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Aim: To determine the unmet needs and challenges in management, diagnosis, treatment, follow-up and patient-physician communication in acute leukemia (AL). Materials & methods: The study was based on a modified Delphi approach. A questionnaire including the major potential obstacles was circulated twice among 13 hematologists. Results: The obstacles in AL management were limited access to the novel treatments and genetic tests, limited bed capacity, insufficient level of knowledge among allied health personnel, limited availability of psycho-oncological support and low levels of awareness in the population about the importance of stem cell donation. Conclusion: The challenges in the management of AL are critical to guide the efforts to improve the quality of healthcare delivery and the evidence-based decision making at treatment of AL patients.

Tyrosine kinase inhibitors (TKIs) approved for chronic myeloid leukemia known to have similar efficacies but different safety profiles. Therefore, the choice of patient-specific treatments is driven by factors such as tolerability and adverse event profile of TKIs. This review article examines the most up-to-date data and provides practical recommendations for clinical approaches. Nilotinib and ponatinib should be avoided in patients with cardiovascular risk factors, dasatinib in patients with lung damage and bosutinib and nilotinib in patients with liver disease. Considering that certain comorbidities predispose some patients to developing severe adverse events when receiving TKIs, the first- and second-line treatment of chronic myeloid leukemia should be tailored to each patient's individual condition., Competing Interests: Financial & competing interests disclosure All authors received an honorarium from Pfizer in connection with the development of this study. G Saydam has acted in advisory board of Novartis, AbbVie, Amgen, Pfizer Pharmaceuticals and Bristol Myers Squibb and has received speaker honorarium from Novartis. R Ali has acted in advisory board of Novartis, Amgen, Pfizer Pharmaceuticals and Bristol Myers Squibb and has received speaker honorarium from Novartis, Amgen and Pfizer Pharmaceuticals. AM Demir has acted in advisory board of Novartis, AbbVie, Amgen, Pfizer Pharmaceuticals and Bristol Myers Squibb and has received speaker honorarium from Novartis. AE Eskazan has acted in advisory board of Novartis and Pfizer Pharmaceuticals, and has received speaker honorarium from Pfizer Pharmaceuticals, Bristol Myers Squibb and Novartis. B Guvenc has acted in advisory board of Novartis, AbbVie, Amgen, Pfizer Pharmaceuticals and Bristol Myers Squibb and has received speaker honorarium from Novartis. IC Haznedaroglu has acted in advisory board of Novartis, Pfizer Pharmaceuticals and Bristol Myers Squibb and has received speaker honorarium from Novartis. MA Ozcan has acted in advisory board of Novartis, AbbVie, Amgen, Pfizer Pharmaceuticals, and Bristol Myers Squibb and has received speaker honorarium from Novartis. O Salim has acted in advisory board of Novartis, AbbVie, Amgen, Pfizer Pharmaceuticals and Bristol Myers Squibb. M Sonmez has acted in advisory board of Novartis, AbbVie, Amgen, Pfizer Pharmaceuticals and Takeda and has received speaker honorarium from Novartis. M Turgut has acted in advisory board of Novartis, Pfizer Pharmaceuticals, and Bristol Myers Squibb and has received speaker honorarium from Novartis. ATT has acted in advisory board of Novartis, AbbVie, Pfizer Pharmaceuticals, and Takeda and has received speaker honorarium from these companies. A Unal has acted in advisory board of Novartis, AbbVie, Amgen, and Bristol Myers Squibb and has received speaker honorarium from Novartis. S Bozkurt, B Aver and B Ozdengulsun are employees in Pfizer Pharmaceuticals. O İlhan has acted in advisory board of Novartis, AbbVie, Amgen, Pfizer Pharmaceuticals, Bristol Myers Squibb, Janssen Pharmaceutical, Deva Holding, Nobel Ilac and Roche. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Medical Writing support was provided by Ayşe Özlem Yılmaz and submission assistance was provided by İlknur Kehlibar at Remedium Consulting Group and was funded by Pfizer., (© 2022 Guray Saydam and all co-authors.)

