Multiple Nervous System Involvement of Erdheim-Chester Disease With Responsive Perinephritic Hypermetabolism.

ABSTRACT: A 36-year-old man who was at follow-up for histiocytosis had sudden-onset symptoms of unilateral ophthalmic increased pressure. The patient was referred to the FDG PET/CT for determination of involvement with suspicion of Erdheim-Chester disease. The reduction of the FDG uptake in all of the lesions (medial temporal lobes, nasal septum, medulla spinalis in sacral region, as well as perinephritic infiltrations), which were determined by the first PET/CT, was achieved at second imaging.

Glofitamab in relapsed/refractory diffuse large B-cell lymphoma: Real-world data.

Glofitamab is a CD3xCD20 bi-specific antibody with two fragments directed to the CD20 antigen and a single CD3-binding fragment. Encouraging response and survival rates were recently reported in a pivotal phase II expansion trial conducted in patients with relapsed/refractory (R/R) B-cell lymphoma. However, the real-world data of patients of all ages with no strict selection criteria are still lacking. Herein, this retrospective study aimed to evaluate the outcomes of diffuse large B-cell lymphoma (DLBCL) patients who received glofitamab via compassionate use in Turkey. Forty-three patients from 20 centers who received at least one dose of the treatment were included in this study. The median age was 54 years. The median number of previous therapies was 4, and 23 patients were refractory to first-line treatment. Twenty patients had previously undergone autologous stem cell transplantation. The median follow-up time was 5.7 months. In efficacy-evaluable patients, 21% and 16% of them achieved complete response and partial response, respectively. The median response duration was 6.3 months. The median progression-free survival (PFS) and overall survival (OS) was 3.3 and 8.8 months, respectively. None of the treatment-responsive patients progressed during the study period, and their estimated 1-year PFS and OS rate was 83%. The most frequently reported toxicity was hematological toxicity. Sixteen patients survived, while 27 died at the time of the analysis. The most common cause of death was disease progression. One patient died of cytokine release syndrome during the first cycle after receiving the first dose of glofitamab. Meanwhile, two patients died due to glofitamab-related febrile neutropenia. This is the largest real-world study on the effectiveness and toxicity of glofitamab treatment in R/R DLBCL patients. The median OS of 9 months seems promising in this heavily pretreated group. The toxicity related mortality rates were the primary concerns in this study.

Survival in rhino-orbito-cerebral mucormycosis: An international, multicenter ID-IRI study.

BACKGROUND: Mucormycosis is an emerging aggressive mold infection. This study aimed to assess the outcome of hospitalized adults with rhino-orbito-cerebral mucormycosis (ROCM). The secondary objective was to identify prognostic factors in this setting. METHODS: This study was an international, retrospective, multicenter study. Patients' data were collected from 29 referral centers in 6 countries. All qualified as "proven cases" according to the EORTC/MSGERC criteria. RESULTS: We included 74 consecutive adult patients hospitalized with ROCM. Rhino-orbito-cerebral type infection was the most common presentation (n = 43; 58.1%) followed by rhino-orbital type (n = 31; 41.9%). Twenty (27%) had acquired nosocomial bacterial infections. A total of 59 (79.7%) patients (16 in combination) received appropriate antifungal treatment with high-doses of liposomal amphotericin B. Fifty-six patients (75.7%) underwent curative surgery. Thirty-five (47.3%) required intensive care unit admission (27; 36.5% under mechanical ventilation). Hospital survival was 56.8%, being reduced to 7.4% in patients with invasive mechanical ventilation. A multivariate binary backward logistic regression model identified confusion at admission (OR 11.48), overlapping hospital-acquired infection (OR 10.27), use of antifungal treatment before diagnosis (OR 10.20), no surgical debridement (OR 5.92), and the absence of prior sinusitis (OR 6.32) were independently associated with increased risk for death. CONCLUSION: Today, ROCM still has high mortality rate. Improving source control, rational therpy, and preventing nosocomial infections may improve survival in this severe infection.

Ruxolitinib Reduces Oxidative Stress in Patients With Primary Myelofibrosis: A Multicenter Study.

