Real-world data on the effectiveness and safety of Ixazomib-Lenalidomide-Dexamethasone therapy in relapsed/refractory multiple myeloma patients: a multicenter experience in Turkey.

A multicenter, retrospective, observational study was conducted to explore effectiveness and safety of ixazomib plus lenalidomide with dexamethasone (IRd) in relapsed/refractory multiple myeloma (RRMM) patients following at least ≥ two lines of therapy. Patients' treatment responses, overall response rate, progression-free survival rate, and adverse events were recorded. Mean age of 54 patients was 66.5 ± 9.1 years. There were 20 patients (37.0%) with progression. Median progression-free survival was 13 months in patients who received a median of three therapy lines in a 7.5-month follow-up period. Overall response rate was 38.5%. Of 54 patients, 19 (40.4%) had at least one adverse event, and nine (19.1%) had an adverse event of at least grade 3 or more. Of 72 adverse events observed in 47 patients, 68% were grade 1 or 2. Treatment was not stopped in any patient due to adverse events. IRd combination therapy was effective and safe in heavily treated RRMM patients.

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

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

Oscillometric evaluation of the effects of cardiotoxic chemotherapeutic agents on vascular stiffness.

AIM: Several clinical studies have demonstrated that arterial stiffness is an early indicator of cardiovascular events. Our study aimed to detect the potential cardiovascular changes using arterial stiffness parameters and compare these changes with echocardiographic aortic stiffness parameters, in cancer patients treated with cardiotoxic chemotherapeutics. METHODS AND RESULTS: Our study is a prospective case-control study. A total of seventy subjects between the ages of 18 and 50 years were included into our study. Thirty of them were newly diagnosed cancer patients and forty constituted the age- and sex-matched control group. Baseline oscillometric arterial and echocardiographic aortic stiffness parameters were measured in all patients. In cancer patients, all of these parameters were measured again, 1 month after chemotherapy protocol was completed. Mean age of the cancer patients was 41.4 ± 5.9 years and mean age of the control group was 39.6 ± 6.6 years (P = 0.258). Before chemotherapy, arterial and aortic stiffness parameters were similar between the study and the control group. After chemotherapy, the oscillometric pulse wave velocity parameter increased compared with the control group and to the prechemotherapy values (P = 0.004 and P < 0.001, respectively). After chemotherapy, the augmentation index parameter increased compared with the control group (P = 0.013). On the other hand, no difference was detected between the groups in terms of echocardiographic aortic stiffness parameters. CONCLUSION: In newly diagnosed cancer patients treated with cardiotoxic chemotherapeutics, considerable impairment occurs in some of the oscillometric arterial stiffness parameters, while there is no substantial effect on echocardiographic aortic stiffness. Arterial stiffness parameters in these patients might be useful in evaluating subclinical cardiovascular damage.

Efficacy of preoperative therapeutic plasma exchange in patients with hyperthyroidism and factors affecting the number of sessions.

PURPOSE: Achieving preoperative euthyroidism in patients with hyperthyroidism for whom antithyroid drugs (ATDs) cannot be used for treatment is a serious clinical problem. We aimed to evaluate the effectiveness of therapeutic plasma exchange (TPE) in hyperthyroid patients scheduled for surgery and predictive factors for a high number of TPE sessions. METHODS: We retrospectively analyzed the data of 21 patients with hyperthyroidism who were treated with TPE for preoperative euthyroidism in our institution. Pre- and post-TPE thyroid function tests were compared to assess efficacy. Binary logistic regression analysis was applied to determine predictors of patients requiring a high number of TPE sessions. RESULTS: All patients (20 patients with Graves' disease and 1 patient with toxic multinodular goiter; 12 women and 9 men; mean age 35.71 ± 12.38 years) had severe hyperthyroidism before TPE. The changes before and after TPE in fT3, fT4, and TSH levels were statistically significant (p < 0.001, p < 0.001, p = 0.002, respectively). The median number of TPE sessions was 8 (range: 1-24). Levels of fT3 before TPE were significantly higher in patients for whom higher numbers of TPE sessions were required (≥8) (OR: 1.427, 95% CI: 1.038-1.961, p = 0.028). Receiver operating characteristic curve analysis revealed an optimum cut-off value of 12.8 pg/ml for fT3 before TPE (91% sensitivity, 80% specificity, area under the curve: 0.927). CONCLUSION: TPE should be considered as an effective alternative treatment option that can be used to rapidly achieve euthyroidism before surgery when ATDs cannot be used. Pre-TPE fT3 levels of >12.8 pg/ml may be an independent factor predicting the need for higher numbers of TPE sessions (≥8).