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., Competing Interests: None., (AJBR Copyright © 2021.)

Peripheral blood is the prefered source for hematopoietic stem cells for hematopoietic stem cell transplantation. The efficiency of peripheral blood stem cell (PBSC) collection can vary among devices. In this study we aimed to compare feasibility and effectivity of apheresis procedures of the different systems. Two apheresis systems [Com.Tec (Fresenius Healthcare) and Spectra Optia (Caridian BCT)] were used in our center for the collection of PBSCs for autologous and allogeneic transplantation. We retrospectively analysed 190 apheresis procedures performed in healthy donors and patients between June 2012 and November 2014 in Department of Hematology, Dokuz Eylul University. PBSCS were collected by Fresenius cell separator (64 procedure) or Spectra Optia cell separator (126 procedure). Mobilization treatments were G-CSF (26.8%), cyclophosphamide plus G-CSF (48.4%), prelixafor plus G-CSF (14.7%), ESHAP (10%) and others. Patient and donor characteristics (age, weight, volume processed, disease, mobilization regimes) were similar in Fresenius and Spectra Optia apheresis groups. Altough both collected PBSCs efficiently, the amount of CD34+ cell in product collected by Spectra Optia device was significantly higher ( p  < 0.05) and product volume was lower than Fresenius Com.Tec significantly ( p  < 0.05). "CD34+ collection efficiency" with Spectra Optia was significantly higher than Fresenius Com.Tec (CE2: 87%, 70%, p  = 0.033) regarding all procedures. High collection efficiency and low product volume may be a significant characteristic of Spectra Optia device (mean 187 mL, product CD34+ cell: 1576 µL)., Competing Interests: Compliance with Ethical StandardsThe author did not receive financial compensation for authoring the manuscript.

Background: Recent reports showed neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR), as a predictor of progression-free survival (PFS) and overall survival (OS) in various malignancies., Materials and Methods: We retrospectively examined the PLR, NLR, and MLR in a cohort of 186 newly diagnosed multiple myeloma (MM) patients. This study investigated the prognostic relevance of NLR, PLR, and MLR in MM patients. NLR, PLR, and MLR were calculated from whole blood counts before therapy. The Kaplan-Meier curves and multivariate Cox models were used for the evaluation of survival., Results: Applying cutoff of 1.9 (NLR), 120.00 (PLR), and 0.27 (MLR), decreased PLR showed a negative impact on the outcome. Decreased PLR is an independent predictor for PFS and OS. There were no significant differences in median survival between the high and low NLR ( P = 0.80) and MLR ( P = 0.87) groups., Conclusions: In this study, thrombocytopenia and low PLR are associated with poor survival in MM patients does this P value apply to thrombocytopenia or low PLR and may serve as the cost-effective prognostic biomarker., Competing Interests: There are no conflicts of interest.

We describe a 36-year-old woman with a relapsing Hodgkin's lymphoma who developed a severe bilateral sudden visual loss almost three weeks after the initiation of brentuximab therapy. Ancillary fundus tests yielded bilateral severe retinal arteriolar occlusion 360° and serous macular retinal detachment. No visual improvement could be achieved despite the pulse corticosteroid therapy and a single bilateral intravitreal aflibercept administration cessation of the brentuximab therapy. Unfortunately, she succumbed to respiratory failure almost six weeks after the diagnosis of Purtscher-like retinopathy., Competing Interests: The authors declare that they have no competing interests.

PNH Education and Study Group (PESG) have been established in December 2013 as a non-profit, independent, medical organization www.pesg.org. Paroxysmal Nocturnal Hemoglobinuria (PNH) is a multi-systemic disease that should be treated with a multidisciplinary approach. Patients may apply to the clinics other than the hematology due to variability and diversity of clinical findings which lower the rate of diagnosis due to low awareness about PNH. PNH might be overlooked and diagnosis might be delayed. Regarding these, PESG was established with the collaboration of Immunology, Cardiology, Thorax Diseases (Pulmonology), Neurology, Gastroenterology, General Surgery and Urology specialists in addition to hematologists dealing with PNH. The PESG study group aims to increase the awareness about PNH, including training activities about PNH, strengthening the relations between clinics and planning of clinical studies as a goal. It is the first professional organization focusing on PNH, in Turkey.In this guideline, we want to facilitate the diagnosis attributes of physicians from all specializations that deal with PNH and its systemic complications. One can perceive this as a tailor made guideline of international guidelines but not a compilation.

