Evaluation of using fresh frozen plasma for patients with cirrhosis at a tertiary healthcare center in Turkey: Strict transfusion policies are essential.

AIM: Management of blood transfusions is a critical issue, especially in cirrhotic patients, because of the absence of national policies in many countries. Fresh frozen plasma (FFP) is a common blood component misused excessively in various clinical situations and cirrhosis patients without any scientific rationale. We evaluated the FFP transfusions in patients with cirrhosis at our tertiary care hospital. MATERIAL AND METHOD: The cases with cirrhosis diagnosed between 2014 and 2020 were selected using the hospital database. The appropriateness of FFP transfusion was determined based on the Practice Guidance by the American Association for the Study of Liver Diseases and Italian guidelines. RESULT: Two hundred and six liver cirrhosis patients were identified who received FFP transfusion. The median age was 63 (22-94). Of the 206 patients, 79 (38.3 %) were female, and 127 (61.7 %) were men. The most common causes of liver cirrhosis were alcohol (27.7 %). 45.6 % of the patients were in Child-Pugh Class C. We found 62.1 % of FFP replacements were inappropriately used. Most inappropriate use of FFP (22.8 %, n = 47) occurred to correct prolonged INR in the absence of bleeding. CONCLUSION: To avoid inappropriate usage of FFP, regular utilization reviews and formal education programs can be helpful. Our clinic has planned to arrange educational programs for physicians to use blood products appropriately and minimize transfusion-related side effects.

Computed tomography characteristics of multiple myeloma and other osteolytic metastatic bone lesions.

BACKGROUND: Differentiation of multiple myeloma (MM) from osteolytic metastatic (OM) bone lesions may be critical in patients with lytic bone lesions but can be challenging for radiologists. PURPOSE: To determine whether computed tomography (CT) can be used to distinguish between MM and other OM bone lesions. MATERIAL AND METHODS: In this retrospective study, 320 lesions of 207 patients diagnosed with MM or OM, based on biopsy or clinical examination, were evaluated. Eight qualitative features were evaluated by two radiologists blinded to the diagnoses. The chi-square and Fisher exact tests, and logistic regression analysis, were used to evaluate the relationships between the CT findings and diagnoses. RESULTS: High-density areas were more common in OM than MM lesions (85.2% and 19%, P < 0.001), as were perilesional sclerosis (38.9% vs. 13.2%, P < 0.001), heterogeneity (on non-contrast CT images, 60% vs. 19.1%, P < 0.001; on contrast enhanced CT images, 80.6% vs. 28.2%, P < 0.001), and ill-defined margins (34.6% vs. 9.1%, P < 0.001). Similarly, OM lesions showed high-density areas more than MM in evaluation of skeletal system subgroups (vertebrae, 93.8% vs. 29.8%, P < 0.0001; thoracic cage bones, 69.6% vs. 19.2%, P < 0.001; pelvic bones and sacrum, 84.8% vs. 7.7%, P < 0.001; peripheral skeletal bones, 81.5% vs. 8.3%, P < 0.001). Logistic regression analysis revealed that the presence of a high-density area in the lesion increased the probability of a metastasis 25.88-fold (R2 = 0.516, P < 0.001). CONCLUSION: MM and OM lesions can be differentiated by CT; OM lesions exhibit high- density areas.

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.

Prospective study of brentuximab vedotin in relapsed/refractory Hodgkin lymphoma patients who are not suitable for stem cell transplant or multi-agent chemotherapy.