The Real-World Experience With Single Agent Ibrutinib in Relapsed/Refractory CLL.

INTRODUCTION/BACKGROUND: The emergence of novel agents targeting the B-cell receptor pathway and BCL-2 has significantly changed the therapeutic landscape of CLL. We evaluated the safety and efficacy of single-agent ibrutinib in relapsed/refractory CLL in real-world settings. PATIENTS/METHODS: A total of 200 relapsed/refractory CLL patients with a median age of 68 were included in this retrospective, multicenter, non-interventional study. Data of the study were captured from the patient charts of the participating centers. RESULTS: The median for lines of previous chemotherapy was 2 (1-6); 62 (31.8%) patients had del17p and/or p53 mutations (del17p+/p53mut). Of the study group, 146 (75%) patients achieved at least PR, while 16 (8.7%) patients discontinued ibrutinib due to TEA. The most common drug-related adverse events were neutropenia (n: 31; 17.4%) and thrombocytopenia (n: 40; 22.3%), which were ≥ grade 3 in 9 (5%) and 5 (3.9%) patients, respectively. Pneumonia (n: 42; 23.7%) was the most common nonhematologic TEA. Atrial fibrillation (n: 5; 2.8%) and bleeding (n: 11; 6.3%) were relatively rare during the study period. Within a median follow-up period of 17 (1-74) months, 42 (21%) patients died. The estimated median OS of the study cohort was 52 months. Only the response to ibrutinib (CR/PR vs. SD/PD) was significantly associated with OS. CONCLUSION: Our results indicate good safety and efficacy for single-agent ibrutinib in R/R CLL in daily practice.

Apheresis in patients with sepsis: A multicenter retrospective study.

BACKGROUND AND OBJECTIVES: To consider the effectiveness of apheresis, which is a supportive treatment method, in sepsis. MATERIALS AND METHODS: A hundred and eleven adults with sepsis or septic shock were included in this retrospective study. The demographic characteristics of the patients, the focus and source of infection causing sepsis or septic shock, characteristics of the pathogen, Acute Physiological and Chronic Health Assessment (APACHE) II score, routine laboratory values, which apheresis method was used, the characteristics of the replacement fluids used during the apheresis procedure, the number of apheresis procedures, complications related to the apheresis procedure, the follow-up time after the procedure, and mortality were recorded. The primary outcome was 28-day mortality. RESULTS: Sixty-nine (62.2 %) of the patients were male. The mean age of the patients was 47.7 ± 18.6 years. The most common source of sepsis was hospital-acquired (79.3 %), the most common pathogen causing sepsis was gram-negative bacteria (41.4 %), and the most common infection site was the respiratory tract (58.7 %). The median APACHE II score was 19 (13-24). 92 (82.9 %) of the patients had septic shock. Theropeutic plasma exchange (TPE) was performed in 11.7 % of the patients and immunoabsorbtion IA in 88.3 %. The median number of sessions was 3 (3-5). No procedure-related fatal complication was observed in the study. While 28-day mortality was 61.3 % in all patients, when the mortality according to the apheresis procedures was examined, it was 11.3 % and 88.2 % in the patients who underwent TPE and IA, respectively. The most common cause of mortality was multiorgan failure. CONCLUSIONS: Apheresis in sepsis can be considered as a salvage treatment. The indication for apheresis in sepsis is still at the level of patient-based individualized decision in line with the studies done so far, including our study. However, there is a need for a multicenter randomized controlled study with a large number of patients in order to give positive or negative recommendations about its effectiveness.