Multiple myeloma (MM) is a hematologic cancer characterized by malignant proliferation of plasma cells and their precursors. Immunosuppressive CD4+CD25+Foxp3+ regulatory T (Treg) cells are increased in the peripheral blood of patients with MM. On the basis of this finding, we sought to evaluate the ex vivo effect of CD4+CD25+Foxp3+ Treg cells on the anti-tumor effect of the proteosome inhibitor bortezomib on MM cells. We collected peripheral blood and bone marrow aspiration samples from 20 patients with newly diagnosed MM and isolated CD4+CD25+Foxp3+ Treg cells from peripheral blood mononuclear cells. The bone marrow mononuclear cells were cultivated in RPMI at 37°C and 5% CO2 for 72 hours. The LD50 doses of bortezomib, isolated Treg cells, and their combination were added. After 24 hours, the viability of CD138+ myeloma cells was evaluated by WST-1. We compared the anti-tumor effect of bortezomib alone and in combination with Treg expansion and statistically analyzed the measured differences with respect to the clinical parameters of the patients. Treg cells had varied effects on bortezomib, increasing, decreasing, or not changing its anti-tumor effect. The increased in vitro anti-tumor effect of bortezomib after Treg cell expansion was correlated in patients who did not develop bortezomib resistance in vivo (p = 0.022). These patients with in vivo non-bortezomib-resistant MM also responded to Treg expansion with decreased cell viability (p = 0.024). Our data indicate that the ex vivo expansion of Treg cells increased the cytotoxic effect of bortezomib in clinically sensitive cases., (Copyright © 2016 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.)

Purpose: Women with previous gestational diabetes mellitus (pGDM) are at high risk for type 2 diabetes and cardiovascular disorders. In this study, we aimed to compare plasma apelin levels between women with and without pGDM, and to investigate the possible association of apelin with cardiometabolic risk factors., Methods: Among 252 consecutive Caucasian women with GDM being included in a prospective postpartum follow-up protocol, 141 women eligible for the study protocol were enrolled. Control group consisted of 49 age- and body mass index-matched healthy women without pGDM. Circulating apelin, IL-6 and plasminogen activator inhibitor levels, and carotid intima media thickness (IMT) were measured. To evaluate carbohydrate intolerance, 75-g oral glucose tolerance test was performed. Fasting insulin and lipids were measured, and homeostasis model assessment index was calculated., Results: Plasma apelin levels were reduced in women with pGDM (p < 0.001). In multiple regression analysis, apelin was negatively associated with fasting (r (2) 0.090, β -0.273, p = 0.001) and post-load glucose (r (2) 0.061, β -0.187, p = 0.022), serum IL-6 (r (2) 0.082, β -0.234, p = 0.002), and carotid IMT (r (2) 0.057, β -0.168, p = 0.033)., Conclusions: Our results suggested that suppressed apelin levels were associated with increased cardiovascular risk in women with pGDM.

Objective: Women with gestational diabetes mellitus (GDM) treated with insulin are more likely to develop type 2 diabetes after pregnancy compared to mild GDM cases treated with medical nutrition treatment (MNT) alone. We aimed to compare levels of subclinical atherosclerosis markers in women with previous GDM treated with insulin and MNT alone., Methods: Eighty-one women with previous GDM (45 treated with insulin, 36 treated with MNT) and 35 age-matched lean controls were included. Fasting glucose, insulin and lipids, circulating fibrinogen, CRP, PAI-1 and IL-6 levels were assayed. Carotid intima media thickness (IMT) was measured., Results: Women with previous GDM treated with insulin in pregnancy had significantly higher fasting glucose, plasma PAI-1 levels and carotid IMT compared to women treated with MNT alone. In multiple regression analysis, insulin need in pregnancy was associated with increased carotid IMT and plasma PAI-1 levels (corrected for age, BMI, postpartum duration, fasting glucose and lipids; model r(2)=0.132; beta=0.297, p=0.014 for carotid IMT; model r(2)=0.198; beta=0.345, p=0.003 for PAI-1)., Conclusion: Women with previous GDM treated with insulin in pregnancy had a worse cardiovascular risk profile compared to mild GDM patients. An intensive preventive approach for cardiovascular disorders is particularly essential for this subgroup of women.