Introduction Primary myelofibrosis (PM) has a lower overall survival rate than other myeloproliferative neoplasms, and leukemic transformation is the most common cause of death. Increased oxidative stress has an important role in leukemic transformation in these patients. In this study, we aimed to find an answer to the question, "Could Ruxolitinib, which has been widely used in patients with myelofibrosis in recent years, have a role in reducing oxidative stress in these patients?". Methods A total of 106 patients with PM and 111 healthy volunteers were included in this study. We collected the serum samples of healthy volunteers and patients with myelofibrosis at the time of diagnosis and one month after the initiation of Ruxolitinib treatment. Ischemia modified albumin (IMA), native thiol, total thiol, and disulfide levels were studied. The disulfide/native thiol, disulfide/total thiol, and native thiol/total thiol ratios were calculated. Results IMA, native thiol, total thiol, disulfide levels, disulfide/native thiol, and disulfide/total thiol ratios at the time of diagnosis were significantly different in patients with myelofibrosis compared to the control group (p=0.001). Ruxolitinib significantly reduced oxidative stress when the measurements in the first month after Ruxolitinib were compared with those at the time of diagnosis (p=0.001). In patients with ASXL1 mutation, intermediate-2 risk, and high-risk according to the Dipps-plus score, the decrease in oxidative stress in the first month of treatment was more significant than at the time of diagnosis. Conclusion Ruxolitinib may be an effective treatment for reducing oxidative stress in patients with PM. The reduction in oxidative stress parameters with treatment in patients with ASXL1 mutation, intermediate-2, and high-risk patients was observed to be higher.

Integration of low muscle mass into the IPS system and its prognostic significance in patients with Hodgkin's lymphoma.

Aim: The aim of this study is to determine whether a novel prognostic score can be obtained by including low muscle mass in the international prognostic score (IPS) system. Materials & Methods: Psoas muscle areas were determined in the PET/CT scans of the patients taken for staging at the time of diagnosis and after two cycles of ABVD. After evaluating the effect of low muscle mass on overall survival, receiver operating characteristic (ROC) analyzes were performed by including it in IPS systems. Results: Overall survival was significantly lower in patients with low muscle mass. Adding low muscle mass to IPS scores increased AUC, sensitivity and specificity. Conclusion: The integration of low muscle mass into the IPS scoring systems increased the success of these systems in predicting a prognosis.

Lay abstract Hodgkin's lymphoma is a cancer that responds well to standard treatments. However, the cancer recurs 30% of the time. Improved scoring systems could help better predict the outcomes of treatment. The 'International Prognostic Score' (IPS) system is an algorithm currently used to predict the possibility of death and treatment complications. In this study, low muscle mass is evaluated as data that could be added to the current scoring system to improve the system's ability to predict outcomes. Data from the scans of patients before and after treatment were used to determine the muscle mass. It was found that survival was significantly lower in patients with low muscle mass. This suggests that this information is highly effective in predicting the outcomes of Hodgkin's lymphoma patients.

Thiol/Disulfide Balance in Older Patients with BCR-ABL Negative Myeloproliferative Neoplasms.

BACKGROUND: The trio Essential Thrombocytosis (ET), Polycythemia Vera (PV), and Primary Myelofibrosis (PM) are BCR-ABL negative myeloproliferative neoplasms. All three diseases have the risk of transforming into acute leukemia. Oxidative stress and some genetic mutations increase the risk of leukemic transformation. The median age in patients with ET, PV, and MF is around 64 years, and it is expected to exceed 65 in the coming years. Since oxidative stress increases with age, we aimed to evaluate the oxidative stress parameters in older patients with myeloproliferative neoplasms. METHODS: The study included a total of 160 patients (57 patients with Essential Thrombocytosis, 52 patients with Primary Myelofibrosis, and 51 patients with Polycythemia Vera) and 56 healthy controls, aged 65 and over. Ischemia Modified Albumin (IMA) and thiol parameters (native thiol, total thiol, and disulfide) were studied from serum samples taken at the time of diagnosis. RESULTS: The median age of the patients was 69 (65 - 85) years. Patients had higher levels of IMA and lower levels of thiol compared to the control group (p < 0.001). When evaluated according to disease subgroups, it was observed that the highest IMA levels and the lowest thiol levels were in patients with PM (p < 0.001). Higher IMA levels and lower native thiol levels were found in patients with the ASXL1 mutation (p < 0.001). CONCLUSIONS: Serum IMA and thiol levels are also significantly changed in older patients with BCR-ABL negative myeloproliferative neoplasia. Changes in these markers are independent of age. Disease-associated mutations such as ASXL1 can also affect the serum levels of these markers.