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.

Impact of Fluorescent In Situ Hybridization Aberrations and CLLU1 Expression on the Prognosis of Chronic Lymphocytic Leukemia: Presentation of 156 Patients from Turkey.

OBJECTIVE: This study evaluates the impact of CLLU1 expression and fluorescent in situ hybridization (FISH) analysis of a group of Turkish chronic lymphocytic leukemia (CLL) patients. MATERIALS AND METHODS: A total of 156 CLL patients were analyzed by FISH method; 47 of them were also evaluated for CLLU1 expression. Results were correlated with clinical parameters. RESULTS: FISH aberrations were found in 62% of patients. These aberrations were del13q14 (67%), trisomy 12 (27%), del11q22 (19%), del17p (8%), and 14q32 rearrangements (20%). Overall del11q22 and del17p were associated with the highest mortality rates, shortest overall survival (OS), and highest need for medication. Homozygous del13q14, 14q32 rearrangements, and higher CLLU1 expression correlated with shorter OS. CONCLUSION: Cytogenetics/FISH analysis is still indicated for routine evaluation of CLL. Special consideration is needed for the poor prognostic implications of del11q22, del17p, 14q32 rearrangements, and homozygous del13q14. The impact of CLLU1 expression is not yet clear and it requires more data before becoming routine in genetic testing in CLL patients.

The relationship of T helper-2 pathway components interleukin-4, interleukin-10, immunoglobulin e, and eosinophils with prognostic markers in non-hodgkin lymphoma: a case-control study.

OBJECTIVE: Increased risk for non-Hodgkin lymphoma (NHL) is associated with infections and environmental agents. We hypothesized that these factors chronically trigger the T helper-2 (Th2) pathway and result in lymphoma. We investigated the role of the Th2 pathway by exploring the relationships between components of the Th2 pathway, interleukin (IL)-10, IL-4, immunoglobulin E (IgE), and eosinophils, and prognostic markers of NHL. MATERIALS AND METHODS: Thirty-one NHL patients and 27 healthy controls were enrolled. IL-10, IL-4, IgE, and eosinophils were measured. IL-4 and IL-10 were analyzed with the enzyme amplified sensitivity immunoassay method. RESULTS: High IL-10 levels were correlated with several poor prognostic features, short early survival, and lymphopenia. There was a positive correlation between albumin and IL-4 levels and a negative correlation between IL-10 and albumin. There was no relationship related with eosinophils and IgE. We found remnant increased IL-4, which could be a clue for the triggering of the Th2 pathway in the background. CONCLUSION: There is a need for differently designed studies to detect the place of the Th2 pathway in NHL.

Predicting survival for multiple myeloma patients using baseline neutrophil/lymphocyte ratio.

The neutrophil/lymphocyte ratio (NLR) at diagnosis has been shown to be a prognostic factor for survival in solid tumors. The NLR at diagnosis as a prognostic factor for multiple myeloma (MM) has not been studied. Therefore, the focus of the study was the correlation of NLR with the proven prognostic parameters in patients with MM. A total of 151 MM patients who fulfilled the International Myeloma Working Group (IMWG) criteria were enrolled in the study by a retrospective review of the patients' records. One hundred fifty-one age- and gender-matched healthy controls were also included in the study. NLR was calculated using data obtained from the complete blood count (CBC). NLR was significantly higher in MM patients than the control group (2.79 ± 1.82 vs. 1.9 ± 0.61, respectively; p < 0.0001). The median follow-up on living patients in this study was 41 months. NLR at the diagnosis was found to be an independent predictor for overall survival (OS) and event-free survival (EFS) by univariate and multivariate analysis. Patients with a NLR <2 at diagnosis experienced superior OS compared with patients with a NLR ≥2 (5-year OS rates were 87.5 and 42.4 %, respectively; p < 0.0001). In a similar fashion, superior EFS was observed in patients with a NLR <2 at the diagnosis compared with patients with a NLR ≥2 (5-year EFS rates were 88.4 and 41.8 %, respectively, p < 0.0001). This study suggests that NLR at the diagnosis is a simple, inexpensive, possible prognostic factor to assess clinical outcomes in MM patients.