Some patients with relapsed/refractory Hodgkin lymphoma (HL) are not considered suitable for stem cell transplant (SCT) and have a poor prognosis. This phase IV study (NCT01990534) evaluated brentuximab vedotin (1·8 mg/kg intravenously once every 3 weeks) in 60 patients (aged ≥18 years) with CD30-positive relapsed/refractory HL, a history of ≥1 prior systemic chemotherapy regimen, who were considered unsuitable for SCT/multi-agent chemotherapy. Primary endpoint was overall response rate (ORR) per independent review facility (IRF). Secondary endpoints included duration of response (DOR), progression-free survival (PFS) per IRF, overall survival (OS), proportion proceeding to SCT and safety. The ORR was 50%, with 12% CR; 47% proceeded to SCT. Median DOR was 4·6 months and median duration of CR was 6·1 months. After a median follow-up of 6·9 and 16·6 months, median PFS and OS were 4·8 months (95% confidence interval, 3·0-5·3) and not reached, respectively; estimated OS rate was 86% at 12 months. Most common adverse events (≥10%) were peripheral neuropathy (35%), pyrexia (18%), diarrhoea and neutropenia (each 10%). Brentuximab vedotin showed notable activity with a safety profile consistent with known toxicities, and may act as a bridge to SCT, enabling high-risk patients who achieve suboptimal response to frontline/salvage chemotherapy/radiotherapy to receive potentially curative SCT.

Can Neutrophil-to-Lymphocyte Ratio, Monocyte-to-Lymphocyte Ratio, and Platelet-to-Lymphocyte Ratio at Day +100 be used as a prognostic marker in Multiple Myeloma patients with autologous transplantation?

BACKGROUND: Recent reports have showed that neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) are predictors of progression-free survival (PFS) and overall survival (OS) in many types of cancer. This study evaluates the predictive value of NLR, MLR, and PLR for survival in MM patients treated with to ASCT. METHODS: A set of data consisting of 150 patients who underwent autologous stem cell transplantation (ASCT) for MM was collected retrospectively. The prognostic value of NLR, MLR, and PLR was investigated with Kaplan-Meier method. RESULTS: The prognostic value of NLR, MLR, and PLR was analyzed by a receiver operating characteristic (ROC) curve established to determine the cutoff. These cutoff values of NLR, PLR, and MLR were found 1.46, 86, and 0.27, respectively, on the 100th day of post-transplantation period. The overall survival (OS) and the post-transplantation OS of the patients with high NLR, MLR, and PLR levels on the 100th day of post-transplantation were shorter than the other group (P = 0.05, P = 0.018 [NLR], P = 0.05, P = 0.002 [MLR], P = 0.000, P = 0.001 [PLR]). The post-transplantation progression-free survival (PFS) of the patients with high NLR, MLR, and PLR levels on the 100th day of post-transplantation was shorter as well (P = 0.036, P = 0.001, P = 0.001, respectively). CONCLUSION: As increased NLR, MLR, and PLR predicted poor clinical outcome in MM patients with autologous transplantation in this study, they may serve as cost-effective and rapidly available prognostic biomarkers for these patients.

The Effect of Age on High-Dose Therapy with Autologous Stem Cell Support in Multiple Myeloma: A Single-Center Experience.

Background: This retrospective one-center study demonstrates the complications related to high-dose therapy with autologous stem cell support (HDT) and the survival of multiple myeloma (MM) patients according to age groups. Methods: We categorized the patients into two groups: those who were ≤65 years old (group 1) (N = 115) and those who were >65 years old (group 2) (N = 26). The mean duration of follow-up was 48 (1-125) months. Results: In group 2 patients, the use of a reduced dosage of melphalan (12 [46%] versus 30 [26%]) was more frequent in comparison to group 1 (p = 0.046). There was a statistically significant difference between the two groups regarding the neutrophil engraftment days (p = 0.001) and the median progression-free survival (PFS) (p = 0.02). The PFS was 44 months for group 1 and 30 months for group 2. There was no statistically significant difference between the groups in relation to the median duration of hospitalization, presence of bacteremia, intravenous antibiotic administration, and overall survival (OS). Conclusions: The study's results indicate that HDT is a reliable method of treatment for older patients with MM, provided that they obtain a suitable conditioning regimen and, furthermore, these patients achieved a comparable OS rate to that of younger patients.

The effect of haemoglobin, albumin, lymphocyte and platelet score on the prognosis in patients with multiple myeloma.

