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Restless legs syndrome (RLS) is a common but often overlooked cause of sleep disturbance and discomfort during rest. The prevalence of RLS remains unknown in chronic myeloid leukemia (CML). This study explores its frequency, clinical relevance, and impact on quality of life in patients with CML. We consecutively evaluated CML patients who visited our outpatient clinic between January and August 2023. Patients with iron deficiency (ID) and healthy subjects (HS) were also included as controls. Standardized psychometric assessments were administered to CML patients, including IRLSSG Rating Scale, Beck inventories, PSQI, FACIT-Fatigue, and EORTC QLQ-C30/CML24 for evaluating health-related quality of life (HRQoL). Neurological examinations and electromyography were performed in all participants diagnosed with RLS, including controls, to evaluate for secondary causes of peripheral polyneuropathy. A total of 164 CML patients, 22 individuals with ID, and 23 HSs were included. The rates of RLS were 20.1% and 45.5% in patients with CML and ID, respectively. None of the HS had RLS. Compared to non-RLS CML patients, those with RLS exhibited significantly poorer sleep quality (p = 0.016), greater anxiety (p < 0.001), depression (p = 0.005), and fatigue (p < 0.001), alongside elevated symptom burden scores (p < 0.001). Molecular responses and TKI dose modifications were similar between CML patients with and without RLS. Not using ACEi/ARB was associated with a 0.235-fold reduced risk of RLS, and a higher symptom burden score was independently associated with RLS (OR = 1.077). RLS is an underrecognized comorbidity in CML that severely impairs HRQoL, despite no impact on treatment response. Routine screening and targeted symptom management strategies are warranted.

Acquired angioedema due to C1 inhibitor deficiency (AAE-C1INH) is a rare bradykinin-mediated condition that may mimic hereditary angioedema (HAE). Management is largely extrapolated from HAE data. Therefore, retrospective observations in AAE-C1INH are particularly valuable for informing future approaches. This study aimed to evaluate the clinical characteristics, underlying conditions, and treatment outcomes of patients with AAE-C1INH. We conducted a retrospective cohort study of adult patients diagnosed with AAE-C1INH, with a comprehensive review of demographic and clinical features. Among 587 patients with recurrent angioedema, 1.7% had AAE-C1INH. Median onset age was 56.5 years (45.5-66.75), median follow-up was 60.5 months (23.25-66.5), and 20% were female. Clonal hematologic neoplasms were present in 60% of patients and monoclonal gammopathy of undetermined significance in 30%, with angioedema preceding the diagnosis of the underlying condition in 60% of cases. Long-term prophylaxis was required in 50% of patients. Antifibrinolytic agents showed limited efficacy, whereas attenuated androgens were associated with a marked reduction in attack frequency. Rituximab-based therapy effectively controlled angioedema, although relapse occurred during extended follow-up. Complete remission under Bruton's tyrosine kinase (BTK) inhibition was observed despite persistently low complement levels; however, concurrent withdrawal of renin-angiotensin system blockers represents a potential confounder. Complement levels were observed to parallel treatment response in most patients, whereas this association was not observed in the patient receiving a BTK inhibitor. In this rare, well-characterized cohort with extended follow-up, angioedema frequently represented the earliest clinical manifestation of AAE-C1INH, preceding recognition of the underlying disorder. Antifibrinolytic prophylaxis showed limited benefit, whereas attenuated androgens were associated with reduced attack frequency. Furthermore, therapies targeting the underlying lymphoproliferative condition, including rituximab-based regimens and BTK inhibition, were associated with meaningful clinical benefit. These findings support an individualized, etiology-driven management approach and provide practical insights for clinicians managing this rare condition.

