Functions of the endothelium and its role in hematopoietic cell transplantation.

The endothelium is a single-layered structure that responds to physical and chemical signals with various factors it synthesizes. In the early days of its discovery, as the inner wall of the vessels, the endothelium was thought to be a simple barrier that lays on the surface. Over time it is discovered that endothelium maintains body homeostasis with the molecules it synthesizes, despite its simple single-layer structure. It has been accepted as an important organ that contributes to the maintenance of vascular tone, cell adhesion, inflammation, vascular permeability and coagulation. Any imbalance in these physiological and pathological events causes endothelial dysfunction. This can cause many diseases such as atherosclerosis, hypertension, diabetes, or it can occur because of these. Endothelial related disorders may also complicate hematopoietic stem cell transplantation (HSCT), which is used to treat various hematologic and neoplastic diseases. These life-threatening complications include graft-versus-host disease, hepatic veno-occlussive disease, transplant-associated thrombotic microangiopathy and diffuse alveolar hemorrhage. They share a similar pathophysiology involving endothelial cells with different clinical presentations. Therefore, current researche on the issue is putting the endothelium under the spotlight for novel markers and treatment options that should be used to monitor or treat at least some of these complications following HSCT.

Efficacy and Safety of Ibrutinib Therapy in Patients with Chronic Lymphocytic Leukemia: Retrospective Analysis of Real-Life Data

Objective: This study aimed to retrospectively evaluate the efficacy, safety, and survival outcome of single-agent ibrutinib therapy in chronic lymphocytic leukemia patients. Materials and Methods: A total of 136 patients (mean age ± standard deviation: 64.6±10.3 years, 66.9% males) who had received at least one dose of ibrutinib were included in this retrospective multicenter, noninterventional hospital-registry study conducted at 33 centers across Turkey. Data on patient demographics, baseline characteristics, laboratory findings, and leukemia-cell cytogenetics were retrieved. Treatment response, survival outcome including overall survival (OS) and progression-free survival (PFS), and safety data were analyzed. Results: Overall, 36.7% of patients were categorized as Eastern Cooperative Oncology Group (ECOG) class 2-3, while 44.9% were in Rai stage 4. Fluorescence in situ hybridization revealed the presence of del(17p) in 39.8% of the patients. Patients received a median of 2.0 (range: 0-7) lines of pre-ibrutinib therapy. Median duration of therapy was 8.8 months (range: 0.4-58.0 months). The 1-year PFS and OS rates were 82.2% and 84.6%, respectively, while median PFS time was 30.0 (standard error, 95% confidence interval: 5.1, 20.0-40.0) months and median OS time was 37.9 (3.2, 31.5-44.2) months. Treatment response (complete or partial response), PFS time, and OS time were better with 0-2 lines versus 3-7 lines of prior therapy (p<0.001, p=0.001, and p<0.001, respectively), with ECOG class 0-1 versus class 2-3 (p=0.006, p=0.011, and p=0.001, respectively), and with Rai stage 0-2 versus 3-4 (p=0.002, p=0.001, and p=0.002, respectively). No significant difference was noted in treatment response rates or survival outcome with respect to the presence of comorbidity, bulky disease, or del(17p). While 176 adverse events (AEs) were reported in 74 (54.4%) patients, 46 of those 176 AEs were grade 3-4, including pneumonia (n=12), neutropenia (n=11), anemia (n=5), thrombocytopenia (n=5), and fever (n=5). Conclusion: This real-life analysis confirms the favorable efficacy and safety profile of long-term ibrutinib treatment while emphasizing the potential adverse impacts of poorer ECOG performance status, heavy treatment prior to ibrutinib, and advanced Rai stage on patient compliance, treatment response, and survival outcomes.

Significance of Lymphocyte Count, Monocyte Count, and Lymphocyte-To-Monocyte Ratio in Predicting Molecular Response in Patients with Chronic Myeloid Leukemia: a Single-Centre Experience.

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.

A Novel Simplified Combination of Monoclonal Antibodies for Flow Cytometric Analysis of Bronchoalveolar Lavage Samples.