INTRODUCTION: In multiple myeloma cases, a variety of prognostic parameters have been identified, which contain the Durie-Salmon classification and the international staging system (ISS) that takes the serum ß2 microglobulin and albumin levels, platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), and monocyte-to-lymphocyte ratio (MLR). This study investigates the effect of haemoglobin, albumin, lymphocyte and platelet (HALP) score which is a marker of inflammation status and nutrition, at the time of diagnosis for the patients with multiple myeloma on prognosis. METHODS: A total of 200 multiple myeloma patients with HALP scores calculated from serum haemoglobin, albumin, lymphocyte count and platelet levels at the time of diagnosis were retrospectively examined. The effect of HALP score on overall survival (OS) and progression-free survival and its relationship between the previously evaluated prognostic parameters were investigated. RESULTS: The optimal cut-off value with the ROC curves for the HALP score was 28.8. The patients were divided into two groups according to the optimal value of the HALP score (low-score group: HALP ≤28.8 [n: 134] and high-score group HALP >28.8 [n: 66]). In the group with the high HALP score, the OS was statistically longer than the low HALP score group (84 months and 53 months; p = 0.0001). In addition, when the effects of NLR, PLR, HALP score and ISS stage on OS were examined by multivariate analysis, all these markers were found to be statistically significant predictors. CONCLUSIONS: HALP score may be a valuable prognostic marker for patients with multiple myeloma.

Hematopoietic recovery kinetics predicts for poor CD34+ cell mobilization after cyclophosphamide chemotherapy in multiple myeloma.

Autologous stem cell transplantation is an important part of therapy in patients with multiple myeloma. Some patients fail to collect the desired number of stem cells while others require multiple apheresis to reach the desired apheresis target. The aim of this study was to determine the predictive factors and if the hematopoietic kinetics of recovery were predictive for outcome of stem cell mobilization in cyclophosphamide + growth factor (CY-GF) mobilized patients. Three hundred and ninety six consecutive CY-GF mobilization attempts between January 2000 and December 2009 at Mayo Clinic, Rochester, MN were analyzed. Patients were divided into three groups: optimal (>5 × 10(6) CD34/kg), suboptimal (2-5 × 10(6) CD34/kg) and poor (<2 × 10(6) /kg CD34+ cells) mobilization groups. About 86% of patients had optimal stem cell collection, whereas 8% had suboptimal collection and 6% had poor (or failed) collections. Age, Hb, WBC, and platelet levels had an impact on mobilization results. Time to peripheral blood (PB) CD34+cells >10/µL predicted for efficiency of collection and the interval between recovery of WBC>1 post-CY to PB CD34+ cells>10 was shorter in the optimal collection groups. These findings suggest that for patients with a PB CD34+ cell count below 10/µL on Day 13 following CY or 1 day after the WBC>1 × 10(9) /L, addition of plerixafor may be helpful to salvage the mobilization attempt.

Assessment of Bone Marrow Biopsy and Cytogenetic Findings in Patients with Multiple Myeloma

Objective: Multiple myeloma (MM) is a malignant condition characterized by the accumulation of malignant plasma cells. Although MM remains incurable, the survival of MM patients has improved considerably due to the application of autologous stem cell transplantation, novel agents, and advanced treatment strategies. This study aimed to determine the cytogenetic characterization and bone marrow (BM) features of Turkish patients with MM. Materials and Methods: Eighty-five MM patients were admitted to Dokuz Eylül University Hospital in Turkey. BM samples of these MM patients were subjected to cytogenetic analyses at diagnosis and during therapy as a part of therapeutical and clinical evaluation. A complete cytogenetic study was performed using the G-banding technique. Fluorescence in situ hybridization (FISH) analysis was performed using cytoplasmic immunoglobulin. The degree of BM fibrosis was determined using reticulin histochemical staining. We determined the percentage of BM plasma cells based on the extent of CD38 staining. Results: Eighty-five MM patients were retrospectively identified between 2015 and 2021. The median age was 63 (38-90) years. Of the 85 patients, 60 (70.6%) were male and 25 (29.4%) were female. Seventy-two (84.7%) cases had BM fibrosis at the time of diagnosis. The most common was grade 2 fibrosis, recorded in 35 cases (41.2%). About 72.9% of the patients showed more than 50% plasma cells. FISH analysis indicated the presence of abnormal chromosomes in 37% (32/85) of the patients. The most frequent abnormality was Immunoglobulin heavy-chain (IGH) translocation (21.3%). Conclusion: Subgroup analysis of IGH mutations is crucial in the identification of high-risk MM patients. We believe that our study will contribute to the determination of BM biopsy and cytogenetic features of MM patients in our country.