Objective: The aim of this prospective study was to investigate the effect of LT4 suppression therapy on plasma thrombin activatable fibrinolysis inhibitor (TAFI) antigen and plasminogen activator inhibitor-1 (PAI-1) levels in benign thyroid nodules. We also compared hyperthyroid patients and healthy controls., Subjects and Methods: Twenty premenopausal women with benign thyroid nodules were given LT4 suppression therapy for 1 year. Plasma TAFI and PAI-1 antigen levels were measured at baseline and after LT4 suppression treatment. The endogenous hyperthyroid group was composed of 19 premenopausal females with newly diagnosed endogenous hyperthyroidism. Eighteen age-matched euthyroid healthy premenopausal women were enrolled as the control group., Results: TAFI antigen levels decreased after LT4 suppression treatment; however, the difference was not statistically significant (p = 0.057). LT4 treatment resulted in a nonsignificant increase in PAI-1 levels. Patients with endogenous hyperthyroidism had decreased levels of TAFI antigen and increased levels of PAI-1 antigen (p < 0.05). There was a negative correlation between the FT(4) and TAFI antigen levels. Serum TSH was positively correlated with the plasma levels of TAFI antigen., Conclusion: LT4 suppression therapy for benign thyroid nodules did not result in a significant decrease in TAFI antigen levels in premenopausal women, but endogenous hyperthyroidism was associated with significantly decreased levels of TAFI antigen., (Copyright © 2010 S. Karger AG, Basel.)

A patient with mantle cell non-Hodgkin's lymphoma presented herself with fever, nausea, right upper quadrant pain on the 7th day of R-CHOP chemotherapy. After hospitalization with the suspicion of acute cholecystitis, she received antibiotherapy with G-CSF because of emerging neutropenia at the 10th day of chemotherapy. Abdominal computed tomography revealed small infarcts in the spleen and kidneys. The ecchymotic lesion which developed on her right lateral malleolus, became bullous in the following days and treated as ecthyma gangrenosum. Although the patient was afebrile with a normal neutrophil count on the third day of antibiotherapy, she developed acute renal failure and deteriorated rapidly. The patient underwent hemodialysis but expired on the 10th day of hospitalization. Post mortem autopsy findings showed ischemic infarction and necrosis of parenchyma due to mycotic thrombosis of arteries and veins of many organs (heart, lung, diaphragm, kidneys, spleen, gut mucosa) as well as invasion of vessel walls and parenchyma by mucor. We reviewed mucormycosis in the light of this case.

Non Hodgkin's lymphomas (NHL) of the thyroid are rare thyroid neoplasms. The majority of histopathologic types are extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type and, diffuse large B-cell lymphoma (DLBCL). Most of them arise in a background of Hashimoto's thyroiditis and patients mostly present with a rapidly enlarging thyroid mass and with pressure symptoms. Treatment depends on the histological subtype and stage of the disease and includes radiotherapy and chemotherapy. The prognosis usually is favorable with proper treatment. Herein, we discuss the clinical diagnosis and treatment of thyroid lymphoma.

AA-type amyloidosis is a consequence of a long-standing systemic inflammation and is not associated with a monoclonal protein or clonal bone marrow plasma cells. Proinflammatory cytokines such as interleukin (IL)1, IL-6, and tumor necrosis factor (TNF) stimulate the synthesis of serum amyloid A during inflammation. Although the association of non-Hodgkin's lymphoma (NHL) with AL-type amyloidosis is well known and patients with Hodgkin's lymphoma with AA amyloidosis have been described, AA-type amyloidosis with NHL is extremely infrequent. We report a case of amyloidosis associated with NHL that subsided during R-CHOP chemotherapy.

