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.

Evaluation of New Generation Sequencing (NGS)-Based Somatic Gene Variations and Real-Time Polymerase Chain Reaction (PCR)-Based Gene Fusions in Elderly and Young Acute Leukemia Patients: A Retrospective View.

Malignant diseases occurring in elderly patients follow a different course from younger patients and show different genetic structures. Therefore, in this retrospective study, the somatic gene variant profile and fusion gene profiles of elderly and young acute leukemia patients were determined to draw attention to the existing genetic difference, and the results were compared. In this study, the records of 204 acute leukemia patients aged 18+ who were referred to the Molecular Pathology Laboratory from the Hematology Clinic between 2018 and 2022 were reviewed retrospectively. Fusion gene detection in patients was performed with the HemaVision®-28Q Panel. The NGS Myeloid Neoplasms Panel was conducted using the MiniSEQ NGS platform according to the manufacturer's protocol. When all cases are evaluated together, the most frequently diagnosed acute leukemia is acute myeloid leukemia (85.8%). Both groups had a similar fusion gene profile; however, the fusion burden was higher in the elderly group. When the groups were evaluated in terms of somatic gene variations, there were differences between the groups, and the variation load was higher in the elderly group. Considering the different somatic gene variation profiles, it is understood that the genetic structure of tumor cells is different in elderly patients compared to young cases.

The relationship between peripheral T follicular helper cells and disease severity in systemic sclerosis.

We aimed to investigate the association between follicular T helper cells (Tfh) and disease severity in systemic sclerosis (SSc), a chronic connective tissue disease characterized by progressive fibrosis. While Tfh cells have been extensively studied in other autoimmune diseases, their role in SSc remains poorly understood. A cohort of 50 SSc patients, diagnosed based on the ACR/EULAR 2013 classification criteria, was included in the study. Patient data, including demographic information, comorbidities, treatment history and organ involvement, were collected. Disease severity was assessed using the modified Rodnan skin score and Medsger disease severity index. Statistical analyses were performed, considering a p value of < 0.05 as statistically significant. 38% had SSc with limited skin involvement, while 62% had SSc with extensive skin involvement. However, there were no statistically significant differences observed in the levels of CD4+ CXCR5+ , CD4+ ICOS+ , CD4+ CD40L+ and CD4+ PD+ lymphocytes between the two groups. Notably, SSc patients with Raynaud's phenomenon, digital ulcer and lung involvement exhibited higher levels of CD4+ CXCR5+ lymphocytes compared to those without these manifestations. Furthermore, a significant positive correlation was observed between CD4+ CXCR5+ lymphocyte levels and the severity of lung disease according to the Medsger disease severity index. Based on these findings, we conclude that elevated levels of Tfh cells are associated with lung involvement in SSc and there is a significant correlation between Tfh cell levels and the severity of lung disease. These observations suggest a potential role for Tfh cells in the pathogenesis of lung involvement in SSc and may guide the development of targeted therapies for this aspect of the disease.

Sustained response off-treatment in eltrombopag-treated adult patients with ITP who are refractory or relapsed after first-line steroids: Primary, final, and ad-hoc analyses of the Phase II TAPER trial.

Immune thrombocytopenia (ITP) is characterized by reduced platelet count due to increased destruction and is categorized according to the time following diagnosis (newly diagnosed, persistent, chronic). First-line corticosteroid therapy is associated with transient response, high relapse rates, and considerable toxicity. TAPER (NCT03524612) is a Phase II, prospective, single-arm trial investigating whether eltrombopag can induce a sustained response off-treatment (SRoT) in adult patients with ITP after first-line corticosteroid failure. This study defines SRoT as an off-treatment period wherein platelet count remains above 30 × 109 /L in the absence of bleeding or rescue therapy. The primary endpoint was the proportion of patients who achieved SRoT until Month 12, which was 30.5% (n = 32/105; p < .0001 testing hypothesis H1: proportion >15%) following eltrombopag tapering and discontinuation, and median SRoT duration was ~8 months until Month 12. Median platelet count increased within 1 month of treatment and remained elevated until Month 12. Quality of life improved within 3 months and was maintained. Headache (21%) was the most common adverse event. None of the 4 deaths reported were considered treatment-related. In summary, ~one-third of patients achieved SRoT until Month 12 following eltrombopag tapering and discontinuation. An ad-hoc early-use analysis, stratified by ITP duration at baseline, assessed initial hematologic responses and safety. Results suggest that eltrombopag has similar efficacy in newly diagnosed and later stages of ITP. In follow-up until Month 24, a median SRoT duration of ~22 months was observed (n = 20). The safety profile was comparable across analyses and ITP duration groups and aligned with its well-established safety profile.

Glofitamab in relapsed/refractory diffuse large B-cell lymphoma: Real-world data.

