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Multiple myeloma (MM) is one of the plasma cell-related hematological malignancies exceeding 10.0% of all marrow cells, and they make a paraprotein that is a marker of the disease. Myeloma is one of the most common types of hematological malignancies in humans. Genetic bio-markers have been used for prognostic markers in patients diagnosed with MM. The genetic and genomic changes have been identified using karyotyping, fluorescent in situ hybridization (FISH), next generation sequencing (NGS), specifically whole-genome sequencing or exome sequencing. Circulatory plasma cells, circulating free DNA (cfD-NA) and microRNAs (miRNAs) comprised in liquid biopsy are potentially used in diagnosis/prognosis of MM. In this study, we analyzed and compared results of karyo-typing, FISH and NGS in 35 MM cases. Diagnostic strategies are expanding rapidly and newly developed NGS-based testing may help the understanding of the complexities of genetic alterations in karyotypically normal cases.

Background: Hemophilia B (HB), an X-linked recessive inherited bleeding disorder, exhibits a high prevalence among males., Objectives: To present the first national cohort of persons with HB to define the demographics, clinical characteristics, and treatment patterns in Turkey., Methods: This multicenter, retrospective study included 433 alive persons with HB registered in 35 centers between 1961 and 2018. Analyses were performed by age subgroups (0-17 years, 18-64 years, and ≥65 years), disease severity by factor levels (severe, <1 IU/dL; moderate, 1-5 IU/dL; mild, >5 IU/dL). Additionally, patients were stratified based on the initiation year of follow-up at the relevant study center, creating 2 periods: 1993-2006 (referred to as period A) and 2007-2018 (referred to as period B)., Results: Predominantly male (98.6%), the median age at data entry was 22.1 years ( n  = 429). The majority (49.0%) had moderate HB, followed by severe (30.0%) and mild (15.7%) disease. Of the 377 patients with complete treatment details, 209 (55.4%) were under prophylaxis from their diagnosis onwards, while 79 patients (21.0%) only received on-demand treatment. Additionally, 89 patients (23.6%) initially underwent on-demand treatment and later were switched to prophylaxis. Knees were the primary site of bleeding and the most frequently intervened joints. Most of the major (47.5%) and minor (53.3%) orthopedic procedures were carried out in persons with severe HB, while half of radioactive synovectomy procedures were performed on persons with moderate HB., Conclusion: This paper describes the demographics, clinical characteristics, and treatments patterns of a large cohort of alive persons with HB on a national scale., (© 2024 The Authors.)

The Myeloproliferative Neoplasm Symptom Assessment Total Symptom Score (MPN-SAF TSS) is a surrogate marker for symptom evaluation in chronic myeloproliferative neoplasms (MPNs). However, insufficient data are available regarding the relationship among the MPN-SAF TSS, JAK2 mutation allele burden, and thrombosis. In this retrospective analysis, we aimed to determine the genetic burdens, clinical features, and relationships with MPN-SAF TSS in MPN patients. One hundred thirty JAK2 V617F-positive patients with MPNs were included in our study. We calculated the MPN-SAF TSS for all patients and compared it with their clinical characteristics. Patients with higher JAK2 V617F mutation allele burden had higher MPN-SAF TSS values (p=0.008). Patients with thrombosis had higher MPN-SAF TSS than patients without thrombosis (p=0.003). The mean MPN-SAF TSS was higher in patients with primary myelofibrosis compared to those with polycythemia vera and essential thrombocythemia. Thrombosis was associated with increased symptom severity in several domains, including fatigue, abdominal discomfort, inactivity, night sweats, pruritus, weight loss, and early satiety. Additionally, an increase in JAK2 allele burden was observed with higher symptom scores. The MPN-SAF TSS proved to be a reliable tool for assessing symptom burden in Turkish MPN patients. Furthermore, the significant association between thrombosis occurrence and symptom severity suggests that thrombotic events may contribute to symptom development. Notably, increasing JAK2 allele burden was correlated with more severe symptoms, highlighting its potential role in predicting disease burden. This study emphasizes the importance of symptom assessment in MPN patients and supports the incorporation of the MPN-SAF TSS in routine clinical practice to enhance patient care and management., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors., (©Copyright 2024 by Turkish Society of Hematology Turkish Journal of Hematology, Published by Galenos Publishing House.)

