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OBJECTIVES Our aim was to identify factors associated with overall survival and the efficacy of postrelapse treatment protocols and to determine whether pretransplant consolidation therapy and minimal residual disease status pose a survival benefit. MATERIALS AND METHODS Patients with acute myeloid leukemia who underwent stem cell transplant between 2007 and 2018 were enrolled retrospectively. The effects of pretransplant cytogenetic and minimal residual disease status, pretransplant consolidation therapies, development of graft-versus-host disease, postrelapse treatment protocols, and type of con-ditioning regimens on overall survival were analyzed. RESULTS In 76 study patients, the cumulative overall 1- and 5-year relapse probabilities were 67.8% and 58.7%, respectively. Overall survival rates at 3 and 5 years in patients with and without relapse were 23.5% and 0% and 95.9% and 91.1% (P < .001), respectively. Although mean postrelapse overall survival was better with intensive salvage plus donor lymphocyte infusion, no significant differences were shown versus other therapies (intensive salvage, nonintensive salvage, intensive salvage or nonintensive salvage plus donor lymphocyte infusion, or supportive therapy). Twenty-three patients (30.3%) died during the study period with a median survival of 9.6 months. Patients with favorable, intermediate, and unfavorable cytogenetic status showed overall survival of 46.6 ± 10.4, 54.6 ± 4.4, and 36.9 ± 5.9 months (P = .807). Patients with and without minimal residual disease and patients who received or did not receive consolidation therapy had similar overall survival. Relapse was an independent predictor of overall survival (increased mortality risk of 26.22). Patients who developed graft-versus-host disease showed decreased relapse. CONCLUSIONS Relapse is the most important predictor of overall survival and is associated with poor prognosis. Pretransplant minimal residual status and cytogenetic status showed no effect on relapse rates and overall survival, and consolidation therapy did not improve outcomes.

Background Anemia is a frequent disorder worldwide. Iron deficiency anemia (IDA) is the most common form of anemia. Although oral iron is the first choice for treatment, the efficacy of oral iron preparations may be limited. Ferric carboxymaltose (FCM) is a novel parenteral iron preparation which can rapidly replenish iron stores. The aim of the present study is to investigate the impact of FCM dose on hemoglobin (Hb) and ferritin levels and the frequency of hypersensitivity reactions. Methods This study was conducted with 765 IDA patients between September 1, 2016 and September 1, 2018. He-moglobin (Hb), serum ferritin, transferrin saturation values were examined at the time of diagnosis, Hb and ferritin values at first month. Results Post-treatment Hb and ferritin levels significantly increased. The mean Hb level alteration was 2.43 ± 1.2 g/dL, the median ferritin level alteration was 157.3 ng/mL. The mean Hb level was lower and the mean change in Hb level was higher in higher doses. Allergic reactions were more frequent in higher doses. Conclusions Ferric carboxymaltose is a novel treatment option with a low risk of hypersensitivity reactions and well tolerated even in high doses.

The present study investigated the efficacy and safety profile of daratumumab monotherapy in 42 patients with relapsed refractory multiple myeloma through a Turkish early access program. the current findings have confirmed the efficacy of daratumumab monotherapy in heavily pretreated patients with refractory multiple myeloma because of the deep and durable responses and favorable safety and tolerability profile. Background: in countries where frontline drug approval is limited to first-generation proteasome inhibitors or immunomodulatory drugs, relapses have been both more frequent and less durable. We investigated real world data on the efficacy and safety of daratumumab monotherapy among patients with relapsed refractory multiple myeloma (RRMM) from Turkey using a prospective early access program. Patients and Methods: A total of 42 patients with RRMM after a minimum of 3 previous lines of proteasome inhibitor/immunomodulatory drug-based treatments were included from 25 centers across Turkey. Daratumumab monotherapy was administered intravenously at a dose of 16 mg/kg weekly (cycles 1-2), on alternate weeks (cycles 3-6), and monthly thereafter. Results: the median daratumumab monotherapy duration was 5.5 months (range, 0.2-28.7 months). the overall response rate was 45.2%, including 14 (33.3%) partial responses, 4 (9.5%) very good partial responses, and 1 (2.4%) complete response. the median duration of response was 4.9 months. the median progression-free survival (PFS) was 5.5 (95% confidence interval, 2.6-8.4 months) with 12- and 18-month PFS rates of 35.7% and 31.0%, respectively. the median overall survival was not reached; the 12- and 18-month overall survival rates were 64.3% and 59.5%, respectively. the depth of response had a significant effect on PFS (log-rank test, P = .026). Overall, of the 76 adverse events reported, 33 (43.4%) were grade >= 3; only 4 (9.52%) were grade 3 infusion-related reactions. No infusion-related reactions or adverse events led to treatment discontinuation. Conclusion: the present findings from our daratumumab early access program have confirmed the efficacy and safety profile of daratumumab monotherapy in heavily pretreated Turkish patients with RRMM., Janssen Pharmaceutica Turkey, The present daratumumab EAP was funded by Janssen Pharmaceutica Turkey. the authors would like to thank to Professor Sule Oktay, MD, PhD, and Cagla Ayhan, MD, from KAPPA Consultancy Training Research Ltd (Istanbul, Turkey), who contributed to the manuscript writing and statistical analyses.