An investigation of the relation between catalase C262T gene polymorphism and catalase enzyme activity in leukemia patients.

INTRODUCTION: Catalase (CAT), an antioxidant enzyme, catalyzes conversion of hydrogen peroxide to water and molecular oxygen, protecting cells against oxidative stress. The aim of this study was to investigate the possible association between CAT C262T polymorphism in the promoter region of the CAT gene and leukemia risk and to determine the relationship between CAT genotypes and CAT enzyme activities. MATERIAL AND METHODS: Genotypes of 102 cases and 112 healthy controls' genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism methods. Catalase activity was measured with the method of Aebi. RESULTS: The frequencies of the T allele among the cases and controls were 28.4% and 25.9%, respectively (p = 0.75). The frequencies of CC, CT, and TT among cases were 57.8%, 27.4%, and 14.7%, respectively, while in controls, the frequencies of CC, CT, and TT were 54.4%, 39.3%, and 6.3%, respectively, which were not significantly different. Although CAT enzyme activity was lower in leukemia patients with TT genotypes than in controls, this did not reach statistical significance (p = 0.37). CONCLUSIONS: This is the first report showing that CAT C262T polymorphism is not a genetic predisposing factor for the risk of leukemia in the Turkish population. However, additional research is needed to confirm these findings.

Efficacy and Safety of Ibrutinib Therapy in Patients with Chronic Lymphocytic Leukemia: Retrospective Analysis of Real-Life Data

Objective: This study aimed to retrospectively evaluate the efficacy, safety, and survival outcome of single-agent ibrutinib therapy in chronic lymphocytic leukemia patients. Materials and Methods: A total of 136 patients (mean age ± standard deviation: 64.6±10.3 years, 66.9% males) who had received at least one dose of ibrutinib were included in this retrospective multicenter, noninterventional hospital-registry study conducted at 33 centers across Turkey. Data on patient demographics, baseline characteristics, laboratory findings, and leukemia-cell cytogenetics were retrieved. Treatment response, survival outcome including overall survival (OS) and progression-free survival (PFS), and safety data were analyzed. Results: Overall, 36.7% of patients were categorized as Eastern Cooperative Oncology Group (ECOG) class 2-3, while 44.9% were in Rai stage 4. Fluorescence in situ hybridization revealed the presence of del(17p) in 39.8% of the patients. Patients received a median of 2.0 (range: 0-7) lines of pre-ibrutinib therapy. Median duration of therapy was 8.8 months (range: 0.4-58.0 months). The 1-year PFS and OS rates were 82.2% and 84.6%, respectively, while median PFS time was 30.0 (standard error, 95% confidence interval: 5.1, 20.0-40.0) months and median OS time was 37.9 (3.2, 31.5-44.2) months. Treatment response (complete or partial response), PFS time, and OS time were better with 0-2 lines versus 3-7 lines of prior therapy (p<0.001, p=0.001, and p<0.001, respectively), with ECOG class 0-1 versus class 2-3 (p=0.006, p=0.011, and p=0.001, respectively), and with Rai stage 0-2 versus 3-4 (p=0.002, p=0.001, and p=0.002, respectively). No significant difference was noted in treatment response rates or survival outcome with respect to the presence of comorbidity, bulky disease, or del(17p). While 176 adverse events (AEs) were reported in 74 (54.4%) patients, 46 of those 176 AEs were grade 3-4, including pneumonia (n=12), neutropenia (n=11), anemia (n=5), thrombocytopenia (n=5), and fever (n=5). Conclusion: This real-life analysis confirms the favorable efficacy and safety profile of long-term ibrutinib treatment while emphasizing the potential adverse impacts of poorer ECOG performance status, heavy treatment prior to ibrutinib, and advanced Rai stage on patient compliance, treatment response, and survival outcomes.

