Myeloproliferative Neoplasm Symptom Assessment Total Symptom Score (MPN-SAF TSS) in Chronic Myeloproliferative Neoplasms, Related with Genetic Burden, and Thrombosis.

Myeloproliferative Neoplasm Symptom Assessment Total Symptom Score (MPN-SAF TSS) is a surrogate marker for symptom evaluation in Chronic Myeloproliferative Neoplasms. There is not enough data to show the relationship between MPN-SAF TSS, JAK2 mutation allele burden, and thrombosis. In this retrospective analysis, we aimed to determine the genetic burdens, clinical features, and relationship with MPN-SAF TSS in MPN patients. One hundred thirty JAK2V617F positive MPN were included in our study. We have calculated MPN-SAF TSS and compared it with clinical features. Patients with higher JAK2V617F mutation allele burden had higher MPN-SAF TSS (p-value 0,008). Patients with thrombosis had higher MPN-SAF TSS scores than patients without thrombosis (p-value 0.003). The mean MPN-SAF TSS was higher in primary myelofibrosis (PMF) patients compared to PV and ET patients. 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, a 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 MPN-SAF TSS in routine clinical practice to enhance patient care and management.

Management of Primary Immune Thrombocytopenia - Turkish Modified Delphi-Based Consensus Statement for Special Considerations.

Introduction: Primary immune thrombocytopenia (ITP) is an acquired disorder of platelets with complex and unclear mechanism of increased immune distruction or impaired production of platelets. While management of ITP is evolving, there is a need for guidance particularly in certain circumstances such as pregnancy, emergency and for patients requiring co-medications. We aimed to determine the tendencies of hematologists in Turkiye on such special conditions. Methods: As a modified Delphi method, Turkish National ITP Working Group founded under Turkish Society of Hematology developed a questionnaire consisting of statements regarding pregnancy, emergency and circumstances regarding co-treatment with antiaggregant or anticoagulants. 107 Hematologists working either in university or state hospitals voted for their agreement or disagreement of the statements for two consequential rounds. Results: Participant hematologists reached an agreement on the starting treatment in pregnant patients with platelets less than 30 x109/L and delivery of either normal or cesarian section to be safely performed above 50 x109/L. For emergency and rescue management of ITP, our panel have agreed against the use of high dose corticosteroids alone, preferred a combination with transfusion or IVIG. For patients who require interventions, platelet counts >50 x109/L were regarded as safe for low risk procedures as well as co-treatment with antiplatelets or anticoagulants. Conclusion: As National ITP study group, we have observed the need to increase the practice guidance in patients with primary ITP requiring additional treatments including invasive interventions, and co-treatments towards coagulation. Decisions on the management of ITP during pregnancy should be individualized. There is a certain 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 the variations in the practices.

Management of Adult Primary Immune Thrombocytopenia: Delphi-Based Consensus Recommendations

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.

Immune Thrombotic Thrombocytopenic Purpura in Elderly Patients: The Roles of PLASMIC and French Scores

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.

Morphologic evaluation of megakaryocytes in immune thrombocytopenia patients older than 80 years.

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 39×109/L and the mean mean platelet volume was 10,33fL. Twelve patients had a target thrombocyte count greater than 30×109/L, while 20 patients had a target platelet count of 75×109/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.

Successful pregnancy and delivery management in a patient with Bernard Soulier Syndrome.

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.

Level of Awareness of Acquired Hemophilia A Among Physicians in Türkiye: A Survey Study

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.

A survey evaluating hematology physicians' perspectives on central nervous system prophylaxis.

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.

Incidence and predisposing factors of infection in patients treated with hypomethylating agents.

OBJECTIVE: Hypomethylating agents may have adverse effects such as cytopenias, cytopenia associated infections and fatality due to infections despite their favorable effects in the treatment of acute myeloid leukemia (AML), myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML). The infection prophylaxis approach is based on expert opinions and real-life experiences. Hence, we aimed to reveal the frequence of infections, predisposing factors of infection and to analyse infection attributable mortality in patients with high-risk MDS, CMML and AML who received hypomethylating agents in our center where routine infection prophylaxis is not applied. MATERIAL-METHOD: 43 adult patients with AML or high-risk MDS or CMML who received HMA ≥ 2 consecutive cycles from January 2014 to December 2020 were enrolled in the study. RESULTS: 43 patients and 173 treatment cycles were analyzed. The median age was 72 years and 61.3 % of patients were males. The distribution of the patients' diagnoses was; AML in 15 patients (34.9 %), high risk MDS in 20 patients (46.5 %), AML with myelodysplasia-related changes in 5 patients (11.6 %) and CMML in 3 patients (7 %). 38 infection events (21.9 %) occurred in 173 treatment cycles. 86.9 % (33 cycles) and 2.6 % (1 cycle) of infected cycles were bacterial and viral infections, respectively and 10.5 % (4 cycles) were bacterial and fungal concurrently. The most common origin of the infection was respiratory system. Hemoglobin count was lower and CRP level was higher at the beginning of the infected cycles significantly (p values were 0.002 and 0.012, respectively). Requirement of red blood cell and platelet transfusions were found to be significantly increased in the infected cycles (p values were 0.000 and 0.001, respectively). While > 4 cycles of treatment and increased platelet count were found to be protective against infection, > 6 points of Charlson Comorbidity Index (CCI) were found to increase the risk of infection. The median survival was 7.8 months in non-infected cycles while 6.83 months in infected cycles. This difference was not statistically significant (p value was 0.077). DISCUSSION: The prevention and management of infections and infection-related deaths in patients treated with HMAs is crucial. Therefore, patients with a lower platelet count or a CCI score of > 6 may be candidates for infection prophylaxis when exposed to HMAs.