Thrombotic thrombocytopenic purpura (TTP) is a rare disease with a mortality rate of over 90% if left untreated. Therapeutic plasma exchange (PEX) is the mainstay of treatment of acquired TTP (aTTP), and with the introduction of PEX, the mortality rate declined dramatically below 20%. Although PEX together with corticosteroids are the backbone of the upfront management of patients with aTTP with successful outcomes, patients may remain refractory and/or relapse following an initial response to this treatment. There are some therapeutic options, which can be used among these patients, helping in improving outcomes of aTTP. Caplacizumab (formerly ALX-0081 or ALX-0681) is a humanized single-variable domain immunoglobulin that recognizes the human von Willebrand factor (vWF) A1 domain and inhibits the vWF-platelet glycoprotein 1b-alpha (GP1b-α) interaction. The drug was first developed for the prevention of thrombosis in high-risk patients with acute coronary syndrome undergoing percutaneous coronary intervention; however, drug development for this indication has been discontinued. Recently, caplacizumab received its first approval following Phase II TITAN and Phase III HERCULES trials in the European Union (EU) for the treatment of acute episode of aTTP in adult patients, in addition to PEX and immunosuppression. This review focuses on the use of caplacizumab as an emerging treatment option in patients with aTTP.

BackgroundNeutrophil extracellular trap (NET) formation has emerged as a key driver of thrombosis in myeloproliferative neoplasms (MPNs). Its role in congenital bleeding disorders, however, remains unexplored.ObjectivesTo investigate circulating citrullinated histone H3 (cit-H3), a marker of NETosis, in thrombosis-prone MPNs and bleeding-prone severe hemophilia A.MethodsIn a cross-sectional study, plasma cit-H3 was quantified by ELISA in patients with JAK2-mutated polycythemia vera or essential thrombocythemia, patients with severe hemophilia A, and matched healthy controls. Clinical and laboratory data were analyzed for associations with cit-H3 levels.ResultsEighty-nine participants were included: 26 with myeloproliferative neoplasms (MPNs), 31 with severe hemophilia A, and 32 healthy controls. Demographic characteristics were comparable across groups, though comorbidities were more frequent in MPNs. Laboratory analyses confirmed expected disease-specific differences, including elevated leukocyte, neutrophil, and platelet counts in MPNs and prolonged activated partial thromboplastin time in hemophilia A. Circulating citrullinated histone H3 (cit-H3) levels differed significantly among groups (p < 0.001), being lowest in controls, intermediate in MPNs, and highest in hemophilia A. Within disease groups, cit-H3 levels were unaffected by clinical variables such as MPN subtype, aspirin use, phlebotomy history, or factor replacement regimen.ConclusionsElevated circulating cit-H3 levels, suggestive of increased NETosis activity, were observed in both thrombosis-prone MPNs and bleeding-prone hemophilia A. These exploratory findings suggest a possible association between NET formation and thromboinflammatory processes across distinct hemostatic disorders.

Acquired hemophilia A (AHA) is a rare but potentially life-threatening bleeding disorder. This single-center retrospective study aimed to assess clinical features, treatment strategies, and prognostic indicators in adult AHA patients. Eleven patients diagnosed between 2008 and 2024 were reviewed. Clinical data, laboratory findings, treatments, and outcomes were analyzed. Survival estimates and prognostic factors were evaluated using Kaplan-Meier and univariate analyses. Median age was 41 years; 54.5% of the patients were female. Pregnancy-associated AHA (36.4%) had excellent outcomes with steroid monotherapy and no relapse. Idiopathic and autoimmune cases required combination therapy and had higher relapse rates. The median follow-up duration was 27 months. All patients achieved remission (median response time: 62 days), though 36.4% relapsed. High inhibitor titer (>20 Bethesda unit) predicted delayed response (p=0.038); male sex and major bleeding were linked to shorter relapse-free survival. Baseline inhibitor burden and disease etiology influence AHA prognosis. Tailored therapy and multicenter validation are warranted to refine management strategies.