Glofitamab is a CD3xCD20 bi-specific antibody with two fragments directed to the CD20 antigen and a single CD3-binding fragment. Encouraging response and survival rates were recently reported in a pivotal phase II expansion trial conducted in patients with relapsed/refractory (R/R) B-cell lymphoma. However, the real-world data of patients of all ages with no strict selection criteria are still lacking. Herein, this retrospective study aimed to evaluate the outcomes of diffuse large B-cell lymphoma (DLBCL) patients who received glofitamab via compassionate use in Turkey. Forty-three patients from 20 centers who received at least one dose of the treatment were included in this study. The median age was 54 years. The median number of previous therapies was 4, and 23 patients were refractory to first-line treatment. Twenty patients had previously undergone autologous stem cell transplantation. The median follow-up time was 5.7 months. In efficacy-evaluable patients, 21% and 16% of them achieved complete response and partial response, respectively. The median response duration was 6.3 months. The median progression-free survival (PFS) and overall survival (OS) was 3.3 and 8.8 months, respectively. None of the treatment-responsive patients progressed during the study period, and their estimated 1-year PFS and OS rate was 83%. The most frequently reported toxicity was hematological toxicity. Sixteen patients survived, while 27 died at the time of the analysis. The most common cause of death was disease progression. One patient died of cytokine release syndrome during the first cycle after receiving the first dose of glofitamab. Meanwhile, two patients died due to glofitamab-related febrile neutropenia. This is the largest real-world study on the effectiveness and toxicity of glofitamab treatment in R/R DLBCL patients. The median OS of 9 months seems promising in this heavily pretreated group. The toxicity related mortality rates were the primary concerns in this study.

Acquired Hemophilia A In Adults: A Multicenter Study from Turkey.

Acquired hemophilia A (AHA) is a rare disease caused by autoantibodies inhibiting factor VIII (FVIII) activity. Although the conditionis usually idiopathic, there may be other underlying diseases. Treatment consists of two steps: treatment of acute bleeding and immunosuppression. In this multicenter study, we aimed to demonstrate the clinical characteristics, management details, and survival of AHA patients in Turkey. Data was collected from eleven centers in Turkey. aPTT, FVIII, FVIII inhibitor, and hemoglobin (HB) levels, mixing test results, and demographics at diagnosis, treatment information, adverse events, bleeding episodes during follow-up, relapses, and outcome were analyzed. Twenty-nine patients were analyzed (58.6% female). No underlying disorder could be detected in 14 patients. The most prevalent etiologies were pregnancy, malignancy and infections. The median FVIII activity and FVIII inhibitor titer at diagnosis were 0.7% (0.0-29.4%) and 32.6 BU (0.6-135.6 BU) respectively. Bleeding was severe in 44.8% of patients. The HB value was significantly lower in patients with severe bleeding. Most of the patients (n = 25, 86.2%) had only one bleeding episode without relapse, three patients (10.3%) had two bleeding episodes, and one patient had more than three bleedings. 21 (75%) patients received hemostatic therapy. The use of recombinant FVIIa was slightly higher than activated prothrombin complex concentrate (15 versus 10 patients). Immunosuppressive treatment was initiated in 26 (93%) patients. Regimens containing steroid, cyclophosphamide, and rituximab in different combinations were the most preferred. The median follow-up period was 13 months (2-156 months). Median overall survival was 154.97 months. Four and six-year survival were 90.9 ± 0.8% and 77.9 ± 14.1% respectively. This is a unique study that investigated the demographic characteristics, treatment approaches, and patient survival of AHA in Turkey.

Eltrombopag in patients with chronic immune thrombocytopenia in Asia-Pacific, the Middle East, and Turkey: final analysis of CITE.

CITE was a prospective, noninterventional study in adult patients with chronic immune thrombocytopenia treated with eltrombopag under routine clinical care in Asia-Pacific, the Middle East, and Turkey. Data to assess eltrombopag usage, compliance, and outcomes were collected from May 2017 to December 2020. Platelet response was defined as platelet count ≥50 × 103/µL in the absence of rescue medications and splenectomy. Quality of life was evaluated using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) questionnaire. Noncompliance was defined as the number of missed doses and number of days where the patient did not follow food instructions. A total of 231 patients were enrolled; the median (range) duration of eltrombopag treatment was 484.5 (1-642) days. Compliance to prescribed eltrombopag dose since the previous routine visit was high at ≥96.0%. Baseline median platelet count was 19.0 × 103/µL, which increased to ≥50 × 103/µL at month 2 and mostly fluctuated between 70 × 103/µL and 100 × 103/µL thereafter. The median time to first platelet response was 1.05 (95% confidence interval: 0.92-1.28) months, and the median (interquartile range) maximum duration of platelet response was 193 (57-456) days. FACIT-F scores improved from a mean (standard deviation) 34.4 (12.1) at baseline to 38.5 (9.1) at month 18. Adverse events occurred in 50.9% of patients (n = 116), the most common being upper respiratory tract infection (8.3%) and headache (6.6%). These findings confirmed the effectiveness of eltrombopag treatment in routine practice and reassured that real-world compliance to eltrombopag-prescribed doses and dietary instructions in Asia-Pacific, the Middle East, and Turkey were in line with current recommendations.

