OBJECTIVES: Eosinophilia is a common laboratory finding that frequently prompts referral for hematologic evaluation, yet the clinical utility of these consultations remains poorly characterized. This study aims to refine...OBJECTIVES: Eosinophilia is a common laboratory finding that frequently prompts referral for hematologic evaluation, yet the clinical utility of these consultations remains poorly characterized. This study aims to refine stratification for eosinophilia and characterize the spectrum of associated diagnoses. METHODS: We conducted a retrospective study of patients referred to hematology at the Oregon Health & Science University between 2015 and 2025 with confirmed eosinophilia based on an absolute eosinophil count (AEC) ≥ 0.5 × 10/L. RESULTS: A total of 142 patients were evaluated for eosinophilia during the study period. The etiology of eosinophilia was deemed idiopathic in 44.8% (n = 64) of patients. Hypereosinophilic syndrome was diagnosed in 20.3% of patients (n = 29) and analyzed as a clinical syndrome, with most cases classified as HES not otherwise specified. The identifiable secondary causes of eosinophilia included asthma (9.8%), parasitic infection (7.7%), autoimmune disease (4.9%), and drug reactions (4.9%). Eosinophilia-specific therapies were administered in 22.5% (n = 32) of patients. Receiver operating characteristic (ROC) analysis demonstrated that peak AEC was a strong predictor of clinically meaningful eosinophilia, defined as a diagnosis of HES or need for eosinophilia-specific treatment, with an area under the curve of 0.83. An AEC threshold of 1.5 × 10/L yielded a high sensitivity of 97% for clinically meaningful eosinophilia. CONCLUSIONS: These findings support considering a threshold of 1.5 × 10/L or higher for hematology referral, especially in low-risk and asymptomatic patients, though external validation is needed.
Covalent Bruton tyrosine kinase inhibitor (cBTKi)-based regimens have redefined therapy for chronic lymphocytic leukemia (CLL). However, continuous treatment with BTKis can select for therapy resistance, typically associ...Covalent Bruton tyrosine kinase inhibitor (cBTKi)-based regimens have redefined therapy for chronic lymphocytic leukemia (CLL). However, continuous treatment with BTKis can select for therapy resistance, typically associated with BTK C481 mutations and fosfolipasi C gamma 2 (PLCγ2) activation. In addition, continuous BTKi therapy poses challenges for treatment interruptions and dose modifications, with implications for clinical outcomes. Pirtobrutinib, a highly selective, reversible (noncovalent) BTKi, inhibits BTK independently of C481 and maintains sustained target engagement. In patients with cBTKi-pretreated relapsed/refractory (R/R) CLL, the BRUIN-CLL-321 trial demonstrated improved progression-free survival (PFS) and time to next treatment (TTNT) compared with idelalisib/rituximab or bendamustine/rituximab, accompanied by a favorable tolerability profile. Data from randomized phase III BRUIN-CLL-313 and BRUIN-CLL-314 trials demonstrate the superiority of pirtobrutinib over chemoimmunotherapy in untreated patients and non-inferiority to ibrutinib in untreated patients or in patients with R/R disease who had no prior exposure to cBTKis. These data are not sufficient to justify a change in clinical practice; however, they lay the groundwork for a potential future repositioning of pirtobrutinib from the treatment of R/R CLL to earlier lines of therapy. In this review, we address a range of current and prospective aspects of pirtobrutinib-based therapies: (1) the strengths and limitations of the trial datasets; (2) the biological rationale for frontline noncovalent BTK inhibition; (3) sequencing trade-offs; and (4) prospective scenarios, including combination strategies and time-limited regimens.
