Impact of posaconazole prophylaxis and antifungal treatment on BAL GM performance in hematology malignancy patients with febrile neutropenia: a real life experience.

BACKGROUND: Diagnostic accuracy of galactomannan measurements is highly variable depending on the study population, diagnostic procedures, and treatment procedures. We aimed to evaluate the effect of posaconazole prophylaxis and empiric antifungal treatment upon diagnostic accuracy of GM measurements in bronchoalveolar lavage (BAL), bronchial lavage (BL), and serum in hematological malignancy population. METHODS: Patients hospitalized in a single tertiary care center with hematologic malignancies undergoing fiberoptic bronchoscopy (FOB) with a preliminary diagnosis of IPA were retrospectively included. RESULTS: In all the study population (n = 327), AUC for BAL, BL, and serum GM were as follows: 0.731 [0.666-0.790], 0.869 [0.816-0.912], and 0.610 [0.540-0.676] with BL samples having the best diagnostic value. GM measurements in patients under posaconazole prophylaxis (n = 114) showed similar diagnostic performance. While specificity was similar between patients with and without posaconazole prophylaxis, sensitivity of GM measurements was lower in patients with prophylaxis. Analyses with patient classified according to antifungal treatment at the time of FOB procedure (n = 166) showed a decreased diagnostic accuracy in serum GM and BAL GM measurements related with the duration of treatment. However, BAL, BL, and serum GM measurements presented similar sensitivity and specificity in higher cut-off values in longer durations of antifungal treatment. CONCLUSION: Our study shows that posaconazole prophylaxis and active short-term (3 days) antifungal treatment do not significantly affect overall diagnostic performance of GM measurements in bronchoalveolar lavage and bronchial lavage samples. However, using different cut-off values for patients receiving active treatment might be suggested to increase sensitivity.

Systemic inflammatory indices for predicting prognosis of myelofibrosis.

The impact of inflammatory markers such as systemic immune-inflammation (SII) index and systemic inflammation response index (SIRI) on myelofibrosis (MF) prognosis was evaluated for the first time in this study. Data from 60 patients diagnosed with MF between March 2011 and September 2022 were retrospectively analyzed. In addition to disease-related markers, the impact of SII and SIRI on prognosis was evaluated. In our study, the overall median survival (OS) was 64 months. OS was significantly shorter in patients older than 65 years, with high ferritin and lymphocyte levels, transfusion dependence at diagnosis, platelet count below 100 × 109/L, Hb level below 8 g/dl, and high risk according to the dynamic international prognostic scoring system (DIPSS)-Plus score. When these variables were included in the multivariate Cox regression model, it was found that being older than 65 years, having a high ferritin value, being at high risk according to the DIPSS-plus score and Hb values below 8 increased the risk of death. Platelet-to-lymphocyte ratio (PLR) and SII index were lower in patients with a fatal outcome. No statistically significant relationship was found between SIRI and mortality. The findings of this study showed that low PLR and high ferritin were associated with poor prognosis in MF. Elevated SII and SIRI, evaluated for the first time in patients with myelofibrosis, did not predict prognosis. Since non-inflammatory variables play a role in the pathogenesis of MF, bone marrow indicators and systemic inflammation indicators derived from hematologic parameters may not be accurate.

Potential modifications of the PLASMIC scoring system for predicting thrombotic thrombocytopenic purpura: Sometimes, less is more.

INTRODUCTION: Thrombotic thrombocytopenic purpura (TTP) is a life-threatening occlusive disease of the microcirculation characterized by systemic platelet plugs, organ ischemia, deep thrombocytopenia, and fragmentation of erythrocytes. One of the widely used scoring system to determine the clinical probability of TTP is the PLASMIC scoring system. This study aimed to evaluate the contribution of PLASMIC score modifications to sensitivity and specificity in patients with microangiopathic hemolytic anemia (MAHA) undergoing plasma exchange with a prediagnosis of TTP at our center. MATERIALS AND METHODS: The data of patients who were hospitalized with a previous diagnosis of MAHA and TTP and underwent plasma exchange at Bursa Uludag University, Faculty of Medicine, Department of Hematology between January 2000 and January 2022 were retrospectively analyzed. RESULTS: Overall, 33 patients (including 15 and 18 with and without TTP, respectively) were included in this study. Receiver operating characteristic (ROC) analysis revealed that the area under the curve (AUC) for the original PLASMIC score was 0.985 (95% confidence interval [95% CI]: 0.955-1.000), and AUC for the PLASMIC score without mean corpuscular volume (MCV) was 0.967 (95% CI: 0.910-1.000), which is close to the original AUC. With the removal of MCV from the scoring system, the sensitivity decreased from 100% to 93%, whereas the specificity increased from 33% to 78%. CONCLUSIONS: Based on the results of this validation study, removing MCV from the PLASMIC score led to the categorization of eight non-TTP cases in the low-risk category, and this could avoid unnecessary plasma exchange. However, in our study increasing the specificity was at the expense of the sensitivity by missing one patient with this new scoring system without MCV. Further multicenter studies with large sample sizes are required owing to the fact that different parameters may be effective in TTP prediction among different populations.