Cardiac Chamber Quantification by Echocardiography in Adults With Sickle Cell Disease: Need Attention to Eccentric Hypertrophy.

Introduction and aim Sickle cell anemia (SCA) is the most common hemoglobinopathy worldwide, and cardiovascular diseases are the most common causes of death. In these patients, cardiac remodeling begins from childhood and leads to sickle cell cardiomyopathy in the following years. Concentric hypertrophy and eccentric hypertrophy are known to predict early cardiac events. This study aims to reveal the relationship between cardiac remodeling types and survival in patients with SCA and investigate the factors that may affect left ventricular mass. Materials and methods A total of 146 patients with SCA were included in the study, and the left ventricular mass index (LVMI) and relative wall thickness (RWT) of the patients were calculated according to echocardiographic measurements, and the patients were categorized into normal, concentric remodeling (CR), concentric hypertrophy (CH), and eccentric hypertrophy (EH) groups. Results The median age of the patients is 32 (18-72). In logistic regression analysis, hemoglobin S (HbS) and ferritin levels were independent predictors for LVMI (p = 0.01 and p < 0.001, respectively). It was observed that 56 (38.4%) of the patients had normal left ventricles, 24 (16.4%) had CR, 21 (14.4%) had CH, and 45 (30.8%) had EH. 31 (21.2%) of the patients died. When we look at the survival curves, there was a statistically significant difference between the four groups (log-rank p < 0.001). It was observed that patients with EH were the group with the lowest probability of survival. Conclusion Cardiac death is one of the most common causes of death in patients with SCA. Early detection of cardiac disorders and starting treatment may be important in reducing mortality in these patients.

Evaluation of clinical characteristics of patients with paroxysmal nocturnal hemoglobinuria treated with eculizumab in Turkey: a multicenter retrospective analysis.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare X-linked genetic disorder. On the contrary to its name, it is a multisystemic disease and various symptoms other than hemoglobinuria could be occurred. It could be life threatening especially because of thromboembolic events. In the last decade, a terminal complement inhibition with eculizumab approved with promising results for PNH patients. We conducted this study to evaluate the long term experience of eculizumab therapy from Turkey for the first time. Our cohort included 138 patients with PNH treated with eculizumab between January 2008 and December 2018 at 28 centers in Turkey. Laboratory and clinical findings at the time of diagnosis and after eculizumab therapy were recorded retrospectively. The median age was 39 (range 18-84) years and median granulocyte PNH clone size was 74% (range 3.06-99.84%) at the time of diagnosis. PNH with bone marrow failure syndrome was detected in 49 patients and the rest of 89 patients had classical PNH. Overall 45 patients (32.6%) had a history of any prior thrombotic event before eculizumab therapy and only 2 thrombotic events were reported during the study period. Most common symptoms are fatigue (75.3%), hemoglobinuria (18.1%), abdominal pain (15.2%) and dysphagia (7.9%). Although PNH is commonly related with coombs negativity, we detected coombs positivity in 2.17% of patients. Seven months after the therapy, increased hemoglobin level was seen and remarkably improvement of lactate dehydrogenase level during the treatment was occurred. In addition to previous studies, our real life data support that eculizumab is well tolerated with no serious adverse events and improves the PNH related findings.

Comparison of the clinical course of COVID-19 infection in sickle cell disease patients with healthcare professionals.