OBJECTIVE: Laparoscopic adrenalectomy is standard in adults, but evidence in children remains limited. This study describes a standardised transperitoneal laparoscopic adrenal compartment resection technique and evaluate...OBJECTIVE: Laparoscopic adrenalectomy is standard in adults, but evidence in children remains limited. This study describes a standardised transperitoneal laparoscopic adrenal compartment resection technique and evaluates its safety, reproducibility and outcomes. METHODS: All paediatric patients undergoing transperitoneal laparoscopic adrenalectomy at our centre from 2022 to 2025 were retrospectively reviewed. Clinical and intraoperative data were collected. Procedures were standardised with lateral positioning, three to four subcostal trocars and dissection along embryological avascular planes, avoiding direct gland manipulation. RESULTS: Eleven patients were included, median age 4.3 years. Nine had neuroblastic tumours and two had adrenocortical tumours. Mean tumour volume was 197 cm, mean diameter 39.7 mm. Conversion to open surgery occurred in two IDRF-positive neuroblastomas (18%) due to bleeding and adherence to renal vein. Mean operative time was 157 min; mean hospitalisation 5.2 days. No postoperative complications occurred. All patients had complete macroscopic resection; four (36.4%) showed microscopic margin infiltration. No local recurrences; one high-risk neuroblastoma progressed with metastases. CONCLUSIONS: Standardised laparoscopic adrenal compartment resection is safe and reproducible in selected paediatric patients, feasible even in IDRF-positive tumours. Exclusive dissection along avascular embryological planes ensures oncological radicality, maintaining minimally invasive benefits.
BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment for paroxysmal nocturnal hemoglobinuria (PNH). Post-transplant cyclophosphamide (PTCy) has improved HSCT safety in othe...BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment for paroxysmal nocturnal hemoglobinuria (PNH). Post-transplant cyclophosphamide (PTCy) has improved HSCT safety in other diseases, but its use in PNH is poorly characterized. METHODS: In this retrospective study, we analyzed outcomes of 19 patients with large PNH clones (≥ 50%) undergoing HSCT (2016-2025). Seven patients received a PTCy-based platform (fludarabine-busulfan-cyclophosphamide conditioning with PTCy-based graft-versus-host disease [GvHD] prophylaxis), whereas 12 received conventional prophylaxis. RESULTS: Patients' median age was 32 years; 68% had PNH with bone marrow failure. After a median follow-up of 1349 days, overall and event-free survival rates were 100% and 94.4%, respectively. All patients engrafted rapidly with full donor chimerism. No cases of chronic or grades II-IV acute GvHD occurred in the PTCy group (0/7); however, chronic GvHD and grades II-IV acute GvHD occurred in 15.8% and 10.5% of patients in the conventional group, respectively. No transplant-related mortality or thrombotic events occurred. CONCLUSION: This study, representing the largest reported experience with PTCy-based HSCT for PNH, suggests that this platform is feasible and associated with excellent survival and a promising GvHD profile. These preliminary findings support further investigation of PTCy in transplant strategies for PNH.
Mancuso K, Masci S, Talarico M
… +16 more, Vitale A, Barbato S, Solli V, Puppi M, Rizzello I, Pantani L, Tacchetti P, Iezza M, Restuccia R, Sacchetti I, Manzato E, Ghibellini S, Armuzzi S, Taurisano B, Cavo M, Zamagni E
Eur J Haematol
· 2026 Jun · PMID 41813608
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Modern therapies have clearly marked the history of multiple myeloma (MM), leading to undisputed advantages in terms of sustained responses and prolonged survival, while progressively improving patients' quality of life....Modern therapies have clearly marked the history of multiple myeloma (MM), leading to undisputed advantages in terms of sustained responses and prolonged survival, while progressively improving patients' quality of life. Nonetheless, disease recurrence and resistance to available therapies underscore the importance of identifying additional treatment options, especially in hard-to-treat patients, or when access to cutting-edge immunotherapies is limited. Melflufen (melphalan-flufenamide) plus dexamethasone has been approved by the European Medicines Agency for triple-class-refractory MM patients after ≥ 3 prior therapies, but current data from real-world settings are scarce. We herein report data from a single-center experience of 17 relapsed/refractory MM patients treated with melflufen-dexamethasone outside clinical trials between December 2021 and July 2025 in Bologna (Italy). The overall response rate was 41%. At a median follow-up (mFU) of 8 months, mPFS was 3.7 months (95% CI 1.8-NR) in the overall population, being 9.0 months (95% CI 7.8-NR) in responders (mFU 10 months), while mOS has not been reached (95% CI 13.5-NR) either in the total population or in subgroups. Notably, 11/17 patients received subsequent therapies (seven receiving novel immunotherapeutic approaches), achieving deeper and more durable responses than those receiving conventional regimens. Grade ≥ 3 hematologic toxicities were common (35% anemia, 53% neutropenia, 53% thrombocytopenia), while grade ≥ 3 nonhematologic events were less frequent (mainly fatigue: 6%, and infections: 23.5%). No secondary primary malignancies were recorded. Collectively, our data confirmed the efficacy previously reported with melflufen-dexamethasone and its manageable safety profile, even in elderly patients likely more fragile and more heavily pretreated than those included in the trials. Overall, melflufen-dexamethasone may represent a treatment option, especially for patients refractory to novel immunotherapies or those who are not ideal candidates to receive such treatments while still preserving access to subsequent T-cell redirecting therapies, thereby addressing a significant unmet need in this hard-to-treat patient population.