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.

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.

Clinical Characteristics and Outcomes of COVID-19 in Turkish Patients with Hematological Malignancies

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.

Could Antinuclear Antibody Positivity Be a Factor Affecting Treatment Response in Immune Thrombocytopenia Patients on Eltrombopag?

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 1st and 6th 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.

Results of multicenter registry for patients with inherited factor VII deficiency in Turkey.

INTRODUCTION: Inherited factor VII (FVII) deficiency (FVIID) is the most common of inherited rare bleeding disorders. Other determinants of clinical severity apart from FVII level (FVIIL) include genetic and environmental factors. We aimed to identify the cut-off FVIILs for general and severe bleedings in patients with FVIID by using an online national registry system including clinical, laboratory, and demographic characteristics of patients. METHODS: Demographic, clinical, and laboratory data of patients with FVIID extracted from the national database, constituted by the Turkish Society of Hematology, were examined. Bleeding phenotypes, general characteristics, and laboratory features were assessed in terms of FVIILs. Bleeding rates and prophylaxis during special procedures/interventions were also recorded. RESULTS: Data from 197 patients showed that 46.2% of patients had FVIIL< 10%. Most bleeds were of mucosal origin (67.7%), and severe bleeds tended to occur in younger patients (median age: 15 (IQR:6-29)). Cut-off FVIILs for all and severe bleeds were 16.5% and 7.5%, respectively. The major reason for long-term prophylaxis was observed as central nervous system bleeding (80%). CONCLUSION: Our data are consistent with most of the published literature in terms of cut-off FVIIL for bleeding, as well as reasons for prophylaxis, showing both an increased severity of bleeding and younger age at diagnosis with decreasing FVIIL. However, in order to offer a classification similar to that in Hemophilia A or B, data of a larger cohort with information about environmental and genetic factors are required.

An unknown chromosomal aberration in a patient with chronic lymphocytic leukemia: Extra isochromosome 4q.

The genetic characterization of chronic lymphocytic leukemia (CLL) has made significant progress over the past few years. Chromosomal abnormalities are detected in up to 80% of patients. Determination of new chromosomal disorders is important in the pathogenesis and treatment facilities. A patient was diagnosed with CLL Stage 2 on 2012 and followed since then by hematology clinic. She was 63 years old. Mature, small lymphocytes, and smudge cell was found in the patient's peripheral blood smear. Bone marrow (BM) biopsy made and hypercellularity showing infiltration of atypical cells with CD5+, CD20+, and CD23+ were determined. Hypoplasia is detected in myeloid/erythroid series, and Stage 2 reticular fibers proliferation were detected. The patient was followed up without medication. While follow-up of patient's white blood cell: 57300, hemoglobin: 5.36, and PLT: 99700 are determined in May 2014. According to the patient's flow results, CD5+, CD23+, and FMC7+ were detected. Mature, small lymphocytes and smudge cell was found in the patient's peripheral blood smear. In ultrasonography imaging, multiple laps were found in the abdomen and multiple neck lymph nodes were detected. The patient BM aspiration was performed in 2014, and hypercellularity was found to contain 54% of atypical lymphocytes in the BM. Fluorescence in situ hybridization (FISH) analysis made two times in 2014. At first, FISH analysis patient's rate of 18% in RB1/13q14.2/13qter revealed a deletion of the gene regions. Patient's FISH result was reported as normal (for RB1/13q14.2/13qter) after 5 months at second analysis. Cytogenetic analysis is made from the patient's BM at the same time. According to the results of karyotyping and FISH, 47, XX, isochromosome 4q (+i4q) is determined. According to literature, extra isochromosome 4q is reported by our case for the first time in CLL. She was diagnosed with Stage 4 CLL and FISH treatment was initiated. Our patient showed disease progression compared to previous results. Hence, we offer that this evidence can be considered regarding triggering the disease's progression or as a result of disease progression i4q was occurred.

The Importance of Targeted Next-Generation Sequencing Usage in Cytogenetically Normal Myeloid Malignancies.

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.

Comparison of Clinical Scoring Systems in the Management of Patients with Microangiopathic Hemolytic Anemia and Thrombocytopenia

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.