It is highly expected that COVID-19 infection will have devastating consequences in sickle cell disease (SCD) patients due to endothelial activation and decreased tissue and organ reserve as a result of microvascular ischemia and continuous inflammation. In this study, we aimed to compare the clinical course of COVID-19 in adult SCD patients under the organ injury mitigation and clinical care improvement program (BASCARE) with healthcare professionals without significant comorbid conditions. The study was planned as a retrospective, multicenter and cross-sectional study. Thirty-nine SCD patients, ages 18 to 64 years, and 121 healthcare professionals, ages 21 to 53, were included in the study. The data were collected from the Electronic Health Recording System of PRANA, where SCD patients under the BASCARE program had been registered. The data of other patients were collected from the Electronic Hospital Data Recording System and patient files. In the SCD group, the crude incidence of COVID-19 was 9%, while in healthcare professionals at the same period was 23%. Among the symptoms, besides fever, loss of smell and taste were more prominent in the SCD group than in healthcare professionals. There was a significant difference between the two groups in terms of development of pneumonia, hospitalization, and need for intubation (43 vs 5%, P < 0.00001; 26 vs 7%, P = 0.002; and 10 vs 1%, P = 0.002, respectively). Prophylactic low molecular weight heparin and salicylate were used more in the SCD group than in healthcare professionals group (41 vs 9% and 28 vs 1%; P < 0.0001 for both). The 3-month mortality rate was demonstrated as 5% in the SCD group, while 0 in the healthcare professionals group. One patient in the SCD group became continously dependent on respiratory support. The cause of death was acute chest syndrome in the first case, hepatic necrosis and multi-organ failure in the second case. In conclusion, these observations supported the expectation that the course of COVID-19 in SCD patients will get worse. The BASCARE program applied in SCD patients could not change the poor outcome.

Sevuparin for the treatment of acute pain crisis in patients with sickle cell disease: a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial.

BACKGROUND: There are no approved treatments for vaso-occlusive crises in sickle cell disease. Sevuparin is a novel non-anticoagulant low molecular weight heparinoid, with anti-adhesive properties. In this study, we tested whether sevuparin could shorten vaso-occlusive crisis duration in hospitalised patients with sickle cell disease. METHODS: We did a multicentre, double-blinded, placebo-controlled, phase 2 study in 16 public access clinical hospitals in the Netherlands, Lebanon, Turkey, Bahrain, Oman, Saudi Arabia, and Jamaica. Patients aged 12-50 years with a diagnosis of sickle cell disease (types HbSS, HbSC, HbSß0-thalassaemia, or HbSß+-thalassaemia) on a stable dose of hydroxyurea, hospitalised with vaso-occlusive crisis for parenteral opioid analgesia with a projected stay of more than 48 h were included in the study. Patients were randomly assigned (1:1) using a computer-generated randomisation scheme to receive sevuparin (18 mg/kg per day) or placebo (NaCl, 0·9% solution) intravenously for 2-7 days until vaso-occlusive crisis resolution. All individuals involved in the trial were masked to treatment allocation. The analysis was done in the intention-to-treat population. The primary endpoint was time to vaso-occlusive crisis resolution defined as freedom from parenteral opioid use (in preceding 6-10 h); and readiness for discharge as judged by the patient or physician. The trial is registered with ClinicalTrials.gov, NCT02515838. FINDINGS: Between Oct 7, 2015, and Feb 10, 2019, 144 patients were randomly assigned and administered sevuparin (n=69) or placebo (n=75). The median age was 22·2 years (range 12·2-33·6), 104 (72%) 144 were adults (18 years or older), and 90 (63%) were male and 54 (37%) were female. The intention-to-treat analysis for the primary endpoint showed no significant difference in median time to vaso-occlusive crisis resolution between the sevuparin and placebo groups (100·4 h [95% CI 85·5-116·8]) vs 86·4 h [70·6-95·1]; hazard ratio 0·89 [0·6-1·3]; p=0·55). Serious adverse events occurred in 16 (22%) of 68 patients in the sevuparin group and in 21 (22%) of patients in the placebo group. The most frequent treatment-emergent adverse events were pyrexia (17 [25%] in the sevuparin group vs 17 [22%] in the placebo group), constipation (12 [18%] vs 17 [22%]), and decreased haemoglobin (18 [26%] vs 9 [12%]). There were no deaths in the sevuparin group and there was one (1%) death in the placebo group after a hyper-haemolytic episode due to alloimmunisation. INTERPRETATION: This result, as well as the results seen in other clinical studies of inhibitors of adhesion in sickle cell disease, suggest that selectin-mediated adhesion might be important in the initiation, but not maintenance of vaso-occlusion, indicating that strategies to treat vaso-occlusive crises differ from strategies to prevent this complication. FUNDING: Modus Therapeutics.

Is dynamic thiol/disulfide homeostasis associated with the prognosis of myelodysplastic syndrome?