The Role of White Blood Cell Count in Perianal Pathologies: A Retrospective Analysis of Hematologic Malignancies.

Background and Objective: Infections are the most common cause of anal and perianal pathologies in patients with hematological malignancies. Perianal infection diagnosis in this group of patients is difficult; thus, a careful anorectal examination is necessary with imaging modalities. In addition, the literature reveals a knowledge gap in the approach to anal pathologies in patients with neutropenia during diagnosis or chemotherapy. This study aimed to examine our institutional data on perianal complications and investigate the relationship between the white blood cell-neutrophil count, perianal lesion, and the type of treatment in patients with hematologic malignancies during the neutropenic period. Methods: Patients with a hematologic malignancy, hospitalized for cytotoxic chemotherapy, complicated by perianal pathology, documented by at least one imaging method, were included in the study. Results: A total of 42 patients were included in the study. Most of them had acute leukemia, 31 were affected by acute myeloid leukemia (AML), and 7 by Acute lymphoid leukemia (ALL). There was no statistically significant relationship between the anal abscess formation, the neutrophil count, and a previous perianal pathology. Anal abscess development was significantly more frequent in acute myeloid leukemia. An inverse relationship was found between the total white blood cell number at onset and having a surgical intervention for anal pathology.In conclusion, this article has shown that white blood cell count at the time of hospitalization can affect the surgical intervention in patients with hematological malignancy (in the majority with acute leukemia) affected by anal pathologies occurring in the neutropenic period.

The effect of comorbidities on the choice of tyrosine kinase inhibitors in patients with chronic myeloid leukemia.

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.

Is split-dose better than single-dose? Results of Turkish Stem Cell Coordination Center (TURKOK) donors in the era of rising biosimilar G-CSF.

BACKGROUND: Turkish Stem Cell Coordination Center (TURKOK) carries out the procurement process of unrelated allogeneic hematopoietic stem cells in Turkey. This study aims to compare the efficacy of both once-daily and divided-dose G-CSF administration and the original and biosimilar G-CSF use and the frequency and severity of adverse events in TURKOK donors. METHOD: The study was conducted retrospectively with 142 healthy TURKOK donors. For PBSC mobilization, two different subcutaneous G-CSF programs were used as 10 µ/kg/day single-dose and 5 µ/kg/12 h. Neupogen (Amgen, Puerto Rico) and Tevagrastim (Teva, Kfar Saba, Israel) were used as G-CSF. All donors started apheresis on the fifth day, and all side effects were recorded during the procedure. RESULTS: Stem cell yield was similar between single-dose and divided-doses based on donor weight, favoring the split-dose based on recipient weight (P = .506 and P = .023, respectively). Both G-CSF posologies were comparable if the target CD34+ cell yield was ≥4 × 106 /kg. CD34+ cell yield was equivalent when evaluated against recipient weight, significantly favoring Tevagrastim vs Neupogen by donor weight (P = .740 and P = .021, respectively). Side effects, duration of pain, and need for analgesia favor Tevagratim over Neupogen. CONCLUSION: Split-dose may be recommended for cases where the need for large numbers of CD34+ cells to be harvested is anticipated due to significant cell yield relative to recipient weight. However, sufficient hematopoietic stem cells can be collected with both posology. Tevagrastim is non-inferiority effective to Neupogen. Side effects during administration are both low-grade and temporary.