Caserta S, Martino EA, Skafi M
… +10 more, Alvaro ME, Bruzzese A, Amodio N, Lucia E, Olivito V, Labanca C, Mendicino F, Vigna E, Morabito F, Gentile M
Eur J Haematol
· 2026 Jun · PMID 41793237
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Primary refractory Diffuse Large B-Cell Lymphoma is associated with poor outcomes and limited responsiveness to conventional salvage therapies. Although CAR T-cell therapy represents the standard of care in this setting,...Primary refractory Diffuse Large B-Cell Lymphoma is associated with poor outcomes and limited responsiveness to conventional salvage therapies. Although CAR T-cell therapy represents the standard of care in this setting, a substantial proportion of patients cannot receive it despite meeting disease-related criteria. In this review, "unsuitable" refers to patients who are temporarily or functionally unable to undergo CAR T-cell therapy because of reversible clinical conditions, rapidly progressive disease requiring immediate cytoreduction, or logistical and social barriers, rather than permanent contraindications. For these patients, prompt alternative strategies are required. Conventional platinum-based or gemcitabine- and bendamustine-containing regimens retain a role for short-term disease control but offer limited durability. In contrast, novel antibody-based therapies, including polatuzumab-containing combinations, loncastuximab tesirine, and tafasitamab plus lenalidomide, have expanded treatment options with improved tolerability. Most notably, CD20 × CD3 bispecific antibodies represent a major therapeutic advance, providing off-the-shelf immune engagement with predominantly outpatient administration. From a practical perspective, early identification of reversible barriers to CAR T-cell therapy and timely use of bispecific antibodies or other antibody-based regimens are critical to achieve rapid disease control, preserve organ function, and, when feasible, restore eligibility for cellular therapy.
Epple D, Gall K, Paschke L
… +6 more, Kolb HJ, Wawer A, Knabe H, von Luettichau I, Hauer J, Thiel U
Eur J Haematol
· 2026 Jun · PMID 41787746
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INTRODUCTION: Allogeneic stem cell transplantation (allo-SCT) and donor lymphocyte infusions (DLI) can elicit a graft-versus-leukemia (GvL) effect in pediatric patients with hematological malignancies. We report our sing...INTRODUCTION: Allogeneic stem cell transplantation (allo-SCT) and donor lymphocyte infusions (DLI) can elicit a graft-versus-leukemia (GvL) effect in pediatric patients with hematological malignancies. We report our single-center experience with prophylactic DLI in high-risk pediatric patients with leukemia or lymphoma, focusing on feasibility, safety, and efficacy. METHODS: In total, 10 high-risk patients received prophylactic DLI following allo-SCT. Donors were either matched (n = 5) or haploidentical (n = 5). CD3+ T-cell doses of up to 1 × 10 cells/kg body weight were administered, in some cases over extended periods exceeding three years. RESULTS: The treatment was associated with a favorable toxicity profile. In our cohort, 40% of patients developed moderate acute (n = 2) or chronic (n = 2) graft-versus-host disease (GvHD); no cases of severe or high grade GvHD occurred. Given the high-risk profile of our cohort, outcomes were encouraging, with relapse-free survival (RFS) of 70% and overall survival (OS) of 80% at a median follow-up of 20.5 months. Especially, the two subgroups of patients with acute myeloid leukemia (AML) after relapse and patients who were transplanted in first complete remission (CR1) showed outcomes superior to currently reported data. One AML patient, who had experienced three relapses, received prophylactic DLI after a third allo-SCT and remains in complete remission (CR), more than 3 years after the last allo-SCT. CONCLUSION: These data suggest that prophylactic DLI may represent a safe and effective treatment option for pediatric patients with hematological malignancies at high risk of posttransplant relapse.