Therapeutic plasma exchange in neurological diseases: Eleven years experience at a tertiary care center in Turkey.

Therapeutic plasma exchange (TPE) is an apheresis procedure in which plasma is separated from the blood cellular components ex vivo, allocated, and replaced with another plasma or a plasma-replacing fluid. This study aimed to define the rate of complications and determine TPE distribution in various neurological diseases. Our study is a retrospective analysis of neurologic diseases requiring TPE between 2008 and 2019 that were selected using the medical records of neurology departments and apheresis units database. We performed 1459 TPE procedures on 207 patients between 2008 and 2019. TPE Procedure is most frequently applied in patients with Myasthenia-Gravis syndrome (34.7%). The complication ratio was 1.6% from a total of 1459 TPE procedures. The most commonly specified adverse event was allergic reactions 11 (5.3%), followed by hypotension 6 (2.9%). TPE was safe and tolerable, with manageable complications in experienced hands.

Adaptive phenotypic modulations lead to therapy resistance in chronic myeloid leukemia cells.

Tyrosine kinase inhibitor (TKI) resistance is a major problem in chronic myeloid leukemia (CML). We generated a TKI-resistant K562 sub-population, K562-IR, under selective imatinib-mesylate pressure. K562-IR cells are CD34-/CD38-, BCR-Abl-independent, proliferate slowly, highly adherent and form intact tumor spheroids. Loss of CD45 and other hematopoietic markers reveal these cells have diverged from their hematopoietic origin. CD34 negativity, high expression of E-cadherin and CD44; decreased levels of CD45 and ß-catenin do not fully confer with the leukemic stem cell (LSC) phenotype. Expression analyses reveal that K562-IR cells differentially express tissue/organ development and differentiation genes. Our data suggest that the observed phenotypic shift is an adaptive process rendering cells under TKI stress to become oncogene independent. Cells develop transcriptional instability in search for a gene expression framework suitable for new environmental stresses, resulting in an adaptive phenotypic shift in which some cells partially display LSC-like properties. With leukemic/cancer stem cell targeted therapies underway, the difference between treating an entity and a spectrum of dynamic cellular states will have conclusive effects on the outcome.

Prognostic Factors in Elderly Patients with Diffuse Large B-Cell Lymphoma and Their Treatment Results

Objective: Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma (NHL). The treatment of older NHL patients has always been a struggle; however, treatment statistics have begun showing favorable results similar to those of younger DLBCL patients thanks to newer treatment protocols. Here, we analyze the progress of our own elderly DLBCL patients who were followed between 2000 and 2016 in our center. Materials and Methods: Eighty-seven DLBCL patients, who were diagnosed and treated in the Dokuz Eylül University Department of Hematology between 2000 and 2016, were included in this study. Median age was 72 (65-89) years and 13 (14.9%) patients were older than 80 years. Results: Median follow-up time was 19 months and 45 patients (51.7%) died during the follow-up period. Median overall survival (OS) was 55 months and median progression-free survival was calculated as 27 months. Sixty-three patients (72.4%) received standard R-CHOP therapy. Complete response was seen in 46 (52.9%) patients. The median survival time for patients who had complete response was 136 months (p<0.001); however, OS was not statistically different between older (>80 years) and younger patients (p=0.236). Conclusion: According to our findings, we think that being able to complete standard R-CHOP therapy is vital for the survival rate of elderly DLBCL patients.