[In Vitro Effect of Ankaferd Blood Stopper®, a Plant Extract Against Mycobacterium tuberculosis Isolates]. / Bir Bitki Ekstresi Olan Ankaferd Blood Stopper®'in Mycobacterium tuberculosis Izolatlarina Karsi In Vitro Etkinligi.

Treatment of drug-resistant Mycobacterium tuberculosis infections requires combination of anti-tuberculosis drugs which have several toxic side effects. Thus there is a need for safer and effective new drugs. Ankaferd Blood Stopper® (ABS), which is a mixture of plant extracts prepared from Alpinia officinarum, Glycyrrhiza glabra, Thymus vulgaris, Urtica dioica and Vitis vinifera, has homeostatic and antibacterial effects. Standard solutions of ABS are already being used topically for post-traumatic and post-operative bleeding control in our country. This study was aimed to evaluate the in vitro activity of ABS against M.tuberculosis isolates. A total of 57 clinical isolates [17 multidrug resistant (MDR), 11 resistant to only isoniazid (INH), one resistant to INH and streptomycin (STR), two resistant only to STR, two resistant only to ETM, and 24 susceptible to all drugs] and three standard strains [H37Rv (susceptible to all drugs), ATCC 35822 (INH-resistant), ATCC 35820 (STR-resistant)] were included in the study. Agar dilution method was used to detect the MIC values of ABS. In the study, ABS MIC value was determined as 10.94 µg/ml for M.tuberculosis H37Rv strain which was susceptible to all anti-tuberculosis drugs, whereas it was determined as 21.88 µg/ml for INH-resistant ATCC 35822 and STR-resistant ATCC 35820 strains. The MIC values for 24 susceptible clinical isolates were as follows; 10.94 µg/ml (n= 17), 21.88 µg/ml (n= 6) and < 1.37 µg/ml (n= 1). When evaluating 17 MDR clinical isolates, MIC values were determined as 5.47 µg/ml (n= 1), 10.94 µg/ml (n= 5) and 21.88 µg/ml (n= 11). MIC values were ranging between < 1.37-21.88 µg/ml among 11 INH-resistant isolates. These isolates were susceptible to other first line anti-tuberculosis drugs. MIC value of one isolate resistant to both of INH and STR was determined as 21.88 µg/ml. MIC value of the two sole STR-resistant isolates was 21.88 µg/ml. MIC values of the two sole ETM-resistant isolates were determined as 21.88 µg/ml and 10.94 µg/ml. MIC50 and MIC90 values for the tested bacteria were 10.94 µg/ml and 21.88 µg/ml, respectively. It was concluded that 16 fold diluted concentration of the topically used ABS solution was found to be active against tuberculosis bacilli in vitro. Thus ABS might be used as a supportive agent together with anti-tuberculous drugs during debridement of multiple drug-resistant M.tuberculosis caused osteomyelitis and lymphadenitis lesions.

Antimicrobial activity of plant extract Ankaferd Blood Stopper.

The in vitro antimicrobial activity of Ankaferd Blood Stopper (ABS) was assessed on 102 clinical isolates from both Gram negative and Gram positive bacteria and four standard strains, including MRSA ATCC 43300, MSSA ATCC 25923, P. aeruginosa ATCC 27853 and E. coli ATCC 35218. ABS was significantly active against all bacteria investigated.

Successful treatment of rheumatoid arthritis is associated with a reduction in serum sE-selectin and thrombomodulin level.