Matteucci A, Mariani MV, Pandozi C
… +12 more, Bonanni M, Frazzetto M, Pierucci N, La Fazia VM, Bruti RM, Palombi M, Vernile A, Lavalle C, Vizza CD, Fedele S, Nardi F, Colivicchi F
BACKGROUND: Whether long-term oral anticoagulation (OAC) is necessary after apparently successful atrial fibrillation (AF) ablation remains uncertain. Guidelines recommend continuation based on CHADS-VASc score rather th...BACKGROUND: Whether long-term oral anticoagulation (OAC) is necessary after apparently successful atrial fibrillation (AF) ablation remains uncertain. Guidelines recommend continuation based on CHADS-VASc score rather than procedural success, yet contemporary evidence, including randomized trials, has produced conflicting results. We aimed to provide an updated and comprehensive assessment of OAC discontinuation following AF ablation. METHODS: We conducted a systematic review and meta-analysis in patients who discontinued versus continued OAC after AF ablation. Outcomes included thromboembolic events (TE) and major bleeding events (MBE). Random-effects models with Hartung-Knapp correction were applied. Heterogeneity, publication bias, influence analyses, subgroup analyses, and risk-of-bias domains were assessed. RESULTS: In 28 studies (267 443 patients), OAC discontinuation significantly reduced the composite of TE and MBE (RR 0.44, 95% CI 0.32-0.61), driven by a marked decrease in bleeding (RR 0.25, 95% CI 0.16-0.39), without excess thromboembolic risk (RR 0.84, 95% CI 0.64-1.12). Findings remained consistent across subgroup analyses (study design, CHADS-VASc, geographic region), with sensitivity and meta-regression confirming robustness and no significant effect modifiers. Funnel plots showed no significant asymmetry for TE, whereas MBE demonstrated evidence of small-study effects. CONCLUSIONS: Discontinuation of OAC after successful AF ablation markedly reduces MBE without a statistically significant increase in TE, highlighting the need for individualized post-ablation anticoagulation strategies. Randomized trials are needed to confirm the safety of tailored oral anticoagulant discontinuation in selected patients, supported by careful long-term follow-up and shared decision-making.
Quinn SJ, Cardwell C, Anderson LA
… +1 more, McShane C
Eur J Haematol
· 2026 Jun · PMID 41787687
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Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic pre-cancerous condition that precedes plasma cell dyscrasias, including multiple myeloma (MM). Current clinical guidelines report that MGUS's r...Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic pre-cancerous condition that precedes plasma cell dyscrasias, including multiple myeloma (MM). Current clinical guidelines report that MGUS's rate of malignant progression to haematological malignancy (HM) is ~1% per year; however, reported rates have varied widely. To address this discrepancy, a systematic review was conducted, investigating MGUS's rate of malignant progression to HM and MM alone. Four electronic databases were searched from inception to 28 March 2024 for articles reporting these outcomes; articles were summarised using meta-analysis and narrative synthesis. Findings were incorporated from n = 46 studies, published between 1991 and 2024 and conducted across n = 17 countries. Median follow-up ranged from 1.3 to 34.2 years and sample sizes ranged from n = 63 to 17,963. In random-effects meta-analysis, n = 13 studies reported on MGUS progression to HM and n = 12 reported on progression to MM. The overall estimates of malignant progression events were 12 per 1000 person-years to HM, equivalent to 1.2% per year (95% CI: 1.0%-1.5%) and 8 per 1000 person-years to MM or 0.8% per year (95% CI: 0.7%-1.1%), with substantial heterogeneity between studies (I: 96.7% and 95.8%, respectively). Progression rates varied widely in narrative synthesis; at 10 years, studies reported annual MGUS progression rates of 6.6%-33.6% to HM and 7.0%-28.5% to MM. While progression rates aligned with clinical guidelines overall, studies' varied findings present opportunities for further research, exploring the impact of world region, follow-up duration, and study methods. Considering this, caution should be taken when informing clinicians and patients about the risk of progression from MGUS to MM.