Objective: Primary immune thrombocytopenia (ITP) is an acquired disorder of platelets with a complex and unclear mechanism of increased immune destruction or impaired production of platelets. While the management of ITP is evolving, there is still a need for guidance, particularly in certain circumstances such as pregnancy, emergencies, or patients requiring co-medications. We aimed to determine the tendencies of hematologists in Türkiye in the event of such special considerations., Materials and Methods: Applying a modified Delphi method, the Turkish National ITP Working Group, founded under the auspices of the Turkish Society of Hematology, developed a questionnaire consisting of statements regarding pregnancy, emergencies, and circumstances requiring co-treatment with antiaggregants or anticoagulants. A total of 107 hematologists working in university or state hospitals voted for their agreement or disagreement with the statements for two sequential rounds., Results: The participating hematologists reached an agreement on starting treatment for pregnant patients with platelets of less than 30x10 9 /L and delivery either vaginally or by cesarean section being safe at platelet counts above 50x10 9 /L. For emergencies and the rescue management of ITP, the panel agreed against the use of high-dose corticosteroids alone, preferring combinations with transfusions or intravenous immunoglobulin. For patients who require interventions, platelet counts of >50x10 9 /L were regarded as safe for low-risk procedures as well as co-treatment with antiplatelets or anticoagulants., Conclusion: As the National ITP Study Group, we have observed the need to increase the practice guidance regarding patients with primary ITP requiring additional treatments including invasive interventions and co-treatments for coagulation. Decisions on the management of ITP during pregnancy should be individualized. There is a lack of consensus on the thresholds of platelet counts as well as co-morbidities and co-medications. This lack of consensus may be due to variations in practices., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors., (©Copyright 2024 by Turkish Society of Hematology Turkish Journal of Hematology, Published by Galenos Publishing House.)

Objective: Primary immune thrombocytopenia (pITP) is an acquired autoimmune disorder related to the increased destruction and/or impaired production of platelets. Its diagnosis and management are challenging and require expertise and the interpretation of international consensus reports and guidelines with national variations in availability. We aimed to assess the agreement of hematologists in Türkiye on certain aspects of both first-line and second-line management of patients with pITP., Materials and Methods: Applying a modified Delphi method, the Turkish National ITP Working Group (14 steering committee members), founded under the auspices of the Turkish Society of Hematology, developed a 21-item questionnaire consisting of statements regarding the first-line and second-line treatment of pITP. A total of 107 adult hematologists working in either university or state hospitals voted for their agreement or disagreement with the statements in two consecutive rounds., Results: The participants reached consensus on the use of corticosteroids as first-line treatment and with limited duration. Methylprednisolone was the corticosteroid of choice rather than dexamethasone. Use of intravenous immunoglobulin was not preferred for patients without bleeding. It was also agreed that thrombopoietin receptor antagonists (TPO-RAs) or rituximab should be recommended as second-line treatment and that splenectomy could be considered 12-24 months after diagnosis in patients with chronic pITP., Conclusion: The optimization of the dose and duration of TPO-RAs in addition to corticosteroids is necessary to improve the management of patients with pITP., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors., (©Copyright 2024 by Turkish Society of Hematology Turkish Journal of Hematology, Published by Galenos Publishing House.)

Objective: In recent years, new developments have been incorporated into daily practice in the management of immune thrombotic thrombocytopenic purpura (iTTP). In particular, clinical scoring systems could help clinicians with clinical decision-making and early recognition. However, older patients frequently present with more organ involvement and in unusual ways. The ways in which age could affect these clinical prediction scoring systems remain unclear. We evaluated the use of PLASMIC and French scores in patients over 60 years of age., Materials and Methods: We performed a retrospective cross-sectional analysis of patients over 60 years of age with a presumptive diagnosis of iTTP between 2014 and 2022 at 10 centers. We calculated PLASMIC and French scores and compared our data with a single-center analysis of younger patients presenting with thrombotic microangiopathy., Results: Our study included 30 patients over 60 years of age and a control group of 28 patients younger than 60 years. The diagnostic sensitivity and specificity of a French score of ≥1 were lower in older patients compared to the control group (78.9% vs. 100% and 18.2% vs. 57.1%, respectively). The diagnostic sensitivity and specificity of a PLASMIC score of ≥5 were 100% vs. 95% and 27.3% vs. 100% for the study group and control group, respectively. Our study showed a higher mortality rate in older patients compared to the control group (30% vs. 7.1%, p=0.043)., Conclusion: For a limited number of patients (n=6), our results showed that rituximab can reduce mortality. Given that the reliability of clinical prediction scores for iTTP in older patients may be lower, more caution must be undertaken in interpreting their results., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors., (©Copyright 2023 by Turkish Society of Hematology Turkish Journal of Hematology, Published by Galenos Publishing House.)