Does Reinfusion of Stem Cell Products on Multiple Days Affect Engraftment?

Objective: High-doses of melphalan treatment with autologous stem cell transplantation in multiple myeloma (MM) remains a major treatment modality in suitable patients. A minimal dose of 2x106/kg CD34+ cells is preferred to achieve engraftment. Some patients need multiple leukapheresis procedures to achieve the necessary number of CD34+ cells, but this can cause a high volume of stem cell product that cannot be given in a single day. Whether or not the number of infusion days affects engraftment has not been studied before. We aimed to evaluate the impact of reinfusion of stem cells on multiple days on engraftment results. Materials and Methods: Demographic features, CD34+ cell doses, neutrophil and platelet engraftment days, hospitalization days, and number of infusion days of 149 autologous transplantations of 143 MM patients were evaluated retrospectively. Results: The data of 143 MM patients who were transplanted were analyzed retrospectively. Median age was 55±8.5 (range: 26-70) years with a male/female ratio of 91/58. Hospitalization days for all patients were 24±6 (range: 14-50) days. Mean CD34+ cell number was (7.5±5.3)x106/kg (range: 1.5-31x106/kg). CD34+ cells were reinfused in 1 day in 80.5% (n=120) of the patients, 2 days in 18.2% of the patients (n=27), and 3 days in 1.3% of the patients (n=2). For 29 patients, reinfusion was applied in more than 1 day because of the high volume of stem cell product. We did not see any dimethyl sulfoxide toxicity, cardiac arrhythmia, or volume overload complications. Hypertensive attacks during infusion were easily controlled by furosemide treatment. In the group with multiple infusions, the infused CD34+ cell numbers had a mean of (4.8±2.8)x106/kg, and in the single infusion group the mean was (8.1±5.5)x106/kg. There were no statistical differences between the two groups regarding platelet and neutrophil engraftment days (p=0.850, r=0.820 and p=0.500, r=0.440). There was no statistical difference between the two groups for hospitalization days (p=0.060, r=0.050). Conclusion: In cases with a high volume of stem cell product to acquire adequate stem cells, reinfusion can be safely applied across multiple days without any delay in engraftment.

The effect of imatinib mesylate on the erythroid colony formation from patients with polycythemia vera in the presence of different cytokines.

It has been shown that imatinib mesylate, a drug used in the treatment of chronic myelogenous leukemia, inhibits the effect of stem cell factor, which has a central role in erythropoiesis. In some polycythemia vera (PV) patients, it has inhibited autonomous erythroid colony growth in vitro and decreased the need for phlebotomy. In this study we have investigated the effect of insulin like growth factor (IGF)-I, stem cell factor (SCF) and erythropoietin (Epo) with interleukin (IL)-3, granulocyte macrophage-colony stimulating factor (GM-CSF) and granulocyte-colony stimulating factor (G-CSF) in the presence of imatinib mesylate on the erythroid progenitors derived from peripheral blood mononuclear cells of three patients with PV and four healthy controls in semisolid medium. Erythroid colony formation from hematopoietic progenitors obtained from healthy controls was observed only in the presence of all cytokines. However, the number of erythroid colonies could not reach that of patients with PV. Inhibition of imatinib mesylate on erythroid colony growth was evident. Hematopoietic progenitors of patients with PV displayed two types of colony formation: the first type was exogenous cytokine-independent and was hypersensitive to current cytokines, and the second displayed hypersensitivity to current exogenous cytokines, but was exogenous cytokine-dependent. For both types, the inhibitory effect of imatinib mesylate was striking in the presence of all cytokines including IL-3, GM-CSF and Epo. There is no direct evidence yet that imatinib mesylate could inhibit the effect of IL-3, G-CSF, GM-CSF, Epo and IGF-I on erythropoiesis. Considering former studies together with results of this study, it can be argued that imatinib mesylate is effective in PV on the intersecting signal transduction mechanisms in which stem cell factor and its receptor may have a part.

Plasma levels of thrombin activatable fibrinolysis inhibitor antigen in active and inactive inflammatory bowel disease.