Background and Aims: In this study, we investigated whether reticulated platelets (RP) would be useful markers in the evaluation of ulcerative colitis (UC) activity and also aimed to gain indirect information about the platelet kinetics., Materials and Methods: Complete blood count, C-reactive protein, erythrocyte sedimentation rate, and proportion of RP were measured in 16 active, 21 inactive UC patients, and 20 healthy blood donors. UC activity was assessed by Truelove-Witts criteria., Results: Mean platelet count was increased in patients with active compared to inactive UC (p=0.008) or healthy donors (p=0.000). Mean platelet volume (MPV) was significantly decreased in patients with active compared to inactive (p=0.015) and healthy donors (p=0.001). RP values was significantly decreased in active and inactive UC groups compared to healthy donors (p=0.000, p=0.000, respectively), while there was no significant difference between active and inactive UC patients (p=0.980). Significant negative correlation between platelet count and MPV in patients with active UC (r=-0.542, p=0.030) was observed., Conclusions: RP values is reduced in active and inactive UC patients compared to healthy donors. To our knowledge, this is the first study about proportion of RP with UC in literature. However, the role of low RP values have not been determined clinically. Further studies are needed to evaluate the role of platelet abnormalities and changes in megakaryopoiesis caused by inflammatory state on low MPV and RP values during the course of UC.

Both increased and decreased fibrinolytic activity have been reported in patients with hyperthyroidism. Elevated levels of plasma plasminogen activator inhibitor-1 (PAI-1) antigen have been found in hyperthyroid patients. Thrombin activatable fibrinolysis inhibitor (TAFI) is a novel plasma protein, which inhibits fibrinolysis through removal of C-terminal lysines from partially degraded fibrin. Previously, we showed that plasma TAFI antigen levels were increased in patients with overt and subclinical hypothyroidism. The aim of this study is to investigate plasma levels of TAFI and PAI-1 antigens in hyperthyroid patients. PAI-1 and TAFI antigen levels were measured in the plasma of 29 patients with hyperthyroidism (14 overt hyperthyroid and 15 subclinical hyperthyroid), and 26 healthy individuals. Although there were increased levels of PAI-1 antigen in hyperthyroid patients, plasma TAFI antigen levels were significantly lower compared to controls (80.79 ng/ml vs. 32.42 ng/ml, p = 0.000 for PAI-1; 10.42 microg/ml vs. 12.24 microg/ml, p = 0.009 for TAFI). Elevated PAI-1 antigen levels were positively correlated with free thyroid hormones, although TAFI antigen levels were in negative correlation with free thyroxine. Furthermore, an inverse correlation between PAI-1 and TAFI antigen levels was found. Our study demonstrated that TAFI antigen levels were decreased in patients with hyperthyroidism. Inverse correlation with PAI-1 suggests that the decrease in TAFI antigen levels may be due to activation of TAFI pathway. Further studies evaluating the underlying mechanisms of low TAFI antigen levels in hyperthyroidism should be undertaken.

Introduction: Bisphosphonates are mostly used in the treatment of bone metastases. They have been shown to act synergistically with other chemotherapeutic agents. It is not known, however, whether similar synergistic effects exist with radiation on breast cancer cells., Methods: Human MCF-7 breast cancer cells were treated with up to 100 microM zoledronic acid, were irradiated with up to 800 cGy or were exposed to combinations of both treatments to determine the antiproliferative effects of zoledronic acid and radiation., Results: Zoledronic acid and radiation caused a dose-dependent and time-dependent decrease in cell viability (approximate 50% growth inhibition values were 48 microM and 20 microM for 24 hours and 72 hours, respectively, for zoledronic acid and 500 cGy for radiation). A synergistic cytotoxic effect of the combination of zoledronic acid and radiation was confirmed by isobologram analysis., Conclusion: These data constitute the first in vitro evidence for synergistic effects between zoledronic acid and radiation. This combination therapy might thus be expected to be more effective than either treatment alone in patients with metastatic breast carcinoma.