Evaluation of Using Empiric Glycopeptides in Accordance with the IDSA Guidelines in Hematologic Malignancy Patients with Febrile Neutropenia.

Background: This study aimed to evaluate the effects of the appropriate use of empiric glycopeptide therapy in hematologic malignancy patients with febrile neutropenia (FN). Materials and Methods: Patients with FN who were hospitalized in our clinic and started empiric glycopeptide therapy were retrospectively analyzed. Empiric glycopeptide treatment initial indications were determined according to 7 specific criteria in the IDSA guidelines. In addition, the duration of glycopeptide use according to initial indications, causative pathogens in culture positivity, frequency of VRE infection, and the mortality rate was identified. Results: 87 patients were included. Of these, 102 episodes of FN were analyzed. Appropriate use of glycopeptides was observed in 98% of patients. The most common initial indication for glycopeptide was skin or soft-tissue infection, with 52% (n = 53). The mean duration of glycopeptide use was 11 (2-22) days. The time of glycopeptide use was longer in patients with catheter-related infections than in those with severe mucositis and hemodynamic instability (p = 0,041/p = 0,016). The duration of glycopeptide use was shorter in patients with consolidation therapy than in those without consolidation therapy. The mortality rate in culture-positive patients was significantly higher than in culture-negative patients (p = 0.041). At 72 h, glycopeptide therapy was discontinued in 8 of 79 FN episodes within culture-negative patients. Conclusion: This study showed that the mortality rate was higher in culture-positive patients. Additionally, glycopeptides should be discontinued early with no evidence of gram-positive infection.

The evaluation of risk factors leading to early deaths in patients with acute promyelocytic leukemia: a retrospective study.

Acute promyelocytic leukemia (APL) differs from other forms of acute myeloid leukemia (AML), including coagulopathy, hemorrhage, disseminated intravascular coagulation (DIC), and treatment success with all-trans retinoic acid (ATRA). Despite ATRA, early deaths (ED) are still common in APL. Here, we evaluated factors associated with ED and applicability of scoring systems used to diagnose DIC. Ninety-one APL patients (55 females, 36 males, and median age 40 years) were included. ED was defined as deaths attributable to any cause between day of diagnosis and following 30th day. DIC was assessed based on DIC scoring system released by the International Society of Thrombosis and Hemostasis (ISTH) and Chinese Diagnostic Scoring System (CDSS). Patients' median follow-up time was 49.2 months, and ED developed in 14 (15.4% of) cases. Patients succumbing to ED had higher levels of the Eastern Cooperative Oncology Group Performance Status (ECOG PS), lactate dehydrogenase (LDH), and ISTH DIC, and lower fibrinogen levels (p <0.05). In multivariate Cox regression analysis, age >55 and ECOG PS ≥2 rates were revealed to be associated with ED. Based on ISTH and CDSS scores, DIC was reported in 47.3 and 58.2% of the patients, respectively. Despite advances in APL, ED is still a major obstacle. Besides the prompt recognition and correction of coagulopathy, those at high ED risk are recommended to be detected rapidly. Implementation of local treatment plans and creating awareness should be achieved in hematological centers. Common utilization of ATRA and arsenic trioxide (ATO) may be beneficial to overcome ED and coagulopathy in APL patients.

Patient characteristics and management practices in chronic myeloid leukemia in Turkey: reflections from an expert meeting.

INTRODUCTION: The therapeutic landscape of chronic myeloid leukemia (CML) has evolved significantly since the introduction of imatinib. The European LeukemiaNet (ELN) recommendations serve as a guide for diagnosis, treatment, and monitorization of CML, but availability and accessibility of diagnostic tools and medications affect their applicability. AREAS COVERED: This article provides an overview of the current clinical management of CML in Turkey with reference to the key outputs of the online expert meeting held in November 2020. The applicability of the ELN 2020 recommendations for treating CML in clinical practice was also discussed. EXPERT OPINION: Imatinib is the only reimbursed and the most preferred first-line treatment in CML restricting the upfront use of second-generation tyrosine kinase inhibitors (TKIs), thereby limiting the applicability of treatment-free remission approach in Turkey. The ELN recommendations about using the EUTOS Long-Term Survival (ELTS) score for risk assessment and focusing on patient reported outcomes and quality of life can be enhanced with educational activities. The widespread availability of standardized technical infrastructure for diagnosing and monitoring CML will contribute to better disease management. Establishing a sustainable national database for CML is valuable for observing patient characteristics and disease outcomes as well as the impact of treatment patterns over time.