Bernard Soulier Syndrome (BSS) is an inherited bleeding disorder characterized by macrothrombocytopenia and absence of ristocetin-induced platelet aggregation. Clinical findings vary from person to person. Most of the patients are diagnosed with muco-cutaneous bleeding such as purpura, epistaxis and gingival bleeding in early childhood. Few pregnant women with BSS are described in the literature. Management of thrombocytopenia during pregnancy and delivery requires a multidisciplinary approach. The family should be warned about the potentially life-threatening bleeding during pregnancy and the delivery and the decision about mode of delivery should be individualised, involving discussion with patient and multidisciplinary team., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

This survey study aimed to evaluate the level of awareness and knowledge of acquired hemophilia A (AHA) among physicians from various specialties. Data were collected by administering a questionnaire containing questions about two patient profiles to evaluate the approaches of physicians from different specialties. The study included a total of 945 physicians. The most common suspected diagnosis for the clinical patient profile was immune thrombocytopenia, followed by hemophilia. For the laboratory patient profile, the most common suspected diagnosis was hemophilia. While only 9.4% of the physicians stated that they had good knowledge of this disease, only 21.6% wanted to learn more about AHA. Most of the participating physicians do not rank AHA first in the differential diagnosis of a patient with clinical and laboratory findings of AHA. Appropriate educational activities to raise awareness of AHA will help reduce disease-related morbidity and mortality., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors., (©Copyright 2023 by Turkish Society of Hematology Turkish Journal of Hematology, Published by Galenos Publishing House.)

Objective: In immune thrombocytopenia (ITP), which is a common acquired bleeding disorder, cytotoxic T-cell-mediated cellular immune response against both circulating platelets and bone marrow megakaryocytes are the most important mechanisms in the pathogenesis., Methods: In our study, we evaluated the features of 33 patients with ITP, over 80 years of age., Results: The median age of the patients was 90, 15 patients were female (45.4%). The mean platelet count of the patients was 39×10 9 /L and the mean mean platelet volume was 10,33fL. Twelve patients had a target thrombocyte count greater than 30×10 9 /L, while 20 patients had a target platelet count of 75×10 9 /L or greater with an absolute indication of antiaggregation. In the environmental spread, 18 dysplasia findings were observed., Conclusion: Morphologic observations suggesting dysplasia including micromegakaryocytes and a non-dysplastic but dysmegakaryopoietic finding, multiple segmented nuclei may be related to the degree of thrombocytopenia and response to treatment. Likewise, nondysplastic features including immature forms, emperipolesis, bare nucleus, hypolobulation, and hypersegmented nucleus were related to the degree of thrombocytopenia., Competing Interests: No conflict of interest was declared by the authors., (© Copyright 2023 by Istanbul Provincial Directorate of Health.)

Background: Central nervous system (CNS) prophylactic options for diffuse large B-cell lymphoma (DLBCL) are administered differently in most centers. Unfortunately, there is still not a consensus on which patients, which regimen, for how many cycles, and when prophylaxis should be administered. Thus, this remains an unmet clinical need., Methods: We administered a survey study under the Lymphoma Scientific Subcommittee of the Turkish Society of Haematology. The questions were directed to hematologists through the monkey survey system., Results: The CNS International Prognostic Index score is a factor that clinicians frequently use when deciding on prophylaxis and is considered reliable. Although the perspective on anatomical risk factors is similar to that reported in the literature, breast involvement is still considered a critical risk factor in Turkey. Participants considered double or triple hit and double/triple expressor lymphoma as significant risk factors. Various methods have been used to demonstrate CNS relapses. Intrathecal prophylaxis is the preferred method., Conclusion: There are diverse methodological and technical ideas. The controversial results reported in the literature on the effectiveness of CNS prophylaxis may explain this finding. Although CNS prophylactic methods for patients with DLBCL are still controversial, the effect of secondary CNS involvement on survival is inevitable. Standard practices followed by national guidelines may be effective in reducing the variety of application methods and creating homogeneous results for efficacy and survival follow-up studies.

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

Variants in the UNC45A cochaperone have been recently associated with a syndrome combining diarrhea, cholestasis, deafness, and bone fragility. Yet the mechanism underlying intestinal failure in UNC45A deficiency remains unclear. Here, biallelic variants in UNC45A were identified by next-generation sequencing in 6 patients with congenital diarrhea. Corroborating in silico prediction, variants either abolished UNC45A expression or altered protein conformation. Myosin VB was identified by mass spectrometry as client of the UNC45A chaperone and was found misfolded in UNC45AKO Caco-2 cells. In keeping with impaired myosin VB function, UNC45AKO Caco-2 cells showed abnormal epithelial morphogenesis that was restored by full-length UNC45A, but not by mutant alleles. Patients and UNC45AKO 3D organoids displayed altered luminal development and microvillus inclusions, while 2D cultures revealed Rab11 and apical transporter mislocalization as well as sparse and disorganized microvilli. All those features resembled the subcellular abnormalities observed in duodenal biopsies from patients with microvillus inclusion disease. Finally, microvillus inclusions and shortened microvilli were evidenced in enterocytes from unc45a-deficient zebrafish. Taken together, our results provide evidence that UNC45A plays an essential role in epithelial morphogenesis through its cochaperone function of myosin VB and that UNC45A loss causes a variant of microvillus inclusion disease.