BACKGROUND: The profile of leukocytes in bronchoalveolar lavage (BAL) fluid provides important information for diagnosing various lung diseases. A differential cell count of BAL is conventionally performed by evaluating centrifuged samples under a light microscope and enumerating the stained cells. Another rarely used method to identify BAL leukocytes is flow cytometry (FCM). However, there are no guidelines for standardizing this method and related literature is limited. This study aimed to evaluate the accuracy of FCM for identifying BAL leukocytes. METHODS: The BAL samples accepted to the hematology laboratory between 2014 - 2018 were retrospectively evaluated via light microscopy (LM) by a hematologist; while flow cytometric analyses with a monoclonal antibody panel composed of CD45/CD14/CD16 were noted by another doctor. The percentages of macrophages, lymphocytes, neutrophils and eosinophils determined by both methods were recorded for analysis. Correlations between the results from LM and FCM were investigated. In addition, compatibility between LM and FCM for denoting pathological values for each cell type was checked. RESULTS: Among 140 reviewed BAL samples, 76 were included for further analysis. Comparisons revealed strong correlations between FCM and LM for identifying macrophages, lymphocytes, neutrophils, and eosinophils. In addition, regarding the normal cutoff values for each leukocyte type, FCM and LM were similar in the identification of pathological changes of all cell types except eosinophils. CONCLUSIONS: Flow cytometry was found to be feasible for use instead of LM and might become a more widely used technique to analyze BAL fluid in the future.

A Multi-Center Study on the Efficacy of Eltrombopag in Management of Refractory Chronic Immune Thrombocytopenia: A Real-Life Experience

Objective: The aim of the present study was to evaluate the efficacy and safety of eltrombopag, an oral thrombopoietin receptor agonist, in patients with chronic immune thrombocytopenia (ITP). Materials and Methods: A total of 285 chronic ITP patients (187 women, 65.6%; 98 men, 34.4%) followed in 55 centers were enrolled in this retrospective cohort. Response to treatment was assessed according to platelet count (/mm3) and defined as complete (platelet count of >100,000/mm3), partial (30,000-100,000/mm3 or doubling of platelet count after treatment), or unresponsive (<30,000/mm3). Clinical findings, descriptive features, response to treatment, and side effects were recorded. Correlations between descriptive, clinical, and hematological parameters were analyzed. Results: The median age at diagnosis was 43.9±20.6 (range: 3-95) years and the duration of follow-up was 18.0±6.4 (range: 6-28.2) months. Overall response rate was 86.7% (n=247). Complete and partial responses were observed in 182 (63.8%) and 65 (22.8%) patients, respectively. Thirty-eight patients (13.4%) did not respond to eltrombopag treatment. For patients above 60 years old (n=68), overall response rate was 89.7% (n=61), and for those above 80 years old (n=12), overall response rate was 83% (n=10). Considering thrombocyte count before treatment, eltrombopag significantly increased platelet count at the 1st, 2nd, 3rd, 4th, and 8th weeks of treatment. As the time required for partial or complete response increased, response to treatment was significantly reduced. The time to reach the maximum platelet levels after treatment was quite variable (1-202 weeks). Notably, the higher the maximum platelet count after eltrombopag treatment, the more likely that side effects would occur. The most common side effects were headache (21.6%), weakness (13.7%), hepatotoxicity (11.8%), and thrombosis (5.9%). Conclusion: Results of the current study imply that eltrombopag is an effective therapeutic option even in elderly patients with chronic ITP. However, patients must be closely monitored for response and side effects during treatment. Since both response and side effects may be variable throughout the follow-up period, patients should be evaluated dynamically, especially in terms of thrombotic risk factors.

Efficacy and safety of eltrombopag in treatment-refractory primary immune thrombocytopenia: a retrospective study.

Eltrombopag was used in patients with chronic primary immune thrombocytopenia (ITP) who did not tolerate or were refractory to two or more previous treatments. The primary aims of the study were to determine the efficacy and safety of long-term eltrombopag treatment. Data were extracted from medical chart records retrospectively. Platelet count of at least 50 000/µl at any time point during the treatment was defined as the 'response'. Median duration of eltrombopag treatment was 29 weeks (11-74). The number of patients who had a platelet count of at least 50 000/µl at any time point was 26 (83.9%). The response was achieved by the second week in most of the patients. Concomitant ITP medications were withdrawn in nine out of the 11 patients. Eltrombopag was discontinued in one patient due to sustained response despite discontinuation of the treatment. Age, sex, concomitant ITP treatments, and previous ITP treatment failures had no impact on the treatment response. The treatment was discontinued due to thrombosis in only four patients. Four patients experienced a minor bleeding event. Hepatotoxicity and all other adverse events were mild and manageable. Eltrombopag is effective, safe, and well tolerated in the long-term treatment of chronic ITP patients.

Aplastic anemia associated with oral terbinafine: a case report and review of the literature.

Onychomycosis (OM) is a common fungal infection of the toenails and/or fingernails that is highly prevalent in the general population and also responsible for significant morbidity. OM is caused by dermatophytes, nondermatophytic molds, or yeast. Today systemic antifungal agents are considered as the gold standard for all types of OM. Here we report a case of aplastic anemia associated with oral terbinafine use and a review of the literature on hematological toxicities associated with terbinafine.