BACKGROUND: This study planned to investigate the relationship of dynamic thiol/disulfide homeostasis with the prognosis of myelodysplastic syndrome (MDS). METHODS: 80 patients who had been diagnosed with MDS between 2012 and 2017 and who were older than 18 were included in the study together with 80 healthy control subjects. The MDS diagnosis was confirmed using bone marrow aspiration-biopsy immunostaining. Dynamic thiol/disulfide homeostasis and ischemia-modified albumin (IMA) levels were examined. RESULTS: The average IMA (0.71±0.08 vs. 0.67±0.09; p=0.002), median disulfide (18.0 vs. 11.6; p<0.001), median disulfide/native thiol (6 vs. 3; p<0.001), and median disulfide/total thiol (5.4 vs. 2.9; p<0.001) were found higher in the MDS patients compared to control group, and the median hemoglobin, median white blood cell count, median neutrophil count, median lymphocyte count, average native thiol (290.7±48.5 vs. 371.5±103.8; p<0.001), average total thiol (328.2±48.9 vs. 393±105.5; p<0.001), and average native thiol/total thiol (%) (88.3±4.3 vs. 94.2±2.1; p<0.001) were found to below. Risk factors such as collagen tissue disease (HR:9.17; p=0.005), MDS-EB-1 (HR:10.14; p=0.032), MDS-EB-2 (HR:18.2; p=0.043), and disulfide/native thiol (HR:1.17; p=0.023) were found as the independent predictors anticipating progression to acute myeloid leukemia. In the Cox regression model, risk factors such as age (HR:1.05; p=0.002), MDS-EB-1 (HR:12.58; p<0.001), MDS-EB-2 (HR:5.75; p=0.033), disulfide/native thiol (HR:1.14; p=0.040), and hemoglobin (HR:0.64; p=0.007) were found as predictors anticipating for mortality. CONCLUSIONS: We can argue that dynamic thiol/disulfide homeostasis could have significant effects on both the etiopathogenesis and the survival of patients with MDS, and it could be included in new prognostic scoring systems.

Study for the Diagnostic Screening of Paroxysmal Nocturnal Hemoglobinuria in Older Patients with Unexplained Anemia and/or Cytopenia.

BACKGROUND: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired hematopoietic stem cell disease that may lead to weakness and death of patients, if unrecognized and untreated. Although consensus guidelines were reviewed recently for the diagnostic screening of PNH with multi-parameter flow cytometry (FCM), until now, no study has investigated the efficiency of such clinical indications in older patients. METHODS: Overall, 20 centers participated in the study and a total of 1,689 patients were included, 313 of whom were at geriatric age and 1,376 were aged 18 - 64 years. We evaluated the efficiency of consensus clinical indications for PNH testing using FCM in peripheral blood samples and compared the results of older patients and patients aged 18 - 64 years. RESULTS: PNH clones were detected positive in 7/313 (2.2%) of the older patients. Five (74.4%) of the patients with PNH clones had aplastic anemia, 1 had unexplained cytopenia, and 1 patient had myelodysplastic syndrome (MDS) with refractory anemia. PNH clones were not detected in any older patients who were screened for unexplained thrombosis, Coombs (-) hemolytic anemia, hemoglobinuria, and others (e.g., elevated lactate dehydrogenase (LDH), splenomegaly). We detected PNH clones in 55/1376 (4%) samples of the patients aged under 65 years. Forty-two (76.4%) patients with PNH clones had aplastic anemia, 2 patients had Coombs (-) hemolytic anemia, 3 patients had unexplained cytopenia, 1 patient had MDS with refractory anemia, 1 patient had hemoglobinuria, and 6 (10.9%) had others (e.g., elevated LDH, splenomegaly). PNH clones were not detected in any patients who were screened for unexplained thrombosis. There was no statistical difference between the geriatric population and patients aged 18 - 64 years in terms of clinical indications for PNH screening with FCM (p = 0.49). CONCLUSIONS: Our results showed that the current clinical indications for PNH screening with FCM were also efficient in older patients. We suggest that older patients with unexplained anemia, myelodysplastic syndrome with refractory anemia, and unexplained cytopenia should be screened for PNH with FCM to identify patients who would benefit from treatment.