Background Approximately half of patients with relapsed chemosensitive disease achieve robust responses with BEAM (BCNU, etoposide, cytarabine, and melphalan) and autologous stem cell rescue. The scarcity of comparative studies further limits alternative treatment protocols, such as the MITO/MEL (mitoxantrone, melphalan) protocol. Patients and Methods In this retrospective multicenter study, we compared the BEAM and MITO/MEL regimens used before autologous hematopoietic stem cell transplantation (ASCT) in terms of efficacy and side effects in patients with Hodgkin lymphoma. Data met international accreditation rules. Before ASCT, 108 patients received the MITO/MEL, and 34 patients received the BEAM. Results The median follow-up time was 36 months in the MITO/MEL group (range, 3-178) and 23 months in the BEAM group (range, 4-99). After ASCT, the 3-year expected overall survival and disease-free survival rates were 86.1% and 86.1% for the MITO/MEL group and 91.3% and 76.5% for the BEAM group, respectively. Although 50% of patients developed febrile neutropenia attacks in the MITO/MEL group, this rate was 91.1% in the BEAM group. The grade II and higher rates of hepatic, renal, gastrointestinal, and cardiac toxicities were similar in both groups. However, the rate of pulmonary toxicity was determined to be 1.9% in the MITO/MEL group and 29.4% in the BEAM group (P Conclusion The MITO/MEL conditioning regimen seems to be as effective as the BEAM regimen but has better tolerability in terms of pulmonary toxicity and may be used as an alternative option if necessary, depending on the comorbidity status of the patient.

Background Chronic myeloid leukemia (CML) is a disease resulting from BCR-ABL gene fusion. It is possible to monitor treatment by molecular testing for BCR-ABL. The lymphocyte-to-monocyte ratio (LMR) is a commonly used marker associated with prognosis in various neoplasms. This study was performed to evaluate the relevance of absolute lymphocyte count (ALC), absolute monocyte count (AMC), and LMR in predicting molecular response status in patients with chronic phase CML. Methods Samples submitted to our hematology laboratory for BCR-ABL testing between April 2012 and October 2018 were retrospectively reviewed. Concurrent hemogram testing together with the results of quantitative reverse transcriptase-polymerase chain reaction were noted. Data were grouped according to molecular response status and the ALC, AMC, and LMR were compared among patient groups. Results A total of 224 samples from 95 patients were included in the study. Analysis revealed differences between groups when newly diagnosed patients were compared with patients undergoing treatment, regardless of response status. However, analyzing the groups according to molecular response status failed to reveal differences in ALC, AMC, or LMR. Conclusions ALC, AMC, and LMR are not potential biomarkers for predicting molecular response status in patients with chronic phase CML.

Objective/background: Anti-T lymphocyte globulin Fresenius (rATG-F; ATG-Fresenius) and antithymocyte globulin (thymoglobulin), which are included in transplant protocols, are used to reduce the risk of chronic graft-versus-host disease (cGVHD) or suppress allograft rejection. Available clinical studies have been conducted in heterogenous patient populations and with different administration protocols including stem cell sources. Additionally, the pharmacokinetics of ATG is variable, and the clinically effective dose of rATG-F, in particular, is not exactly known. The aim of the study was to investigate the clinical outcomes of acute myeloid leukemia (AML) patients who underwent hemopoietic peripheral stem cell transplantation from full-matched sibling donors and given two different doses of r-ATG-F. Methods: This was a single-center, retrospective chart review conducted between July 2005 and July 2016. Sixty-nine consecutive AML patients who underwent transplant with fludarabine- and busulfan-based conditioning were included in the study. Patients in Group 1 received 15 mg/kg body weight rATG-F to 2013 (n = 46), and Group 2 received 30 mg/kg of rATG-F dose begining in 2013 to reduce to cGVHD (n = 23). Cyclosporine and methotrexate were used to treat acute GVHD (aGVHD) prophylaxis. Outcome parameters were compared between the groups. Results: Although the recommended dose r-ATG-F had led to a decrease in the cumulative incidence of cGVHD (27 [58.7%] vs. 8 [34.8%]; p = .03), it also increased the infection rate at 1 year (3 [6.5%] vs. 4 [17.4%]; p = .02). The two groups were similar in terms of engraftment time, aGVHD, relapse, nonrelapse mortality, and rATG-F-related toxicity. A Cox regression model revealed that aGVHD III–IV was associated with increased nonrelapse mortality at 1 year (hazard ratio = 18.2; 95% confidence interval, 1.667–199.255; p =