Conventional Amphotericin B Associated Nephrotoxicity in Patients With Hematologic Malignancies.

INTRODUCTION:  Amphotericin B (AmB-d) is one of the most effective therapeutic options against frequently life-threatening systemic fungal infections in patients with hematologic malignancies. However, significant adverse effects including nephrotoxicity associated with its use limit its more widespread use. The objectives of our study were to determine the incidence of AmB-d associated nephrotoxicity, to evaluate clinical and epidemiological characteristics of patients, and to support the notion that conventional amphotericin B remains a valid therapeutic option among hematologic patients with proper patient selection. MATERIALS AND METHODS: A total of 110 patients with hematologic malignancies were admitted to our Hematology Unit between January 2014 and November 2017 who required anti-fungal therapy during intensive systemic chemotherapy. The incidence of AmB-d associated nephrotoxicity, side effect profile, time to nephrotoxicity, and clinical and epidemiological characteristics associated with treatment success were assessed retrospectively. RESULTS: Of the 110 patients receiving AmB-d, 70 (63.6%) were male and 40 (36.4%) were female. The mean age of participants was 44 years. The most common diagnosis was acute myeloid leukemia (n=53, 48.2%), and the most common chemotherapy protocol was 7 + 3 remission-induction (cytarabine 100 mg/m² days 1-7, Idarubicin 12 mg/m² days 1-3; n=24, 21.8%). In 56.4% of the patients, antifungal therapy was given empirically. In 40 patients (36.4%), nephrotoxicity was observed following antifungal treatment, and only four patients had stage 3 renal failure. The mean duration of time to nephrotoxicity from initiation of amphotericin B was four days (min: 2, max: 31). All patients were found to receive at least one additional potential nephrotoxic treatment during the antifungal treatment process.  Conclusion: AmB-d is associated with a significant risk of nephrotoxicity. In most hematological patients, antifungal treatment is initiated empirically, and patients received prolonged courses of treatment. Therefore, it is plausible to initiate such treatment with AmB-d, when one considers the already high treatment costs in this patient group as well as the fact that AmB-d offers similar efficacy to antifungal agents at a lower cost. AmB-d may be recommended as a first-line agent in this patient group with the introduction of newer and more costly antifungal agents when needed, on the basis of the fact that these patients can be closely monitored in a hospital setting, reversible nature of nephrotoxicity upon discontinuation, and rare occurrence of severe renal failure requiring dialysis.

Evaluation of clinical characteristics of patients with paroxysmal nocturnal hemoglobinuria treated with eculizumab in Turkey: a multicenter retrospective analysis.

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.

Identification of Psychological and Social Problems in Caregivers of Individuals Diagnosed with Hematologic Malignancy.

OBJECTIVE: Caring for patients with hematological malignancy could lead to many problems in different aspects regarding the lives of caregivers. However, there is limited data on the emotional and social problems of caregivers, who deal with patients of hematological malignancy. The aim of this study is to determine the emotional and social problems in caregivers of individuals diagnosed with hematological malignancy. METHODS: The study was carried out descriptively to identify the emotional and social problems in the relatives of the patients diagnosed with hematological malignancy as their caregivers, as well as the factors affecting these problems. The data of the study were collected with the Introductory Information Form and Identification of Emotional and Social Problems Form that were administered to the relatives of the patients. The data were evaluated by using Spearman's Rho correlation analysis and the Logit analysis in Statistical Package for the Social Sciences software. RESULTS: Among the caregivers, 59.8% were in the age group of 30-51 years, and 66.2% were female. Of the caregivers, 70.1% had difficulty in fulfilling their responsibilities. Spiritual distress had the highest score among the emotional problems, and experiencing caregiver strain had the highest score among the social problems. In the Logit model, the changes in the professional life was the variable that affects the emotional and social problems the most and significantly. In addition, emotional problems were affected by the financial problems at a statistically significant level. CONCLUSIONS: In this study, it is suggested that the caregivers should be provided with certain conveniences in their professional lives based on the fact that the problem, which affected emotional and social problems the most, is the change in the professional life; it is recommended that further studies should be carried out on the caregivers.