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., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Patients with solid malignancies are more vulnerable to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection than the healthy population. The outcome of SARS-CoV-2 infection in highly immunosuppressed populations, such as in patients with hematological malignancies, is a point of interest. We aimed to analyze the symptoms, complications, intensive care unit admissions, and mortality rates of patients with hematological malignancies infected with SARS-CoV-2 in Turkey., Materials and Methods: In this multicenter study, we included 340 adult and pediatric patients diagnosed with SARS-CoV-2 from March to November 2020. Diagnosis and status of primary disease, treatment schedules for hematological malignancies, time from last treatment, life expectancy related to the hematological disease, and comorbidities were recorded, together with data regarding symptoms, treatment, and outcome of SARS-CoV-2 infection., Results: Forty four patients were asymptomatic at diagnosis of SARS-CoV- 2 infection. Among symptomatic patients, fever, cough, and dyspnea were observed in 62.6%, 48.8%, and 41.8%, respectively. Sixty-nine (20%) patients had mild SARS-CoV-2 disease, whereas moderate, severe, and critical disease was reported in 101 (29%), 71 (20%), and 55 (16%) patients, respectively. Of the entire cohort, 251 (73.8%) patients were hospitalized for SARS-CoV-2. Mortality related to SARS-CoV-2 infection was 26.5% in the entire cohort; this comprised 4.4% of those patients with mild disease, 12.4% of those with moderate disease, and 83% of those with severe or critical disease. Active hematological disease, lower life expectancy related to primary hematological disease, neutropenia at diagnosis of SARS-CoV-2, ICU admission, and first-line therapy used for coronavirus disease-2019 treatment were found to be related to higher mortality rates. Treatments with hydroxychloroquine alone or in combination with azithromycin were associated with a higher rate of mortality in comparison to favipiravir use., Conclusion: Patients with hematological malignancy infected with SARS-CoV-2 have an increased risk of severe disease and mortality.

Objective: Eltrombopag remains a prominent option in the treatment of steroid-dependent or steroid-refractory immune thrombocytopenia (ITP) patients. Unfortunately, not all patients respond to eltrombopag. Antinuclear antibody (ANA) positivity can be seen at rates of up to 30% in ITP patients. Despite being widely used, more markers to predict the response to eltrombopag are still needed. In the present study, we aimed to show the association between ANA positivity and eltrombopag response in ITP patients., Materials and Methods: Patients who were diagnosed with ITP in the Trakya University Faculty of Medicine’s Department of Hematology and who underwent eltrombopag treatment due to their resistance to steroids and other treatments were included in our study. ANA measurement was performed by indirect fluorescent antibody method and titers of 1:160 and above were considered positive. ANA measurements were made before starting eltrombopag., Results: Forty-five patients were included in our study, 33 being women and 12 men. The mean age of the patients was 45.73 years. There were 14 patients with ANA positivity and 31 patients were found to be ANA-negative. Response rates were higher in ANA-negative patients compared to ANA-positive patients in the 1 st and 6 th months of eltrombopag treatment (p<0.05)., Conclusion: ANA positivity in ITP may indicate unresponsiveness to eltrombopag treatment, a finding that should be further supported by prospective studies involving more patients.

Objective: Several clinical scoring systems have been developed for the differential diagnosis of thrombotic microangiopathies (TMAs), all to predict and identify patients with ADAMTS13 deficiency and to start treatment as soon as possible. The first scoring system in this regard was the Bentley score, and the French score and PLASMIC score were developed afterwards., Materials and Methods: We aimed to evaluate the laboratory parameters and clinical features of patients who underwent plasma exchange with a prediagnosis of TTP at our clinic between 2007 and 2019 and whose ADAMTS13 enzyme levels were measured and to compare the findings with the scoring systems., Results: Data of 35 patients were evaluated. Twelve patients were evaluated as high risk according to all three scoring systems. A statistically significant relation was observed between all three scoring systems and ADAMTS13 levels., Conclusion: A moderate correlation was found between all three scoring systems and ADAMTS13 levels. We observed similar potential strength of all three scoring systems to predict TTP among other TMAs and we conclude that they are applicable in daily practice.

Myosin Vb (MYO5B) is a motor protein that facilitates protein trafficking and recycling in polarized cells by RAB11- and RAB8-dependent mechanisms. Biallelic MYO5B mutations are identified in the majority of patients with microvillus inclusion disease (MVID). MVID is an intractable diarrhea of infantile onset with characteristic histopathologic findings that requires life-long parenteral nutrition or intestinal transplantation. A large number of such patients eventually develop cholestatic liver disease. Bi-allelic MYO5B mutations are also identified in a subset of patients with predominant early-onset cholestatic liver disease. We present here the compilation of 114 patients with disease-causing MYO5B genotypes, including 44 novel patients as well as 35 novel MYO5B mutations, and an analysis of MYO5B mutations with regard to functional consequences. Our data support the concept that (1) a complete lack of MYO5B protein or early MYO5B truncation causes predominant intestinal disease (MYO5B-MVID), (2) the expression of full-length mutant MYO5B proteins with residual function causes predominant cholestatic liver disease (MYO5B-PFIC), and (3) the expression of mutant MYO5B proteins without residual function causes both intestinal and hepatic disease (MYO5B-MIXED). Genotype-phenotype data are deposited in the existing open MYO5B database in order to improve disease diagnosis, prognosis, and genetic counseling.