The evaluation of gene mutation profiles by next-generation sequencing in diffuse large B-cell lymphoma.

OBJECTIVE: Diffuse large B cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma. Although it is a clinically and biologically heterogeneous disease, it is usually treated with R-CHOP chemotherapy. Here, we aimed to investigate gene expression frequency with next-generation sequencing (NGS) and the relation of gene mutations with remission and relapse status in patients with DLBCLs. MATERIALS AND METHODS: We investigated gene mutation profiles by NGS in patients with DLBCL-NOS and analyzed the correlation between gene mutations and response and relapse rates and other clinical indices. RESULTS: Twenty-eight of forty patients were evaluated. The most commonly mutated genes were ANKRD, BRCA1, BRCA2, EZH2, KMTC2, MYC, MYD88, NF1, NOTCH1, PMS2, PTEN, and WRN. The relapse rate was found higher in DLBCL patients with ANKRD26, BRCA2, MYD88, and NOTCH1 mutations. Also, remission duration was found shorter in patients with ANKRD26, BRCA2, and MYD88 mutations. CONCLUSIONS: Our study demonstrates that the presence of some genetic mutations is effective on prognosis in patients with DLBCL. NGS-based evaluation of DLBCL treatment can be used in the future.

Immature platelet fraction in rheumatoid arthritis with interstitial lung disease.

BACKGROUND: Platelets have an effect on the hemostatic defense of the lung. Immature platelet fractions (iPF) reflects the number of young platelets containing ribonucleic acid in the circulation and real-time production. Information about their roles in rheumatic diseases is limited and there are no studies on iPF in RA with interstitial lung disease (ILD). Our aim is to investigate the association between the iPF level and occurrence of ILD in RA and the correlation of iPF with disease activity in general or only in RA with ILD. METHODS: The study included 50 RA patients without ILD, 33 RA patients with ILD, and 30 healthy controls. Demographic data, Disease Activity Score 28 (DAS28), autoantibodies, and iPF were evaluated. ILD was diagnosed by using high-resolution computed tomography with clinical findings and chest X-ray. The samples were analyzed for complete blood count with platelet indices included, on Mindray BC-6800 hematology analyzer, Hamburg, Germany. RESULTS: iPF levels were higher in RA patients with ILD compared to healthy controls and RA patients without ILD. A weakly positive correlation between DAS28 with iPF was found in all RA patients. iPF levels were found as 2.85 to detect ILD with 66.7% sensitivity and 65% specificity. CONCLUSIONS: Our results showed that the iPF was detected higher in RA with ILD compared to RA without ILD. iPF, a routine cheap and easy test during hemogram, can provide important information in terms of disease activity and lung involvement in RA.

Immature platelet fraction in rheumatoid arthritis with interstitial lung disease / Fracción plaqueta inmadura en artritis reumatoide con enfermedad pulmonar intersticial

Background: Platelets have an effect on the hemostatic defense of the lung. Immature platelet fractions (iPF) reflects the number of young platelets containing ribonucleic acid in the circulation and real-time production. Information about their roles in rheumatic diseases is limited and there are no studies on iPF in RA with interstitial lung disease (ILD). Our aim is to investigate the association between the iPF level and occurrence of ILD in RA and the correlation of iPF with disease activity in general or only in RA with ILD. Methods: the study included 50 RA patients without ILD, 33 RA patients with ILD, and 30 healthy controls. Demographic data, Disease Activity Score 28 (DAS28), autoantibodies, and iPF were evaluated. ILD was diagnosed by using high-resolution computed tomography with clinical findings and chest X-ray. The samples were analyzed for complete blood count with platelet indices included, on Mindray BC-6800 hematology analyzer, Hamburg, Germany. Results: iPF levels were higher in RA patients with ILD compared to healthy controls and RA patients without ILD. A weakly positive correlation between DAS28 with iPF was found in all RA patients. iPF levels were found as 2.85 to detect ILD with 66.7% sensitivity and 65% specificity. Conclusions: Our results showed that the iPF was detected higher in RA with ILD compared to RA without ILD. iPF, a routine cheap and easy test during hemogram, can provide important information in terms of disease activity and lung involvement in RA.(AU)