Multiple myeloma (MM) is a hematologic malignancy manifested by proliferation of clonal plasma cells leading to end-organ damage. Despite significant advancements in therapeutics, it remains incurable. Cellular therapies...Multiple myeloma (MM) is a hematologic malignancy manifested by proliferation of clonal plasma cells leading to end-organ damage. Despite significant advancements in therapeutics, it remains incurable. Cellular therapies such as chimeric antigen receptor (CAR-T) therapy and T-cell engager (TCE) therapies have delivered high overall response rates, but almost all patients relapse and subsequent options are limited particularly in view of the increasing prevalence of prior exposure to anti-BCMA agents and immunomodulator (IMiD) therapies. Our retrospective review of 12 patients between January 2024 and December 2025 who received a combination of talquetamab, elranatamab, or teclistamab with pomalidomide found that 11 of 12 had an overall response, of whom 6 had very good partial response or better at median follow-up of 9.9 months. All 12 patients were prior exposed to pomalidomide, of whom 10 had been exposed to prior CAR-T with a median of 7 prior lines of therapy. Safety profiles were favorable: 6 patients experienced Grade 1 CRS, 7 experienced Grade III neutropenia, and 7 of 8 patients receiving talquetamab experienced on-target, off-tumor side effects like dysgeusia and skin dryness.
Ehlers LH, Levin MD, van der Klift M
… +4 more, Jensen MB, Tran HTT, Kater AP, Niemann CU
Eur J Haematol
· 2026 Jun · PMID 41740591
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The GAIA-CLL13 trial showed that venetoclax-obinutuzumab (Ven-O) based regimens, with or without ibrutinib, offer superior efficacy compared to chemoimmunotherapy (CIT) with regards to progression free survival (PFS) in...The GAIA-CLL13 trial showed that venetoclax-obinutuzumab (Ven-O) based regimens, with or without ibrutinib, offer superior efficacy compared to chemoimmunotherapy (CIT) with regards to progression free survival (PFS) in fit, treatment-naïve (TN) CLL patients. However, their higher costs warrant a cost-effectiveness evaluation. This study assessed the cost-effectiveness of Ven-O versus venetoclax with rituximab (Ven-R), venetoclax-obinutuzumab-ibrutinib (Ven-O-I), and CIT in fit, TN CLL patients without TP53 aberrations across the Netherlands, Norway, and Denmark. A state-transition Markov model including later line treatment was applied to estimate costs, life years (LYs), and quality-adjusted life years (QALYs) over a 38-year horizon. Results were sensitive to long-term OS assumptions. In the base-case analysis, extrapolating OS and PFS for each treatment separately, all venetoclax-based treatments appeared cost-effective compared to CIT in all three countries. ICERs for Ven-R, Ven-O, and Ven-O-I versus CIT were €35 840, €32 513, €30 331 for the Netherlands, €39 881, €38 099, €26 381 for Norway, and €34 010, €37 804, €33 215 for Denmark. In the sensitivity analyses, however, cost-effectiveness was lost when only allowing separate OS and PFS extrapolations for statistically significant differences at 60-month follow-up. Furthermore, cost-effectiveness results were sensitive to varying assumptions about national willingness-to-pay (WTP) thresholds, IGHV-status, and time horizon. In conclusion, venetoclax-based treatments may be considered a cost-effective treatment option for fit, TN CLL patients without TP53 aberrations in the Netherlands, Norway, and Denmark, but the pricing process for targeted agents should take the uncertainty about cost-effectiveness into account when negotiating pricing of medication. Longer follow-up data is needed to address the uncertainties.