Advanced diagnostic methods give an advantage for the identification of abnormalities in myeloid malignancies. Various researchers have shown the potential importance of genetic tests before the disease's onset and in remission. Large testing panels prevent false-negative results in myeloid malignancies. However, the critical question is how the results of conventional cytogenetic and molecular cytogenetic techniques can be merged with NGS technologies. In this paper, we drew an algorithm for the evaluation of myeloid malignancies. To evaluate genetic abnormalities, we performed cytogenetics, molecular cytogenetics, and NGS testing in myeloid malignancies. In this study, we analyzed 100 patients admitted to the Medical Genetics Laboratory with different myeloid malignancies. We highlighted the possible diagnostic algorithm for cytogenetically normal cases. We applied NGS 141 gene panel for cytogenetically normal patients, and we detected two or more pathogenic variations in 61 out of 100 patients (61%). NGS's pathogenic variation detection rate varies in disease groups: they were present in 85% of A.M.L. and 23% of M.D.S. Here, we identified 24 novel variations out of total pathogenic variations in myeloid malignancies. A total of 18 novel variations were identified in A.M.L., and 6 novel variations were identified in M.D.S. Despite long turnaround times, conventional techniques are still a golden standard for myeloid malignancies but sometimes cryptic gene fusions or complex abnormalities cannot be easily identified by conventional techniques. In these conditions, advanced technologies like NGS are highly recommended., Competing Interests: Competing interests: The authors declare no conflict of Interest.

Objective: Invasive fungal infections (IFI) are important and trending causes of mortality in patients with acute leukemia, especially during the remission induction., Methods: In this study, 225 patients who were diagnosed with acute myeloid leukemia (AML) and undergoing intensive treatment for remission induction were enrolled in a retrospective manner., Results: Within the whole group, which consisted of 225 patients, 90 patients received prophylactic antifungal treatment (PAT) (40%), while 135 patients did not (60%) receive. The mean cost of hospitalization was 9.151,6 (2.872,6-20.483,3) US dollars. Gender distribution and mean ages of groups were similar. One hundred fourteen patients not on PAT (84.4%) and five patients on PAT (5.5%) received intravenous antifungal treatment. Thirty-two of the patients who were not on PAT (23.7%) and 11 of the patients on PAT died during remission induction (12.22%). The mean day of the hospitalization was 22.61 days for the patients on PAT and 33.89 days for the patients who were not on PAT. In patients on PAT, the mean number of transfused platelet units was six (0-9), while 12.51 (4-43) units for patients who were not on PAT., Conclusion: In our study, the oral suspension form of posaconazole was observed to be cost-effective to prevent IFI with a significant decrease in mortality during remission induction treatment., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors., (Copyright: © 2020 by Istanbul Northern Anatolian Association of Public Hospitals.)

Risk assessment in newly diagnosed multiple myeloma patients (NDMM) is the first and the most crucial determinant of treatment. With the utilization of FISH analysis as a part of routine practice, high risk Multiple Myeloma (MM) is defined as having at least one of the mutations related with poor prognosis including; t(4;14) t(14;16), t(14;20), del 17p, p53 mutation, gain 1q and del 1p. M-Smart MM risk stratification guideline by Mayo Clinic has proposed a concept similar to high grade lymphomas. Having two of the high risk genetic abnormalities were defined as double hit MM and having any three as triple hit MM. Based on these definitions which may bring a much more clinically relatable understanding in MM prognosis, we aimed to assess our database regarding these two concepts and their probable significance in terms of outcome and prognosis. We retrospectively evaluated 159 newly diagnosed multiple myeloma patients and their clinical course. Among these patients; twenty-four patients have one high risk determinant and also seven and two patients were classified as double hit MM and triple hit MM respectively. Overall survival (OS) of the patients with double hit MM was 6 months, 32.0 months for patients with single high risk abnormality and 57.0 months for patients with no high risk abnormality. Univariate analysis showed that Double Hit and Triple Hit MM is a predictive of low OS. Hazard Ratio of patients with one high risk abnormality was 1.42, double-hit MM patients was 5.55, and triple-hit MM patients was 7.3. Despite the development of novel drugs and their effects of prolonging survival, the treatment has not been individualized. Understanding the biology of each patient as a unique process will be the success of the treatment. As it is known that some MM patients harbor high risk genetic abnormalities according to FISH analysis, we can continue the argument that some patients bring an even higher risk and that can be defined as double or triple hit MM.