Evaluation of Sexual Dysfunction in Patients with Hematological Malignancies.

OBJECTIVE: Physiological and/or psychological problems that affect the quality of life of the patients occur depending on the diagnosis and treatment of hematological malignancies. Cancer treatment causes sexual problems such as infertility, vaginal dryness, and erectile dysfunction in the patients. Erectile dysfunction and loss of sexual desire are the most common sexual problems of men, while dyspareunia and loss of sexual desire are the most common sexual problems of women. This descriptive study was carried out to evaluate sexual problems and affecting factors in the patients with hematological cancer. METHODS: Between July 1, 2011, and July 31, 2011, 45 sexually active patients who volunteered to participate in the study and whose written consents were obtained were included in the study. The data of the study were collected using the descriptive characteristics form prepared by the researchers based on the relevant literature and the Arizona Sexual Experiences Scale (ASEX). The scale scores range from 5 to 30 and a score of >11 above indicates sexual dysfunction. RESULTS: Sexual dysfunction was observed in 62.2% of the patients. About 80.0% of women and 57.1% of men had sexual dysfunction. Sexual dysfunction was observed to be highest between the ages of 52-71 (81.2%) years. The mean total ASEX score was 15.90 ± 4.25 in women and 13.34 ± 5.37 in men. The ability to reach orgasm subscale score was found to differ by gender in the ASEX scale (P < 0.05). CONCLUSIONS: The prevalence of sexual dysfunction is high in the patients with hematological malignancies. It is recommended to evaluate these patients in terms of the presence of sexual dysfunction, as in the patients with other chronic diseases.

Efficacy and safety of ruxolitinib in patients with myelofibrosis: a retrospective and multicenter experience in Turkey

Background/aim: The aim of this study is to assess the efficacy and safety of ruxolitinib in patients with myelofibrosis. Materials and methods: From 15 centers, 176 patients (53.4% male, 46.6% female) were retrospectively evaluated. Results: The median age at ruxolitinib initiation was 62 (28­87) and 100 (56.8%) of all were diagnosed as PMF. Constitutional symptoms were observed in 84.7%. The median initiation dose of ruxolitinib was 30 mg (10­40). Dose change was made in 69 (39.2%) patients. Forty seven (35.6%) and 20 (15.2%) of 132 patients had hematological and nonhematological adverse events, respectively. The mean spleen sizes before and after ruxolitinib treatment were 219.67 ± 46.79 mm versus 199.49 ± 40.95 mm, respectively (p < 0.001). There was no correlation between baseline features and subsequent spleen response. Overall survival at 1-year was 89.5% and the median follow up was 10 (1­55) months. We could not show any relationship between survival and reduction in spleen size (p = 0.73). Conclusion: We found ruxolitinib to be safe, well tolerated, and effective in real-life clinical practice in Turkey. Ruxolitinib dose titration can provide better responses in terms of not only clinical benefit but also for long term of ruxolitinib treatment.

Vancomycin-resistant enterococci infection and predisposing factors for infection and mortality in patients with acute leukaemia and febrile neutropenia.

BACKGROUND: Vancomycin-resistant enterococcus (VRE) is an infectious agent that can increase morbidity and mortality, especially in patients with neutropenia in haematology departments. We analysed VRE infections and mortality rates among VRE colonized patients with acute leukaemia, defined predisposing risk factors for infection and mortality, and investigated the influence of daptomycin or linezolid treatment on mortality. PATIENTS-METHODS: We included 200 VRE colonized adult acute leukaemia patients with febrile neutropenia between January 2010 and January 2016. Data were collected from electronic files. RESULTS: There were 179 patients in the colonized group, and 21 patients in the infected group. Enterococcus faecium (van A) was isolated from all patients. The infection rate was 10.5 %, and the types of infections noted were as follows: bloodstream (n = 14; 66.7 %), skin and soft tissue (n = 3; 14.3 %), urinary (n = 2; 9.5 %), and others (9.5 %). In the multivariate logistic regression analysis, exposure to invasive procedures, coinfection status, and >15 days of VRE positivity were independent risk factors for VRE infections. In hospital mortality rates were 57.1 % in the infected group, and 9.5 % in the colonized group (p < 0.001). Older age, female gender, absolute neutropenia, and coinfection status were statistically significant predictor of survival. CONCLUSION: Vancomycin-resistant enterococcus infections are associated with high morbidity and mortality in haematology patients with neutropenia. Clinicians should be aware of predisposing risk factors for VRE infection to avoid unfavourable outcomes. We believe that larger studies are necessary regarding the influence of treatment with daptomycin and linezolid.