Adult patients with sickle cell disease (SCD) are highly susceptible to stem cell transplant complications, including drug toxicity, graft versus host disease (GVHD), and graft rejection due to SCD-related tissue damage, endothelial activation, and inflammation. The scarcity of compatible stem cells for transplantation further limits treatment options, with only 43 cases of adult allogeneic peripheral blood stem cell transplantation (allo-PSCT) from human leukocyte antigen (HLA)-identical sibling donors reported in the international registry for the period 1986-2013. Herein we report remarkable outcomes in a cohort of adult SCD patients who underwent allo-PSCT using a fludarabine (Flu), busulfan (Bu), and anti-T-cell lymphocyte globulin (ATG)-based conditioning regimen in combination with very low dose total body irradiation (TBI), followed by post-transplant cyclophosphamide (Cy) and sirolimus as GVHD prophylaxis. We performed a single-center, retrospective study consisting of 20 consecutive patients (mean age 33.4 years) who underwent allo-PSCT from HLA-matched related donors with a conditioning regimen of Flu 150/Bu 3.2/Cy 29/ATG 30 (Fresenius)/TBI 200 between September 2013 and September 2017. Data were validated by an independent data audit group of the affiliated JACIE-accredited transplantation center. All patients experienced a sustained donor cell engraftment. Full donor chimerism (total cell) occurred within 180 days in all patients. Mean duration of follow-up was 13.8 months (range: 0.3-50 months), with 12 (60%) patients completing 12 months. No non-relapse mortality or graft rejection occurred. Successful treatment was achieved without the presence of graft loss, grade III-IV acute GVHD, extensive chronic GVHD, or other major complications. Allo-PSCT in combination with Flu 150/Bu 3.2/Cy 29/ATG 30(Fresenius)/TBI 200- Cy/Sirolimus therapy yielded encouraging outcomes with no mortality and low incidence of GVHD. Further controlled studies will be necessary to compare transplant protocols and long-term outcomes.

Background and Objective Assessment of Hemoglobin S trait donors has gained importance together with the increased allogeneic peripheral stem cell transplant activity for sickle cell disease in the regions where the disease is prevalent. Outcomes of Granulocyte-Colony Stimulating Factor (G-CSF) administration are obscure for hemoglobin S trait donors. This study aims at investigating the incidence of hemoglobin S carrier status and outcomes of G-CSF administration among donors who live in Eastern Mediterranean region. Material and Method The cross-sectional, single-center cohort study was performed with 147 donors between January 2013 and March 2017. Prevalence of hemoglobin S trait was estimated and subjects with or without Hemogobin S trait were compared with regard to stem cell characteristics, early and late clinical outcomes after G-CSF administration. Results Eleven out of 147 donors (7.48%) were found as hemoglobin S trait. G-CSF administration was successfully completed and yielded good harvesting results in hemoglobin S trait donors. No statistically significant difference was found between groups with regard to early and late side effects, stem cell characteristics. Blood pressures and QTc values were within normal ranges in both groups. Groups were similar with regard to CD34 values. Conclusion G-CSF seems safe in hemoglobin S trait donors. Their being eligible as donors would increase the chance of the patients for allogeneic stem cell transplantation in high prevalence regions. Further studies are required to reveal the safety profile of G-SCF in hemoglobin S carriers in different regions.

Terlipressin is a synthetic vasopressin analogue that is used in the treatment of bleeding esophageal varices and hepatorenal syndrome in patients with cirrhosis. Hepatorenal syndrome is a form of renal failure seen in patients with cirrhosis, with fatal outcomes. Ischemic adverse effects related to terlipressin are rarely observed. Herein, two cases who developed ischemic skin necrosis due to terlipressin usage are presented. Terlipressin therapy was started in two cirrhotic patients with presumptive hepatorenal syndrome. During the therapy, ecchymotic and necrotic changes were observed on the scrotal regions of both patients. Skin lesions were relieved after terlipressin therapy. Biopsy results were consistent with ischemia. Even if seen rarely, possible emergence of ischemic complications must be considered.