Aims: Hereditary hemorrhagic telangiectasia is an autosomal dominant disorder characterized by telangiectasia, epistaxis, and vascular malformations. Pathogenic mutations were found in ENG, AVCRL1, SMAD4 , and GDF genes. In this study, we present our database of patients with hereditary hemorrhagic telangiectasia regarding the phenotype-genotype relations and discuss two novel ENG gene pathogenic variations in two unrelated families., Methods: Next Generation Sequencing analysis was performed on the peripheral blood of nine patients with hereditary hemorrhagic telangiectasia in four unrelated families. All patients were diagnosed with hereditary hemorrhagic telangiectasia according to the Curaçao criteria. Data on treatment and screenings of visceral involvement were recorded from files., Results: We have found a pathogenic variation in either the ENG or ACVRL1 gene in each family. Two novel pathogenic variations in the ENG gene, including NM&#95;000118.3 (ENG): c.416delC (p.P139fs*24) and NM&#95;000118.3(ENG): c.1139dupT (p.Leu380PhefsTer16), were found in the same family. The NM&#95;000020.2(ACVRL1): c.1298C>T (p.Pro433Leu) pathogenic variation in the ACVRL1 gene in our first family and a novel heterozygous likely pathogenic NM&#95;000020.2(ACVRL1): c.95T>C (p.Val32Ala) variation was found in our second family. Seven of the nine patients were treated with thalidomide for controlling bleeding episodes. All patients responded to thalidomide. In one patient, the response to thalidomide was lost and switched to bevacizumab., Conclusion: In HHT certain type of mutations correlates with disease phenotypes and with next generation sequencing method, new pathogenic variations can be revealed which might help managing HHT patients.

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 (/mm 3 ) and defined as complete (platelet count of >100,000/mm 3 ), partial (30,000-100,000/mm 3 or doubling of platelet count after treatment), or unresponsive (<30,000/mm 3 ). 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 1 st , 2 nd , 3 rd , 4 th , and 8 th 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.

Chronic lymphocytic leukaemia (CLL) is a heterogeneous disease with uncertain course. Treatment should be tailored to the patient's disease as well as the prognostic subgroup. With the increased use of rituximab as well as other selective and non-selective immunomodulatory agents, the incidence of infectious complications and second malignancies has also increased. Progressive multifocal leucoencephalopathy (PML) is a complication of rituximab in HIV-negative patients. A 56-year-old male with CLL had been treated and relapsed four times in 6 years. Rituximab was added to the combination after the second relapse and repeated in the third relapse in combination with bendamustine. In the seventh year of diagnosis, relapse of CLL and an ulcerated tumorous lesion was observed in the left index finger, which progressed in 3 months and was later diagnosed as angiosarcoma. The cancer was treated with local radiotherapy and combination chemotherapy. One year after the last rituximab exposure, progressive muscle weakness developed and polyoma JC virus DNA was observed with increased titres in the cerebrospinal fluid, and the patient was diagnosed as having PML. The patient died 2 months later. Our patient had an unusual course of CLL over 8 years, with relapses, complicated with a secondary malignancy and an infectious complication., Competing Interests: None

Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominantly inherited disorder characterized by bleeding episodes. These episodes tend to happen spontaneously and reduce the quality of life. Patients are often unresponsive to local measures. With the pathophysiological role of angiogenesis in HHT, antiangiogenic drugs including thalidomide are used to control bleeding episodes. In our study, we evaluated 6 patients with HHT, calculating their Epistaxis Severity Score (ESS) and performing a quality of life assessment with the 36-Item Short Form Health Survey Questionnaire (SF-36), and we studied the alterations of these evaluations with thalidomide treatment. Three patients were male and three were female. Mean age was 60.50 years. No side effects were observed during the treatment period. Improvements of certain SF-36 dimensions including physical functioning, physical component summary, and mental component summary and of the ESS were observed after treatment. Thalidomide may be effective to control bleeding episodes with a reasonable tolerance profile in patients with HHT.

Background: Certolizumab pegol is used to treat ankylosing spondylitis, Crohn’s disease, psoriatic arthritis, and rheumatoid arthritis. Unlike other monoclonal antibodies such as infliximab and adalimumab, certolizumab does not contain an Fc fraction and hence does not induce complement activation. In this report, we describe the case of a patient with thrombotic microangiopathy caused due to certolizumab pegol, with a brief description about the pathophysiological approach to thrombotic microangiopathy., Case Report: A-39-year-old man suffering from ankylosing spondylitis for the past 10 years presented with fatigue. He had been on certolizumab pegol treatment for 6 months, starting with 400 and 200 mg every 2 weeks. He had significant nonimmune hemolytic anemia and thrombocytopenia without a disseminated intravascular coagulopathy. Schistocytes were observed in more than 10% of the erythrocytes per field. Plasma exchange along with corticosteroid treatment was started. There was a dramatic improvement within a week, and after 10 sessions of plasma exchange, the patient was discharged on corticosteroids with a tapering plan. ADAMTS13 enzyme activity was determined to be normal., Conclusion: The development of drug-induced thrombotic microangiopathy may be either immune-mediated or dose-dependent toxicity-mediated Anti-drug antibodies and their immunological aspects are still unclear and yet to be elucidated.