Eur J Haematol
· 2026 Jun · PMID 41736301
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Acalabrutinib, a second-generation Bruton's tyrosine kinase inhibitor (BTKi), is characterized by enhanced specificity and selectivity for BTK with minimal off-target effects, offering a significant evolution in the trea...Acalabrutinib, a second-generation Bruton's tyrosine kinase inhibitor (BTKi), is characterized by enhanced specificity and selectivity for BTK with minimal off-target effects, offering a significant evolution in the treatment of chronic lymphocytic leukemia (CLL). Its mechanism of action, a covalent binding to Cys481 within the BTK active site, ensures potent and sustained blockade of B cell receptor signaling, leading to disruption of key survival and proliferation pathways in malignant B cells. Long-term data from pivotal phase III trials confirmed the high efficacy of acalabrutinib-containing regimens in both treatment-naïve and relapsed/refractory CLL, showing durable progression-free survival, favorable overall survival rates, and low incidence of serious adverse events such as atrial fibrillation and hypertension, likely attributable to its improved selectivity, with limited immunosuppression and better tolerability leading to lower discontinuation rates compared to first-generation BTKi. Fixed-duration combination with acalabrutinib plus venetoclax, with or without obinutuzumab, has recently emerged as a highly efficacious strategy, providing sustained minimal residual disease (MRD) negativity with manageable toxicity, further supporting the clinical utility of acalabrutinib regimens. The demonstrated efficacy, robust safety, and flexibility of acalabrutinib in both continuous and fixed-duration regimens make it a cornerstone for individualized CLL management, enabling tailored treatment approaches based on patient- and disease-specific factors.
Myelodysplastic syndromes/neoplasms (MDS) constitute a very heterogeneous group of clonal myeloid neoplasms characterized by a variable clinical course and recurrent genetic abnormalities. Their treatment relies on risk...Myelodysplastic syndromes/neoplasms (MDS) constitute a very heterogeneous group of clonal myeloid neoplasms characterized by a variable clinical course and recurrent genetic abnormalities. Their treatment relies on risk classification as lower or higher-risk categories by the original International Prognostic Scoring System (IPSS) or the current revised (IPSS-R) or molecular IPSS-M. Higher-risk MDS (HR-MDS) are clonal hematopoietic disorders characterized by significant cytopenias, dysplastic changes, and a high propensity for progression to acute myeloid leukemia (AML). Up to 40% of them usually progress to AML within two years of diagnosis. Allogeneic stem cell transplantation (HSCT) remains the only potential cure and standard of care for eligible patients. Despite standard treatments such as Allo-HSCT and hypomethylating agents (HMAs), outcomes remain suboptimal. Recent advances have led to the development of novel therapeutic strategies, such as BCL-2 inhibitors (venetoclax), IDH1/2 inhibitors (ivosidenib, enasidenib), CD47 inhibitors (magrolimab), TIM-3 inhibitors (sabatolimab), XPO1 inhibitors (eltanexor), NEDD8-activating enzyme inhibitors (pevonedistat), TP53-targeted agents (eprenetapopt), liposomal chemotherapy (CPX-351), and oral HMA formulations. Combinations of hypomethylating agents with these new drugs, as first-line treatment, have to date not proven more efficacious than HMA monotherapy. This review summarizes the current therapeutic landscape on novel therapies for HR-MDS, highlighting their mechanism of action, efficacy, and demonstrates the unmet clinical need for more effective therapies.