Study for the Diagnostic Screening of Paroxysmal Nocturnal Hemoglobinuria in Older Patients with Unexplained Anemia and/or Cytopenia.

BACKGROUND: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired hematopoietic stem cell disease that may lead to weakness and death of patients, if unrecognized and untreated. Although consensus guidelines were reviewed recently for the diagnostic screening of PNH with multi-parameter flow cytometry (FCM), until now, no study has investigated the efficiency of such clinical indications in older patients. METHODS: Overall, 20 centers participated in the study and a total of 1,689 patients were included, 313 of whom were at geriatric age and 1,376 were aged 18 - 64 years. We evaluated the efficiency of consensus clinical indications for PNH testing using FCM in peripheral blood samples and compared the results of older patients and patients aged 18 - 64 years. RESULTS: PNH clones were detected positive in 7/313 (2.2%) of the older patients. Five (74.4%) of the patients with PNH clones had aplastic anemia, 1 had unexplained cytopenia, and 1 patient had myelodysplastic syndrome (MDS) with refractory anemia. PNH clones were not detected in any older patients who were screened for unexplained thrombosis, Coombs (-) hemolytic anemia, hemoglobinuria, and others (e.g., elevated lactate dehydrogenase (LDH), splenomegaly). We detected PNH clones in 55/1376 (4%) samples of the patients aged under 65 years. Forty-two (76.4%) patients with PNH clones had aplastic anemia, 2 patients had Coombs (-) hemolytic anemia, 3 patients had unexplained cytopenia, 1 patient had MDS with refractory anemia, 1 patient had hemoglobinuria, and 6 (10.9%) had others (e.g., elevated LDH, splenomegaly). PNH clones were not detected in any patients who were screened for unexplained thrombosis. There was no statistical difference between the geriatric population and patients aged 18 - 64 years in terms of clinical indications for PNH screening with FCM (p = 0.49). CONCLUSIONS: Our results showed that the current clinical indications for PNH screening with FCM were also efficient in older patients. We suggest that older patients with unexplained anemia, myelodysplastic syndrome with refractory anemia, and unexplained cytopenia should be screened for PNH with FCM to identify patients who would benefit from treatment.

Patterns of Hydroxyurea Prescription and Use in Routine Clinical Management of Polycythemia Vera: A Multicenter Chart Review Study

Objective: This study aimed to evaluate real-life data on patterns of hydroxyurea prescription/use in polycythemia vera (PV). Materials and Methods: This retrospective chart review study included PV patients who had received hydroxyurea therapy for at least 2 months after PV diagnosis. Data were collected from 10 representative academic medical centers. Results: Of 657 patients, 50.9% were in the high-risk group (age ≥60 years and/or history of thromboembolic event). The median duration of hydroxyurea therapy was 43.40 months for all patients; 70.2% of the patients had ongoing hydroxyurea therapy at last follow-up. Hydroxyurea was discontinued in 22.4% of the patients; the most common reason was death (38.5%). The predicted time until hydroxyurea discontinuation was 187.8 months (standard error: ±21.7) for all patients. This duration was shorter in females (140.3±37.7 vs. 187.8±29.7) (p=0.08). This trend was also observed in surviving patients aged ≥50 years at hydroxyurea initiation (122.2±12.4 vs. 187.8±30.7, p=0.03). Among the patients who were still on hydroxyurea therapy, 40.3% had a hematocrit concentration of ≥45% at their last follow-up visit, and the rate of patients with at least one elevated blood cell count was 67.8%. Conclusion: Hydroxyurea prescription patterns and treatment aims are frequently not in accordance with the guideline recommendations. Its discontinuation rate is higher in females.

Study for the diagnostic screening of paroxsymal nocturnal hemoglobinuria in Turkey: Prospective multicentric evaluation of suspected patients.