This consensus report includes expert opinions and recommendations regarding the screening, and if necessary, the follow-up, prophylaxis, and treatment of hepatitis B before the treatment in patients who will undergo immunosuppressive therapy due to an emergency risk of hepatitis B reactivation. To increase awareness regarding the risk of hepatitis B reactivation in immunosuppressive patients, academicians from several university health research and training centers across Turkey came together and discussed the importance of the subject, current status, and issues in accordance with the current literature data and presented solutions.

Objective: Vancomycin-resistant enterococci (VRE) are common pathogens of hospital-acquired infection. Long hospitalization periods, use of broad-spectrum antibiotics, and immunosuppression are major risks for VRE colonization. We aimed to evaluate patients' characteristics and factors that may contribute to VRE colonization., Materials and Methods: Data of 66 patients with colonization and 112 patients without colonization who were hospitalized in the hematology clinic were collected. Hematological malignancies, preexisting gastrointestinal complaints, the presence of hypogammaglobulinemia at the time of diagnosis, complications like neutropenic enterocolitis (NEC), and Eastern Cooperative Oncology Group (ECOG) and Karnofsky performance statuses were recorded., Results: Ages of the patients ranged between 19 and 95 years (mean: 55.99). Karnofsky and ECOG scores were statistically related to VRE colonization (p<0.000 and p<0.000), though only the Karnofsky score was significant based on logistic regression analysis. Almost all patients with acute leukemia (45 patients) had been on antibiotics (piperacillin-tazobactam, ceftazidime, and meropenem), while no patients with myelodysplastic syndrome, myeloma, or benign diseases and 2 patients with lymphoma and 1 with chronic myeloid leukemia were on antibiotics. Median time for colonization regardless of antibiotic use and diagnosis was 4.5 days (range: 3-11 days). In the VRE-colonized group, 40.9% of patients had NEC development, while in the non-colonized group, only 1.7% had NEC development. In the VRE-colonized group 46 patients (69.7%) and in the non-colonized group 27 patients (24.1%) had hypogammaglobulinemia at diagnosis; among these patients, 23 patients in the VRE-colonized group (50%) had a B-cell malignancy (lymphoma, myeloma, or chronic lymphocytic leukemia)., Conclusion: Besides already anticipated diseases like leukemia, B-cell malignancies are also at high risk for colonization. This proclivity may be attributed to lack of gastrointestinal IgA due to hypogammaglobulinemia. Prolonged hospitalization (>7 days) may also be accepted as a risk factor, independent of diagnosis or antibiotic use. Performance status is also an important factor for colonization, which may be related to poorer hygiene and increased external help.

Competing Interests: No conflict of interest was declared by the authors.

Objective/background: Myelodysplastic syndromes (MDSs) are a group of monoclonal hematopoietic diseases consisting of a number of various entities. The presence of differences in chromosomal content of cells within the same individual is known as chromosomal mosaicism. The impact of mosaic pattern on the prognosis of MDS has been unclear. In this study, we aimed to determine the impact of mosaic pattern on the survival of patients with MDS., Methods: We retrospectively evaluated 119 patients diagnosed with MDS at the Trakya University Faculty of Medicine, Department of Hematology. Giemsa-Trypsin-Giemsa banding was used to evaluate chromosomal abnormality. The effect of chromosomal abnormality mosaicism on overall survival and transformation to acute leukemia was evaluated by Kaplan-Meier survival analysis., Results: The mean age at diagnosis was 66.3years, and the mean disease duration was 24.2months. Chromosomal abnormality was observed in 32.5% of patients. Patients with chromosomal abnormalities comprising at least 50% metaphases had significantly lower overall survival than patients with abnormality comprising up to 50% of all abnormal metaphases (p=.003). There were no differences in transformation to acute leukemia among patients with higher and lower chromosomal mosaicism (p=.056)., Conclusion: The most important outcome of this study was to demonstrate worse overall survival rates in MDS patients with higher abnormal chromosomal mosaicism than patients with lesser abnormal chromosomal mosaicism. Higher levels of abnormal chromosomal mosaicism did not predict transformation to acute leukemia. The cause of worse outcomes of patients with higher abnormal chromosomal mosaicism may be related to clonal mass., (Copyright © 2016 King Faisal Specialist Hospital & Research Centre. Published by Elsevier Ltd. All rights reserved.)