The aim of this study was to investigate the changes in serum levels of endothelial cell injury markers, soluble (s) E-selectin and thrombomodulin (TM), in patients with rheumatoid arthritis (RA) before and after antirheumatic drug treatment and to assess the relationship between these changes and clinical responses to the drug treatment. Eleven patients with RA having active arthritis and 12 healthy volunteers were enrolled in the study. They were monitored by clinical and laboratory parameters while receiving a combination of methotrexate, hydroxychloroquine and sulphasalazine. Pre- and post-treatment clinical and laboratory parameters, including sE-selectin and sTM levels, were measured. The ages of the patients were comparable with those of the control groups. Significant improvements were detected in erythrocyte sedimentation rate, C-reactive protein, hemoglobin, morning stiffness, patients' global assessment, physicians' global assessment, number of tender joints and number of swollen joints improved at the end of the therapy (for each parameter p < 0.05). Significant improvements were detected in clinical and laboratory parameters. In the patient group there were significant decreases in the levels of sTM and sE-selectin after treatment (p < 0.05). The patient group had significantly higher sTM and sE-selectin levels than the control group at the beginning of the study (p < 0.01), but the difference returned to normal after the treatment (p > 0.05). The sE-selectin and sTM levels significantly correlated with each other, and also with clinical and laboratory findings. Combination treatment successfully treated RA patients. sE-selectin and sTM levels probably reflect disease activity and can be helpful in monitoring disease status and response to therapy.

Bone marrow and peripheral blood C-kit ligand concentrations in patients with thrombocytosis and thrombocytopenia.

C-kit ligand (stem cell factor, SCF) is a hematopoietic growth factor with diverse effects. It has stimulatory effects on megakaryocytopoiesis acting in synergism with interleukin-3 (IL-3), thrombopoietin (TPO) and granulocyte-macrophage colony stimulating factor (GM-CSF). The relationship between SCF and megakaryocytopoiesis, especially the correlations between blood and bone marrow SCF levels have been not clearly established in the literature. We therefore, investigated peripheral and bone marrow SCF levels in patients with thrombocytosis and thrombocytopenia. Subjects were divided into three groups: those with (i) thrombocytopenia, (ii) thrombocytosis and (iii) healthy adults as controls. When the three groups were compared, the mean peripheral blood SCF level of the thrombocytosis group (2149±197) was significantly higher than the thrombocytopenia (1586±178) and normal control groups (1371±68; p<0.05) and the bone marrow SCF level was higher (2694±267) than the thrombocytopenia group (1700±182; p<0.05). In the correlation analysis, considering all the groups together the bone marrow and peripheral blood SCF concentrations were positively and significantly correlated (p<0.01; r=0.93). Correlations between platelet number and both bone marrow SCF concentration (p<0.01; r=0.51) and peripheral blood concentrations (p<0.01; r=0.40) were also shown. Our results indicate that SCF is operative in the pathological megakaryopoiesis of clonal origin and reactive thrombocytosis both in the local bone marrow microenvironment and the peripheral circulating blood. We feel that further studies on the platelet-SCF relationship and SCF levels in different disease states are required.

Is visual loss due to giant cell arteritis reversible?

Giant cell arteritis (GCA) is a common systemic vasculitis with an unknown etiology. It mainly affects people older than 50 years of age and often presents with symptoms such as headache, jaw claudication, visual loss, polymyalgia rheumatica and increased erythrocyte sedimentation rate (ESR). Established blindness is irreversible if the steroid treatment is not administered within a few days. Here, we report a case of GCA in a patient with a normal ESR whose left eye perceived just light at the initiation of treatment. Immediately prior to the combined treatment with high dose oral steroids and cyclophosphamide, the ESR level had increased to 80 mm/h and the vision improved after the combined treatment four months later.

Autoimmune hemolytic anemia in Philadelphia positive chronic myeloid leukemia with t(7;14) anomaly after 5 years of interferon alpha treatment.

A 41-year-old woman, Philadelphia positive chronic myeloid leukemia patient, had progressive decline in hemoglobin levels. She had been receiving interferon alpha treatment for five years. Autoimmune hemolytic anemia was diagnosed. Subsequent bone marrow examination revealed translocation t(7;14). She was placed on prednisone treatment. The patient responded to prednisone as treatment for the hemolytic process. The result of a direct Coombs' test remained positive. The patient died shortly after the diagnosis of autoimmune hemolytic anemia. Autoimmune hemolytic anemia should be considered in the evaluation of chronic myeloid leukemia patients with a sudden decrease in hemoglobin levels.