Receptor Activator of Nuclear Factor κ-Β Ligand/Osteoprotegerin Axis in Adults with Hb S/ß-Thalassemia and ß-Thalassemia Trait.

There is not enough data about osteoporosis and the role of receptor activator of nuclear factor κ-Β ligand (RANKL)/serum osteoprotegerin (OPG) system in patients with double heterozygosity for sickle cell disease and ß-thalassemia [Hb S (HBB: c.20A>T)/ß-thal] and ß-thal trait. Aim of the study was to investigate bone mineral densities (BMD) and the role of RANKL/OPG system in these cases. We studied 58 adults with Hb S/ß-thal, 52 adults with ß-thal trait, 34 healthy subjects as a control group. The BMD was determined by dual-energy X-ray absorptiometry (DEXA). Biochemical markers of bone metabolism (serum calcium, phosphorus, alkaline phosphatase, osteocalcin) parameters that affect bone metabolism (serum parathyroid hormone, thyroid-stimulating hormone, 25-hydroxyvitamin D, OPG, soluble RANKL [sRANKL]) were studied. Femoral neck Z-scores of 93.2% for ß-thal trait, 83.0% for Hb S/ß-thal patients were within the expected range. Lumbar spine Z-scores of 89.1% for ß-thal, 90.2% for Hb S/ß-thal patients were above -2.0 SD. Z-scores of the control group were within the expected range. Median serum sRANKL level was 2.80, 4.52, 5.79 pmol/L in Hb S/ß-thal, ß-thal trait, control groups, respectively (p = 0.010). Median serum OPG level was 1.07, 0.86, 0.86 pmol/L in Hb S/ß-thal, ß-thal trait, control groups, respectively (p < 0.001). ß-Thalassemia trait alone is not a risk factor for osteopenia/osteoporosis and osteoporosis does not develop in premenopausal women and men younger than 50 years with Hb S/ß-thal. However, as we determined lower levels of osteocalcin, compensatory decrease of sRANKL with compensatory increase of OPG, more severe osteoporosis may develop in advanced ages in these patient populations.

Study for the diagnostic screening of paroxsymal nocturnal hemoglobinuria in Turkey: Prospective multicentric evaluation of suspected patients.

BACKGROUND: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disease presenting with variable and various clinical findings. PNH might be overlooked and diagnosis may be delayed due to low awareness about PNH. This is the first multicenter study in Turkey, investigating the efficiency of diagnostic screening of PNH by multiparameter flow cytometry (FCM) according to consensus guidelines. METHODS: We evaluate the efficiency of consensus clinical indications for PNH testing with FCM in 1689peripheral blood samples from 20 centers between January 2014 and December 2017. RESULTS: Overall, at the 20 centers contributing to this study, PNH clone were detected in 62/1689 samples (3.6%) by FCM test. 75.8% (n = 47) of patients with PNH clone had aplastic anemia, 3.2% (n = 2) had Coombs (-) hemolytic anemia, 6.5% (n = 4) had unexplained cytopenia, 3.2% (n = 2) had MDS with refractory anemia, 1.6% (n = 1) had hemoglobinuria and 9.7% (n = 6) had others (elevated LDH, splenomegaly, etc.). In contrast, we detect no PNH clone test in patients who were screened for unexplained thrombosis. CONCLUSIONS: Our study showed that current clinical indications for PNH testing are highly efficient and diagnostic screening of suspected patients for PNH with FCM is recommended. However, advanced screening algorithms are required for patients presenting with unexplained thrombosis and normal complete blood count.

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.

Splenosis Mimicking Lymphoma Relapse Confirmed by 18F-FDG PET/CT and Tc-99m Nano-colloid Scintigraphy Thirty Years After Splenectomy for Trauma

Splenosis is implantation of the splenic tissue in the abdominal region or elsewhere in the body as a consequence of trauma or splenectomy, which might mimic intra-abdominal involvement of several malignancies. This case report presents a patient with abdominal implants without 18F-FDG accumulation confirmed to be splenosis by Tc-99m nano-coloid scintigraphy.