BACKGROUND: The clinical course of patients with inflammatory bowel disease (IBD) is frequently complicated by thromboembolic events and may involve the arterial and venous systems. Although not uniformly documented, several studies document substantial alterations in markers of coagulation and fibrinolysis in patients with IBD. METHODS: 45 patients with IBD (31 UC,14 CD) were included in the study. Age and sex matched 16 volunteers were used as a control group. TAFI antigen was determined using an ELISA kit VisuLiseTM for quantitative measurement. RESULTS: Inflammatory parameters such as white blood cell, platelet levels, erythrocyte sedimentation rate, C-reactive protein were found to be significantly higher in active disease group compared to inactive patients. Coagulation parameters of prothrombin time, activated partial thromboplastin time and d-dimer levels showed no significant difference between active and inactive IBD. Fibrinogen levels were significantly higher in clinically active IBD patients. Plasma TAFI levels demonstrated no significant difference between active and control, inactive and control as well as active and inactive groups. We observed no significant changes in levels of ß-TG and PF-4 between active and inactive disease group. CONCLUSIONS: We studied plasma TAFI levels in IBD. In conclusion, plasma TAFI levels does not appear to represent to be a marker of activation in IBD in contrast to literature. So further studies covering more patients with different clinic and disease activity status might improve the perspective on this issue.

Cyclo-oxygenase 2 inhibitor, nabumetone, inhibits proliferation in chronic myeloid leukemia cell lines.

The anti-tumor effect of cyclo-oxygenase (COX) inhibitors has been documented in several studies. COX2 inhibitors have attracted more attention because of the fewer side-effects and the more prominent anti-tumor effects. However, experience with these drugs in hematological malignancies is limited. In our study, a potent COX2 inhibitor, nabumetone (NBT), was investigated for its anti-proliferative and apoptotic effects in K-562 and Meg-01 chronic myeloid leukemia blastic cell lines as a single agent or in combination with adriamycin (ADR) and interferon alpha (IFN-a). In these cell lines, a dose-dependent inhibition of proliferation was observed with NBT. We observed no significant apoptotic effect of NBT. However, NBT potentiated the apoptotic effect of ADR in the K-562 cell line. Bcl-2 expression was reduced by NBT (11% vs. 2%). The combination of NBT with IFN did not have any significant effect on the K-562 cell line. We suggest that NBT inhibits proliferation and potentiates the apoptotic effect of ADR in chronic myeloid leukemia cell lines.

Bilateral primary orbital non-Hodgkin's lymphoma in a patient with scleroderma: a case report.

Orbital presentation of non-Hodgkin's Lymphoma (NHL) is uncommon but occurs both as the only site of disease and as a site of recurrence. Primary orbital NHLs are usually low-grade, and mostly extranodal marginal zone/mucosa associated lymphoid tissue B-cell neoplasms. They are commonly associated with chronic inflammatory conditions. The issue of bilaterality in orbital lymphoma is not very common. The onset of malignant lymphoproliferation may precede, follow, or exist simultaneously with scleroderma. Different treatment modalities were applied in orbital NHL such as surgery, radiation therapy, chemotherapy or both. We report a 57-year-old man with scleroderma presenting with eyelid hernias who had biopsy-proven marginal zone NHL, successfully treated with radiotherapy and combined chemotherapy, and also review the literature.

Renal and neurological response with eculizumab in a patient with transplant associated thrombotic microangiopathy after allogeneic hematopoietic progenitor cell transplantation.

Transplantation-associated thrombotic microangiopathy (TA-TMA) is a challenge after allogeneic hematopoietic progenitor cell transplantation, considering the diagnostic uncertainties and lack of established treatment. We report a 43-year-old male patient who was diagnosed as TA-TMA after allogeneic progenitor cell transplantation for a progressive ALK negative anaplastic large cell lymphoma and responded to eculizumab with dramatically improving neurological status and renal function. Rapid neurological and renal recovery achieved after eculizumab could support a possible relationship between complement activation and TA-TMA. Eculizumab should be a reasonable treatment approach in patients with TA-TMA after allogeneic hematopoietic progenitor cell transplantation.

