Turkey. Diagnosis was based on granulocyte PNH clones, ranging from 93% to 66%. All patients had symptoms consistent with PNH. One patient was managed adequately with supportive measures only. Five were treated with the complement inhibitor eculizumab. Follow-up data (<1 year) were available in four cases (the fifth had received only three infusions by final follow-up). Hemoglobin level in these four patients increased from 4.1-7.2 g/dL to 8.3-13.0 g/dL. Lactate dehydrogenase, a marker for hemolysis, decreased profoundly in the two non-AA patients, with more minor improvements in the two AA patients. Weakness and fatigue improved in all eculizumab-treated patients. Four of the five treated patients became transfusion independent, including the patient given only three infusions. In the remaining case, a patient with AA, transfusion requirement decreased, and abdominal pain and dysphagia resolved. No adverse events occurred. PNH can be successfully managed in routine practice.

Cisplatin-based therapy for the treatment of elderly patients with non-small-cell lung cancer: a retrospective analysis of a single institution.

BACKGROUND: In spite of the fact that platinum-based doublets are considered the standard therapy for patients with advanced non-small-cell lung cancer (NSCLC), no elderly-specific platinum based prospective phase III regimen has been explored. The aim of this retrospective singlecenter study was to evaluate the efficacy and side effects of cisplatin-based therapy specifically for the elderly. METHODS: Patients receiving platinum-based treatment were divided into three groups. In the first group (GC), Gemcitabine was administrated at 1000 mg/m2 on days 1, 8 and cisplatin was added at 75 mg/m2 on day 1. In the second group (DC), 75 mg/m2 docetaxel and cisplatin were administered on day 1. The third group (PC) received 175 mg of paclitaxel and 75 mg of cisplatin on day 1. These treatments were repeated every three weeks. RESULT: GC arm had 36, the DC arm 42 and the PC arm 29 patients. Grade III-IV thrombocytopenia was higher in the GC arm (21.2% received GC, 2.8% received DC, and 3.8% received PC), while sensory neuropathy was lower in patients with GC arm (3.0%, 22.2%, and 23.1% received GC, DC and PC, respectively). There were no statistically significant difference in the response rates among the three groups (p>0.05). The median Progression-free survival (PFS) was 5.0 months and the median Overall survival (OS) in each group was 7.1, 7.4 and 7.1 months, respectively (p>0.05). CONCLUSION: The response rate, median PFS and OS were similar among the three treatment arms. Grade III-IV thrombocytopenia was higher in the GC arm, while the GC regimen was more favorable than the other cisplatin-based treatments with regard to sensory neuropathy.

Prognostic factors for second-line treatment of advanced non-small-cell lung cancer: retrospective analysis at a single institution.

BACKGROUND: Platinum-based chemotherapy for advanced non-small cell lung cancer (NSCLC) is still considered the first choice, presenting a modest survival advantage. However, the patients eventually experience disease progression and require second-line therapy. While there are reliable predictors to identify patients receiving first-line chemotherapy, very little knowledge is available about the prognostic factors in patients who receive second-line treatments. The present study was therefore performed. METHODS: We retrospectively reviewed 107 patients receiving second-line treatments from August 2002 to March 2012 in the Dicle University, School of Medicine, Department of Medical Oncology. Fourteen potential prognostic variables were chosen for analysis in this study. Univariate and multivariate analyses were conducted to identify prognostic factors associated with survival. RESULT: The results of univariate analysis for overall survival (OS) were identified to have prognostic significance: performance status (PS), stage, response to first-line chemotherapy, response to second- line chemotherapy and number of metastasis. PS, diabetes mellitus (DM), response to first-line chemotherapy and response to second-line chemotherapy were identified to have prognostic significance for progression-free survival (PFS). Multivariate analysis showed that PS, response to first-line chemotherapy and response to second- line chemotherapy were considered independent prognostic factors for OS. Furthermore, PS and response to second-line chemotherapy were considered independent prognostic factors for PFS. CONCLUSION: In conclusion, PS, response to first and second-line chemotherapy were identified as important prognostic factors for OS in advanced NSCLC patients who were undergoing second-line palliative treatment. Furthermore, PS and response to second-line chemotherapy were considered independent prognostic factors for PFS. It may be concluded that these findings may facilitate pretreatment prediction of survival and can be used for selecting patients for the correct choice of treatment.

Is diabetes mellitus a prognostic factor for survival in patients with small cell lung cancer?

BACKGROUND: Previous studies have pointed to many different prognostic factors for small cell lung cancer (SCLC) but diabetes mellitus (DM) has not been clearly or consistently identified as of prognostic value. The aim of this study was to investigate the prognostic significance of the characteristics of patients and clinical laboratory tests in SCLC. Specifically, we investigated that the impact of DM for survival in the patients receiving first-line etoposide plus cisplatin (EP) chemotherapy. METHODS: We retrospectively reviewed 161 patients with SCLC with a focus on DM and other potential prognostic variables were chosen for univariate and multivariate analyses with respect to survival. RESULT: Among the sixteen variables of univariate analysis, five were identified to have prognostic significance: performance status (PS) (p <0.001), stage (p=0.001), DM (p=0.005), serum albumin (p <0.001) and hemoglobin levels (p=0.03). Multivariate analysis showed PS, stage and serum albumin level to be independent prognostic factors for survival (p=0.02, p=0.02 and p=0.009 respectively), but DM was not an independnet factor. CONCLUSION: In conclusion, PS, stage and serum albumin level were identified as important prognostic factors, while DM at the time of diagnosis of SCLC did not have prognostic importance for survival.