Patients with large B-cell lymphoma (LBCL) who are relapsed/refractory (R/R) after frontline therapy have traditionally experienced highly unfavorable outcomes. The development of T-cell redirecting therapies is rapidly changing that outlook, but costs and infrastructural challenges limit access to these innovative therapies. This study was conducted to document the shortcomings of management in the absence of regular access to T-cell redirecting therapies in a contemporary patient population and define the subgroups with the most urgent need for accessing innovative treatments. The second-line management strategies and outcomes of a large real-world LBCL cohort from Türkiye were retrospectively analyzed with the participation of 9 centers from 4 different geographical regions. Despite the contemporary nature of the treatment strategies (2012-2024), there was no regular access to novel agents. The median progression-free survival after the first progression (PFS-2) was 6.9 months. Fewer than one-fourth of all patients (24.3%) received transplantation following a response to second-line therapy, constituting the only subgroup to benefit from standard care (2-year PFS-2: 67.8%). The remaining 295 patients (75.7% of the cohort) had median survival of 6.1 months and 2-year PFS-2 of 10.3%. Progression within a year from diagnosis, non-curative intent at the second line of therapy, and failure of curative second-line therapy were key adverse features for a dismal prognosis, with median survival durations of 8.8, 2, and 7.4 months, respectively. The current therapeutic strategy of intensive chemoimmunotherapy followed by autologous transplantation yields a reasonable chance of survival for only one-fifth of patients. The findings of this study emphasize the urgent need for expanding access to T-cell redirecting approaches in R/R LBCL for early progressors, transplant-ineligible cases, and patients who fail intensive second-line regimens.

Extramedullary disease (EMD) is an aggressive manifestation of multiple myeloma (MM) and is categorized into two distinct types: extramedullary-bone-related (EM-B) and extramedullary-extraosseous (EM-E). We aimed to investigate differences in the characteristics of disease and outcomes between these two types. This single-center, retrospective study included 132 patients with EMD who were diagnosed with MM between January 2010 and January 2020. Patients were divided into EM-B (n = 93) and EM-E (n = 39), and clinicopathological features and survival outcomes were analyzed. EMD was observed in 98 (74.2%) patients at initial diagnosis and in 34 (25.8%) during a relapse. EM-E was significantly associated with ≥ 2 involved sites, high bone marrow plasma cell percentage, high LDH and beta-2 microglobulin levels, anemia, and high-risk fluorescence in situ hybridization abnormalities compared to EM-B. Patients with EM-E had significantly shorter progression-free survival and overall survival than those with EM-B. Anemia, hypercalcemia, high LDH, EMD at relapse, ≥ 2 involved sites, and not receiving autologous stem cell transplantation were independent poor risk factors for survival. In conclusion, EMD is a heterogeneous entity, and this study demonstrated that patients with EM-E presented with different clinicopathological characteristics and had worse survival compared to those with EM-B.

Introduction: Coronavirus disease 2019 (COVID-19) is the biggest health challenge of recent times. Studies so far reveal that vaccination is the only way to prevent this pandemic. There may be factors that decrease or increase vaccine effectiveness. In multiple sclerosis (MS), some of these factors may cause changes in the effectiveness of the vaccine, depending on the nature of the disease and disease-modifying treatments (DMT). In this study, we aimed to investigate the relationship between antibody titer and smoking in non-treated and DMT-treated MS patients who received inactivated vaccine (Sinovac) and messenger RNA BNT162b2 (BioNTech) mRNA vaccines. Method: Vaccine antibody responses were measured between 4-12 weeks after two doses of inactivated vaccine and mRNA vaccines. Patients were separated into 6 groups as: patients with MS without treatment PwMS w/o T, ocrelizumab, fingolimod, interferons (interferon beta-1a and interferon beta-1b), dimethyl fumarate, and teriflunomide. Antibody titers of smokers and non-smokers were compared for both vaccines and for each group. Results: The study included 798 patients. In the mRNA vaccine group, smokers (n=148; 2982[+ or -]326 AU/mL) had lower antibody titers compared to the non-smokers (n=244; 5903[+ or -]545 AU/mL) in total (p=0.020). In the inactivated vaccine group, no significant difference was detected between smokers (n=136; 383[+ or -]51 AU/mL) and non-smokers (n=270; 388[+ or -]49 AU/mL) in total (p=0.149). In both vaccine groups, patients receiving ocrelizumab and fingolimod had lower antibody titers than those receiving other DMTs or PwMS w/o T. In untreated MS patients, antibody levels in smokers were lower than in non-smokers in the mRNA vaccine group. No difference was found between antibody levels of smokers and non-smokers in any of the inactivated vaccine groups. Conclusion: Ocrelizumab and fingolimod have lower antibody levels than PwMS w/o T or other DMTs in both mRNA and inactivated vaccine groups. Smoking decreases antibody levels in the mRNA vaccine group, while it has no effect in the inactivated vaccine group. Keywords: COVID-19, disease modifying therapy, multiple sclerosis, smoking, vaccine