Antecedentes: Las plaquetas tienen un efecto sobre la defensa hemostática del pulmón. Las fracciones de plaquetas inmaduras (FPi) reflejan el número de plaquetas jóvenes que contienen ácido ribonucleico en la circulación y la producción en tiempo real. La información sobre su papel en las enfermedades reumáticas es limitada y no existen estudios sobre la FPi en la AR con enfermedad pulmonar intersticial (EPI). Nuestro objetivo es investigar la asociación entre el nivel de FPi y la aparición de EPI en la AR y la correlación de la FPi con la actividad de la enfermedad en general o solo en la AR con EPI. Métodos: El estudio incluyó a 50 pacientes con AR sin EPI, 33 pacientes con AR con EPI y 30 controles sanos. Se evaluaron los datos demográficos, la puntuación de actividad de la enfermedad 28 (DAS28), los autoanticuerpos y la FPi. La EPI se diagnosticó mediante tomografía computarizada de alta resolución, con hallazgos clínicos y radiografía de tórax. Las muestras fueron analizadas para un recuento sanguíneo completo con índices de plaquetas incluidos, en el analizador de hematología Mindray BC-6800, Hamburgo, Alemania. Resultados: Los niveles de FPi fueron más altos en los pacientes con AR con EPI en comparación con los controles sanos y los pacientes con AR sin EPI. Se encontró una correlación débilmente positiva entre DAS28 y FPi en todos los pacientes con AR. Se encontró que los niveles de FPi eran de 2,85 para detectar ILD con una sensibilidad del 66,7% y una especificidad del 65%. Conclusiones: Nuestros resultados mostraron que la FPi se detectó más en AR con EPI en comparación con AR sin EPI. La FPi, una prueba de rutina barata y fácil durante el hemograma, puede proporcionar información importante en términos de la actividad de la enfermedad y la afectación pulmonar en la AR.(AU)

The relationship between red cell distribution width and prognostic scores in myelodysplastic syndrome.

INTRODUCTION: The myelodysplastic syndrome (MDS) represents a group of hematopoietic neoplasms that is characterized by clonal hematopoiesis, cytopenia and abnormal cellular maturation. Red cell distribution width (RDW) refers to the variation degree of erythrocyte size and it is a reflection of anisocytosis. Higher values have been linked to adverse outcomes, such as increased mortality, vascular events, kidney and liver disease and demonstrated to harbor poor prognosis in solid and hematological malignancies. The RDW value can be used as a contributing parameter for MDS diagnosis, as well as its prognosis. In this study, we essentially aimed to demonstrate the correlation between the RDW and MDS prognostic indexes. MATERIALS AND METHODS: Ninety-four MDS patients at the Aydin Adnan Menderes University Hematology Division were included in the study. The correlations between the RDW and laboratory values (either lactate dehydrogenase, albumin, globulin or ferritin) and the RDW prognostic scoring indexes (IPSS, WPSS, IPSS-R and LR-PSS) were investigated. The PASW for Windows, version 21.0 (SPSS Inc., Chicago, IL, USA), was used for statistical assessment. A p-value below 0.05 was the cut-off for the statistical significance. RESULTS: The mean age of all the patients was 73 ±â€¯10 years. Patients were observed for 41.88 ±â€¯25 months. The mean RDW value for all cases was 15.5 ±â€¯2.39. We found a statistically significant difference of survival between RDW values below and above 15.5% (p = 0.016). A significant difference was also observed according to the prognostic scoring indexes (see below). CONCLUSION: An increase in RDW is probably related to dysplasia in the MDS and this constitutes a possible explanation for the poor outcome. Prognostic indexes might incorporate the RDW as a parameter in the future.

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.

COVID-19-associated Evans syndrome: A case report and review of the literature.

Evans syndrome is a rare condition characterized by simultaneous or sequential development of autoimmune hemolytic anemia and immune thrombocytopenia (and/or immune neutropenia). Coronavirus disease 2019 (COVID-19) may cause various hematologic conditions, such as coagulation abnormalities (e.g., bleeding or thrombosis) or cell count alterations (e.g., lymphopenia and neutrophilia). COVID-19 may also induce Evans syndrome via immune mechanisms. Here, we describe the case of a patient developing Evans syndrome shortly after COVID-19 infection. Immune thrombocytopenia and warm-type autoimmune hemolytic anemia developed simultaneously, and intravenous immunoglobulin and methylprednisolone were initially administered. Additionally, we intend to review all COVID-19-induced Evans syndrome cases currently present in the literature and emphasize the differences as well as the similarities regarding patient characteristics, relationship to COVID-19 infection, and treatment approach. Since autoimmune cytopenias are frequent in COVID-19 patients, clinicians should pay particular attention to profound and abrupt-onset cytopenias. In these circumstances, hemolysis markers such as lactate dehydrogenase, haptoglobulin, Coombs tests, etc. should be investigated, and the possibility of Evans syndrome should always be considered to ensure prompt and appropriate treatment. These factors are essential to ensure hematologic recovery and prevent complications such as thrombosis.