Omur Gokmen Sevindik

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.

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.

A Rare Cause of Renovascular Hypertension: Takayasu Arteritis with Only Renal Artery Involvement

Takayasu arteritis is a chronic inflammatory disease that affects mainly the aorta, main branches of aorta, and pulmonary arteries with unknown etiology. Disease affecting solely the renal arteries is rare. We will present a case that had hypertension, hypokalemia, and metabolic alkalosis where the etiology was type 2 Takayasu arteritis, affecting renal arteries.

Hypoalbuminemia is a surrogate biomarker of poor prognosis in myelodysplastic syndrome even when adjusting for comorbidities.

The serum albumin (SA) level has been reported to be an independent prognostic biomarker that may serve as a surrogate representative of disease biology in patients diagnosed with myelodysplastic syndrome (MDS). However, its prognostic ability has not been tested in a model adjusting for comorbidities. We analyzed 200 patients who were diagnosed as having de novo MDS. Median overall survival (OS) of all patients was 25 months and median leukemia-free survival (LFS) was 24 months. Median OS according to the SA level groups of ≤ 3.5, 3.6–4.0 and > 4.0 mg/dL were 24, 39 and 77 months, respectively. SA level remained an independent predictor of both LFS and OS even when adjusting for the hematopoietic cell transplant comorbidity index (HCT-CI) and the International Prognostic Scoring System (IPSS) or World Health Organization classification-based Prognostic Scoring System (WPSS). Our findings indicate that SA level at the time of diagnosis is a significant and independent predictor of LFS and OS even when adjusting for commonly used prognostic systems and comorbidities.

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.

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.

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?

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.

Successful hematopoietic engraftment with gray platelets after allogeneic hematopoietic stem cell transplantation from gray platelet syndrome donor.

Gray platelet syndrome (GPS) is a rare inherited disorder characterized by the absence of &agr;-granules and their constituents. It may be present with thrombocytopenia and bleeding tendency. Platelets have a large and gray appearance under light and electron microscope. A 19-year old female patient with her second relapse acute lymphoblastic leukemia had to be consolidated with allo-hematopoietic stem cell transplantation (HSCT) after achieving remission with induction chemotherapy. The only available and one mismatch compatible donor was her brother, who was previously diagnosed as GPS. Allogeneic HSCT was performed from her brother in spite of GPS, and successful neutrophil and platelet engraftment achieved at the 12th and 42nd day of reinfusion, consecutively. The engrafted and circulating thrombocytes were large and gray and had little or no &agr;-granules under electron microscope. The patient was well with no major bleeding event and increased need for thrombocyte replacement until developing bronchiolitis obliterans organizing pneumonia and respiratory distress syndrome. Thereafter death occurred. This is the first case of successful thrombocyte engraftment with documented gray thrombocyte megakaryopoiesis after allogeneic HSCT from a GPS donor. The only noteworthy issue was the slight prolongation of engraftment.