To assess the role of first trimester maternal testosterone and dehydroepiandrosterone sulfate (DHEA-S) levels in prediction of development of gestational diabetes mellitus (GDM).Four hundred and fifty pregnant women were included in this prospective cohort study. All pregnant women with a singleton pregnancy who were not diabetic, had no family history of diabetes, had no history of previous GDM, were of white race and non-smokers were enrolled. Total testosterone and DHEA-S were measured at 11-14 weeks of gestation. The patients were called for routine pregnancy visits and followed accordingly. Forty-two patients did not come to their visits and were excluded. During gestational weeks 24-28, the remaining 408 patients were screened for GDM. The total testosterone and DHEA-S levels were compared between patients with and without GDM. Regression and receiver-operator curve analysis were performed.GDM developed in 22 women (5.7%). Compared with women without GDM, first trimester total testosterone levels were higher among women in whom GDM subsequently developed. The DHEA-S level did not differ. Age, total testosterone and body mass index were found to be independent predictors of GDM development. A total testosterone value of 0.45 ng/mL was found to predict development of GDM with a sensitivity of 63.6% and a specificity of 62.7%.First trimester total testosterone has a low testing power for GDM screening with low sensitivity and specificity values and cannot be used as a marker alone. It may have a role in combination with other markers.

Overt hypothyroidism is associated with an increased risk for developing cardiovascular disease. We aimed to assess the changes in renal function, serum lipids, vitamin B12, folic acid and homocysteine levels before and after treatment in hypothyroid patients.The study included 54 patients (F/M=47/7) with overt hypothyroidism. All patients were assessed for demographic characteristics such as age, gender, body weight, and body mass index. Fasting blood samples were taken from the patients for analysis of chemical parameters including thyroid stimulating hormone (TSH), free thyroxine (fT4), homocysteine, total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), folic acid, and vitamin B12 levels before and after L-thyroxine (LT4) treatment.Homocysteine levels in hypothyroidism (9.67 ± 5.24 mmol/l) were significantly higher than in euthyroid state (8.16 ± 3.38 mmol/L, p=0.038). Glomerular filtration rate (GFR) was lower before treatment. Following LT4 replacement, renal functions significantly improved. After achieving the euthyroid state, folic acid levels significantly increased although vitamin B12 levels were not changed. There was a significant reduction in serum lipid levels after LT4 replacement. It was demonstrated that there was a significant negative correlation between GFR and lipids and a positive correlation with homocysteine and lipids at hypothyroid state. After normalization of thyroid functions, the correlations became non-significant.The hypothyroidism was associated with increased serum homocysteine, lipids, and creatinine concentrations. The improvement of these parameters with LT4 replacement may be associated with the lower risk for atherosclerotic cardiovascular diseases in the patients with hypothyroidism.

Cardiac autonomic dysfunction may develop in patients with clinical or subclinical thyroid hormone deficiency. Heart rate variability (HRV) and heart rate turbulence (HRT) are used for evaluating changes in cardiac autonomic functions and also used to provide risk stratification in cardiac and noncardiac diseases. The aim of this study is to evaluate cardiac autonomic functions before and 6 months after thyroid replacement therapy in patients with thyroid hormone deficiency.Forty hypothyroid patients (mean age 48 ± 13, four male) and 31 healthy controls (mean age 51 ± 12, three male) were included in the study. Twenty-four hour ambulatory electrocardiogram recordings were taken using Pathfinder Software Version V8.255 (Reynolds Medical). The time domain parameters of HRV analysis were performed using the Heart Rate Variability Software (version 4.2.0, Norav Medical Ltd, Israel). HRT parameters, Turbulence Onset (TO), and Turbulence Slope (TS) were calculated with HRT! View Version 0.60-0.1 software.HRV and HRT parameters were decreased in the patient group (SDNN; P0.001, SDANN; P0.009, RMSSD; P = 0.049, TO; P = 0.035, TS; P0.001). After 6 months of thyroid replacement therapy, there were no significant changes observed in either HRV or HRT.Hypothyroidism may cause cardiac autonomic dysfunction. Treating hypothyroidism with L-thyroxine therapy does not effectively restore cardiac autonomic function. HRV and HRT can be used as to help monitor cardiovascular-related risk in this population.