BACKGROUND: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disease presenting with variable and various clinical findings. PNH might be overlooked and diagnosis may be delayed due to low awareness about PNH. This is the first multicenter study in Turkey, investigating the efficiency of diagnostic screening of PNH by multiparameter flow cytometry (FCM) according to consensus guidelines. METHODS: We evaluate the efficiency of consensus clinical indications for PNH testing with FCM in 1689peripheral blood samples from 20 centers between January 2014 and December 2017. RESULTS: Overall, at the 20 centers contributing to this study, PNH clone were detected in 62/1689 samples (3.6%) by FCM test. 75.8% (n = 47) of patients with PNH clone had aplastic anemia, 3.2% (n = 2) had Coombs (-) hemolytic anemia, 6.5% (n = 4) had unexplained cytopenia, 3.2% (n = 2) had MDS with refractory anemia, 1.6% (n = 1) had hemoglobinuria and 9.7% (n = 6) had others (elevated LDH, splenomegaly, etc.). In contrast, we detect no PNH clone test in patients who were screened for unexplained thrombosis. CONCLUSIONS: Our study showed that current clinical indications for PNH testing are highly efficient and diagnostic screening of suspected patients for PNH with FCM is recommended. However, advanced screening algorithms are required for patients presenting with unexplained thrombosis and normal complete blood count.

Community-acquired Lower Urinary Tract Infections: Etiology, Antimicrobial Resistance, and Treatment Results in Female Patients.

BACKGROUND/PURPOSE: Most community-acquired urinary tract infections (UTIs) are usually treated empirically. The knowledge of antibiotic resistance patterns of the microorganisms causing UTI is essential for defining the empirical treatment. OBJECTIVE: The aim of the present study is to determine the distribution of bacterial strains isolated from lower UTIs and their resistance patterns against commonly used antimicrobial agents and treatment results in female patients. SUBJECTS AND METHODS: This is a retrospective analysis of medical case records of 90 female patients with lower UTI for a period of 4 years from January 2013 to December 2016 in a tertiary care hospital in the Trakya region of Turkey. RESULTS: The most common causative agent was Escherichia coli (66.6% of cases) followed by Klebsiella pneumoniae (16.6%). Fosfomycin was the most active agent against E. coli (resistant isolates: 5.5%), followed by nitrofurantoin (resistant isolates: 7.4%). Extended-spectrum beta-lactamases (ESBLs) production was observed in 29 (32.2%) isolates (22 in E. coli, 6 in K. pneumoniae, and 1 in Enterobacter spp.). The antimicrobial resistance rates among ESBL-producing E. coli isolates for trimethoprim-sulfamethoxazole, ciprofloxacin, fosfomycin, and nitrofurantoin were 77.7%, 72.7%, 13.6%, and 18.2%, respectively (P < 0.05). The estimated microbiological eradication rates for nitrofurantoin and fosfomycin were 89.7% and 83.8%, respectively. CONCLUSIONS: The results of the present study indicate that nitrofurantoin and fosfomycin may be considered for empirical therapy of lower UTIs in Trakya region of Turkey.

Polycythemia vera: diagnosis, clinical course, and current management

Very important developments related to polycythemia vera (PV) have occurred during the last two decades. The discovery of Janus kinase (JAK) 2 mutations has changed both the diagnosis and clinical management of PV. Currently JAK2 molecular testing is essential in the diagnostic work-up and JAK2 mutation positivity is a major diagnostic criterion. The discovery of JAK2 mutations suggested that abnormal JAK-STAT signaling was a pivotal feature in the pathogenesis of Philadelphia-negative myeloproliferative neoplasms. This idea led to the development of JAK inhibitors. Currently ruxolitinib, a JAK1/JAK2 inhibitor, is also approved for PV patients with hydroxyurea resistance or intolerance. International collaborations have made it possible to describe disease characteristics and evolution better. Presently it is possible to quantify the symptomatic burden of the disease and to estimate prognosis. In spite of these developments, management of PV still largely depends on estimation of thromboembolic risk and trying to decrease the risk with or without cytoreductive medications. Different approaches have been proposed by international disease experts for the diagnosis, thromboembolic risk estimation, and drug selection. This paper aims to review clinical aspects of PV and propose a management algorithm. The authors also point to still unresolved questions and unmet needs in diagnosis and management.