Circulating and local bone marrow renin-angiotensin system in leukemic hematopoiesis: preliminary evidences.

Until last the decade, the renin-angiotensin system (RAS) was considered as a circulating endocrine system. It is now known that there are local RASs in many tissues. It has also recently been hypothesized that there exists a local bone marrow (BM) RAS with paracrine/autocrine pathobiological functions. The aim of this study was to detect BM and peripheral blood levels of the essential RAS components in normal and leukemic hematopoiesis. Concentrations of renin and angiotensin-converting enzyme (ACE) were assayed in BM aspirates and in simultaneously drawn peripheral blood samples of 16 pre-chemotherapy leukemic and 10 post-treatment megaloblastic anemia patients with normal blood counts, as controls. In the leukemia group, the ACE concentration was found to be significantly higher in the BM (38+/-6.2 U/l) than in the peripheral blood (29.5+/-5.3 U/l), (p=0.029). In the leukemia group, although the BM renin concentration was higher than the peripheral blood levels (21.3+/-8.3 vs. 18.6+/-6.2 U/l), this difference was not statistically significant (p=0.196). In the control group, mean BM renin levels were insignificantly lower than in the peripheral blood (8.6+/-3 vs. 12.1+/-4.6 pg/ml) (p=0.059). In the leukemia group, serum ACE levels positively correlated with BM and peripheral blood blast percentages (p<0.05). Serum LDH level (p<0.01), BM blast (p<0.05) and peripheral blast percentages (p<0.01) were inversely correlated with serum potassium in the leukemia group.The results of this study can be considered as the preliminary evidence supporting the hypothesis of the presence of a local BM RAS. Further, molecular biologic and immunohistochemical studies are needed to shed light on this important subject. A better understanding of the interrelationships of RAS and hematopoiesis will bring new insights into the pathobiology and even novel therapies for such neoplastic diseases.

Circulating thrombopoietin in clonal versus reactive thrombocytosis.

INTRODUCTION: The aim of this study is to assess circulating thrombopoietin concentrations in patients with both clonal and reactive thrombocytosis (RT), which are two distinct categories of extreme platelet production circumstances. Investigation of the thrombopoietin levels in clonal versus reactive thrombocytosis may help us to understand the interactions of this key regulatory cytokine and the conditions in which abnormally increased platelet formation exist. MATERIALS AND METHODS: Thrombopoietin levels were measured in patients with platelet counts greater than 500 x1 0(3) microl(-1). The study population consisted of 21 patients with RT (13 with iron deficiency anemia, and 8 with rheumatoid arthritis), 24 patients with clonal thrombocytosis (six with essential thrombocytosis, three with myelofibrosis, eight with chronic myelogenous leukemia, and seven with polycythemia vera (PV)) and 16 healthy subjects were used as controls. RESULTS: The median plasma thrombopoietin concentration was 100.5 pg ml(-1) in patients with RT, 467 pg ml(-1) in patients with clonal thrombocytosis and 62.65 pg ml(-1) in the control group. The thrombopoietin concentration was found to be higher in the patients with primary thrombocytosis when compared to the control group (p=0.001), as well as in patients with RT (p=0.002). However, there was no statistically significant difference between the patients with RT and the control group (p=0.14). There was no correlation between thrombopoietin levels and the platelet counts in patients with clonal thrombocytosis, including essential thrombocythemia (ET). CONCLUSIION: Increased levels of thrombopoietin were found in patients with clonal thrombocytosis versus patients with RT and control subjects as well. Defective clearance of thrombopoietin by megakaryocytes and platelets due to a reduced number of thrombopoietin receptors may be the causative mechanism behind this. These results indicate that plasma thrombopoietin levels may be helpful in distinguishing between clonal and reactive thrombocytosis.