The association between pediatric celiac disease (CD) and atherosclerosis is unknown. Our aim was to investigate whether pediatric CD patients have an increased risk of atherosclerosis. We evaluated the premature atherosclerosis by pulse wave velocity (PWV) and carotid intima-media thickness (cIMT). A total of 37 CD patients (20 girls, mean age 13±3.3 years) and 36 healthy age and sex matched controls were enrolled. Mean duration of CD was 47.1±32.3 months and 40.5% of patients had positive tissue transglutaminase antibody (tTg) IgA. Total cholesterol level was lower in CD (p=0.026) and cIMT was lower in tTg IgA antibody negative CD (p=0.030). cIMT was significantly correlated with tTg IgA antibody positivity (r=0.336; p=0.042). Adherence to strict gluten-free diet is associated with decreased cIMT, suggesting that gluten withdrawal seems to have a beneficial effect on premature atherosclerosis.

Introduction: The risk of developing insulin resistance and metabolic syndrome is particularly high in central obesity. In this study we evaluated the effects of fat distribution and some adipokines on insulin resistance in prediabetic patients., Material and Methods: Eighty-seven age- and sex-matched patients were divided into three groups according to their 75-gram oral glucose tolerance test results as follows: impaired fasting glucose group, impaired glucose tolerance group, and normal glucose tolerance group. Fasting insulin levels were measured. Homeostatic model assessment of insulin resistance was calculated. Body fat mass measurements were assessed by bioelectric impedance analyser and abdominal fat thicknesses (subcutaneous, visceral, and preperitoneal) by ultrasonography. The fasting serum levels of several adipokines [adiponectin, leptin, resistin, vaspin, visfatin, retinol-binding protein-4 (RBP-4), tumour necrosis factor-alpha (TNF-alpha)] were measured by ELISA method., Results: The mean body mass index, fat mass measurements, and abdominal fat thicknesses of the groups were similar. There were no differences between groups in terms of the mean fasting insulin, vaspin, RBP-4, leptin, resistin, and TNF-alpha. In comparison of the prediabetic and normal groups, the levels of adiponectin (p < 0.001) and visfatin (p < 0.001) were lower in the prediabetic group. Furthermore, we found that high body mass index (p < 0.01) and fat mass (p < 0.01) and low adiponectin (p < 0.05) levels have roles in the development of insulin resistance in the prediabetic group., Conclusions: We suggested that in the prediabetic period not only obesity but also decreased adiponectin levels play some role in the pathogenesis of insulin resistance. (Endokrynol Pol 2016; 67 (3): 277-282).

Objective: Growth arrest-specific 6 (Gas6) is a newly discovered vitamin K-dependent protein, which is a ligand for TAM receptors [Tyro3 (Sky), Axl, and Mer] from the tyrosine kinase family. Gas6 knockout mice were resistant to venous and arterial thrombosis. There are contradictory reports on the presence of Gas6 and its receptors in mouse platelets. The objective of this study was to investigate whether Gas6 and its receptors were present in mouse platelets or not., Materials and Methods: Specific pathogen-free BALB/c male and female mice of 8-10 weeks old and 25-30 g in weight were anesthetized under light ether anesthesia and blood samples were taken from their hearts. RNAs were isolated from isolated platelets, and then mRNAs encoding Gas6 and TAM receptors were detected by reverse transcription-polymerase chain reaction (RT-PCR). Protein concentrations of Gas6 and TAM receptors in platelets were measured by ELISA, but not those of Mer, because of the absence of any commercial ELISA kit for mouse specimens., Results: RT-PCR results indicated the presence of mRNAs encoding Gas6 and Mer in mouse platelets. However, although RT-PCR reactions were performed at various temperatures and cycles, we could not detect the presence of mRNAs encoding Axl and Tyro3 (Sky). Receptor protein levels of Axl and Tyro3 were below the detection limits of the ELISA method., Conclusion: We found the presence of mRNAs encoding Gas6 and the receptor Mer in mouse platelets, but not Axl and Tyro3. Gas6, Axl, and Tyro3 protein levels were below the detection limits of the ELISA. The presence of mRNA is not obvious evidence of protein expression in platelets that have no nucleus or DNA. Further studies are required to clarify the presence of Gas6/TAM receptors in platelets using real-time PCR and more sensitive immunological methods, and future studies on mechanisms will indicate whether the Gas6/TAM pathway is a strategy for treatment of disorders.

The introduction of novel antifungal agents for the treatment of invasive fungal disease in hematological malignancies and also changing treatment strategies have had a great impact in managing affected patients. The medical literature includes some important clinical studies that are being used as evidence for guidelines. The problem with these studies and the guidelines is that they are not very easy to interpret, they include controversial issues, and they are not easy to apply to every patient or country. This paper was designed to critically show the main problems associated with these approaches and provide important information that will help Turkish doctors to adopt them in daily clinical practice.