Nilotinib Does Not Alter the Secretory Functions of Carotid Artery Endothelial Cells in a Prothrombotic or Antithrombotic Fashion.

BACKGROUND: There have been concerns about the possible prothrombotic effects of nilotinib, especially in patients having cardiovascular risk factors. The potential mechanism behind the increased risk of thromboembolic events is still not clear. OBJECTIVES: In this study, we aimed to evaluate possible harmful effects of nilotinib on endothelial cells. To this aim, we examined proliferative capacity and secretory functions of healthy human carotid artery endothelial cells (HCtAECs) in response to nilotinib. METHODS: 3-(4,5-Dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) cell proliferation method was used to determine antiproliferative effects of nilotinib on HCtAECs. The HCtAECs were incubated with 5, 10, and 100 nmol/L doses of nilotinib for 72 hours. Then, in order to assess the endothelial function, levels of nitric oxide (NO), von Willebrand factor (vWF), tissue plasminogen activator, plasminogen activator inhibitor 1 (PAI-1), and endothelin 1 (ET-1) were evaluated using enzyme-linked immunosorbent assay from tissue culture supernatants. RESULTS: There were slight but statistically significant decreases in cell proliferation in response to nilotinib. Nilotinib increased the secretion of t-PA, PAI-1, and vWF in a dose-dependent manner when compared with the untreated control group. The ET-1 secretion was lower in 5 nmol/L and higher in 10 and 100 nmol/L nilotinib-treated cells as compared to untreated cells. Regarding NO secretion, lower levels were observed in 5 and 10 nmol/L, and higher levels were detected in 100 nmol/L nilotinib-treated cells as compared to untreated control group cells. CONCLUSION: Considering the results obtained in our study, nilotinib does not affect the functions of endothelial cells either in a prothrombotic or an antithrombotic fashion, despite a dose-dependent decline in cell viability.

IPSET-Thrombosis Better Identifies Thrombosis-Free Survival: A Turkish Cohort.

INTRODUCTION: Essential thrombocythemia (ET) is the most common of the myeloproliferative neoplasms. For better predicting the occurrence of thrombotic events, an International Prognostic Score of Thrombosis for ET (IPSET-Thrombosis) was recently developed. We aimed to investigate the validity of IPSET-Thrombosis in a Turkish patient cohort and to compare the efficacy of IPSET-Thrombosis and conventional risk scoring systems in predicting thrombosis-free survival. PATIENTS AND METHODS: We retrospectively evaluated the clinical characteristics and risk factors for thrombosis in 112 Turkish patients. Median thrombosis-free survival and Harrell C concordance indexes were calculated for both conventional and IPSET-Thrombosis. RESULTS: Median age of 112 patients included in the study was 61 (range, 27-90) years at the time of diagnosis. When patients were stratified according to the conventional risk stratification system, 43.8% of patients were in the low-risk group and 56.2% in the high-risk group. A total of 22.4% of low-risk and 42.9% of high-risk patients had at least one thromboembolic event. When patients were stratified according to the IPSET-Thrombosis, 33% were in the low-risk group, 26.8% in the intermediate-risk group, and 40.2% in the high-risk group. Considering IPSET-Thrombosis risk groups, 5.4% of low-risk, 26.7% of intermediate-risk, and 66.2% of high-risk patients had at least one thromboembolic event. Regarding IPSET-Thrombosis risk groups, 10-year thrombosis-free survival was 86.8% for low-risk, 39.4% for intermediate-risk, and 32.9% for high-risk groups (P < .001). Harrell C concordance indexes of conventional and IPSET-Thrombosis were 0.60 and 0.77, respectively. CONCLUSION: By validating the reproducibility of IPSET-Thrombosis in Turkish ET patients, we found that IPSET-Thrombosis identifies thrombosis-free survival better than the conventional risk stratification system.