Redditux (RED), as a biosimilar rituximab, was approved in Turkey for all indications of the original Mabthera (MAB) in March 2018. The aim of our study was to evaluate the efficacy and safety of RED in de novo diffuse large B-cell lymphoma. Fifty-one patients received RED combined with the CHOP regimen. The median follow-up was 31 months. The historical control group included 219 patients treated with the MAB-CHOP regimen and the median follow-up time was 38 months. We compared the response rates and survival outcomes of these RED-CHOP and MAB-CHOP cohorts. In the RED cohort, the overall response rate (ORR) at the end of the treatment protocol was 86%, with 37 (72.5%) cases of complete response (CR) and 7 (13.5%) cases of partial response (PR). In the historical MAB cohort, the ORR was 84%, with CR and PR rates of 82% and 2%, respectively. The 24-month progression-free survival (PFS) rates were 73.76% (95% confidence interval [CI]: 0.59-0.84) and 85.2% (95% CI: 0.79-0.90) for the RED and MAB cohorts, respectively (p=0.0106). The 24-month overall survival rates were 78.4% (95% CI: 0.64-0.87) and 81.4% (95% CI: 0.75-0.86) for the RED and MAB cohorts, respectively (p=0.7461). For patients with high revised International Prognostic Index scores, 24-month PFS was 45.5% (95% CI: 0.17-0.71) and 63% (95% CI: 0.37-0.80) for the RED and MAB cohorts, respectively (p=0.0711). In the RED cohort, central nervous system (CNS) relapse was significantly increased compared to the MAB cohort (10% vs. 1.83%, p=0.004). Among the RED cohort, bone involvement at the time of diagnosis was a risk factor for CNS relapse (p=0.028). Thirteen patients died in follow-up. There were no serious adverse events causing the cessation of the drugs. RED has an ORR similar to that of MAB. However, PFS rates were worse in the RED cohort. Additionally, CNS relapse ratio was a major concern for our RED cohort. Large prospective controlled studies and real-life data with longer follow-up are needed to document the non-inferiority of RED compared to MAB.

In this study, we retrospectively analyzed the clinical outcome, treatment responses, infectious complications, and survival rates of 71 hairy cell leukemia (HCL) cases. Sixty-seven patients received a first-line treatment and 2-chlorodeoxyadenosine (cladribine-2-CdA) was administered in 31 cases, 19 patients received interferon-alpha (INF-α), splenectomy was performed in 16 cases, and rituximab was used in one. Although the highest overall response rate (ORR) was observed in patients receiving 2-CdA upfront, ORRs were comparable in the 2-CdA, INF-α, and splenectomy subgroups. Relapse rates were significantly lower in patients who received first-line 2-CdA. The progression-free survival (PFS) rate with 2-CdA was significantly higher than in patients with INF-α and splenectomy, but we found similar overall survival rates with all three upfront treatment modalities. Infections including tuberculosis were a major problem. Although purine analogues have improved the ORRs and PFS, there is still much progress to make with regard to overall survival and relapsed/refractory disease in patients with HCL.