Extramedullary disease (EMD) of multiple myeloma (MM) is a critical indicator of disease progression, with a complex pathophysiology involving tumor microenvironment dysregulation, chromosomal abnormalities, and aberrant...Extramedullary disease (EMD) of multiple myeloma (MM) is a critical indicator of disease progression, with a complex pathophysiology involving tumor microenvironment dysregulation, chromosomal abnormalities, and aberrant signaling pathway activation. Advances in detection technologies have significantly improved EMD diagnosis rates in recent years, but clinical treatment still faces challenges such as high drug resistance rates and difficulties in managing lesions at specific sites. This article systematically reviews the definition, classification, biological characteristics, pathophysiological mechanisms, diagnostic methods, current treatment strategies, and emerging therapeutic challenges of EMD. It emphasizes the interactions between different pathogenic factors and the heterogeneous therapeutic responses of various EMD subtypes, aiming to provide a comprehensive reference for clinical practice and research directions.
Ali MF, Naseer F, Hageen AW
… +14 more, Hayat S, Rashid Z, Momna FNU, Sawaira FNU, Riaz AA, Ahmad H, Eltawansy S, Hossain M, Ahmed T, Naveed MA, Munir MB, Chigurupati HD, Sattar Y, Neppala S
BACKGROUND: Extended-duration anticoagulation reduces recurrent venous thromboembolism (VTE) in cancer and non-cancer patients. Reduced-dose direct oral anticoagulants (DOACs) may be safer if they match efficacy with les...BACKGROUND: Extended-duration anticoagulation reduces recurrent venous thromboembolism (VTE) in cancer and non-cancer patients. Reduced-dose direct oral anticoagulants (DOACs) may be safer if they match efficacy with less bleeding risk. We conducted a systematic review and meta-analysis of trials comparing reduced-dose and extended-dose DOACs. METHODS: Randomized controlled trials comparing reduced-dose with extended-dose anticoagulation for secondary VTE prevention were systematically reviewed. Primary outcomes included recurrent symptomatic VTE, pulmonary embolism (PE), and deep vein thrombosis (DVT). Secondary outcomes included bleeding, adverse events, and all-cause mortality. Risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using random-effects models. Subgroup and leave-one-out sensitivity analyses explored heterogeneity and robustness. All analyses were conducted in R (version 4.3.1). RESULTS: Six RCTs (n = 9382) were included. Reduced-dose anticoagulation showed no statistically significant difference in recurrent VTE (RR 0.98, 95% CI 0.72-1.33), PE (RR 0.96, 95% CI 0.61-1.50), or DVT (RR 0.86, 95% CI 0.56-1.32) compared with extended-dose therapy. Major bleeding was significantly reduced (RR 0.68, 95% CI 0.48-0.98), as were clinically relevant non-major bleeding and any bleeding. All-cause mortality did not differ significantly. Heterogeneity was low to moderate across outcomes, and sensitivity analyses confirmed the stability of results. CONCLUSION: Reduced-dose anticoagulation demonstrated similar efficacy with improved safety compared with extended-dose therapy. These findings support individualized dose reduction strategies after extended anticoagulation. TRIAL REGISTRATION: ClinicalTrials.gov identifier: CRD420251081952.
Batyrbekova N, Landtblom AR, Hultcrantz M
… +3 more, Szulkin R, Dickman PW, Andersson TM
Eur J Haematol
· 2026 Jun · PMID 41717866
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BACKGROUND: Individuals with polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) face transformation risks to acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). While ol...BACKGROUND: Individuals with polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) face transformation risks to acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). While older age is linked to increased risk, it remains unclear whether risk increases with age or with disease duration. OBJECTIVES: To examine how age and disease duration affect AML and MDS transformation in MPN. METHODS: We used Swedish nationwide register data to model transformation rates as continuous functions of age and disease duration for each subtype and outcome. Cumulative incidences were estimated accounting for competing risk of death. RESULTS: This study included 7156 patients with PV, 6810 with ET, and 1080 with PMF diagnosed in 2001-2021. In PV and ET, AML rates increased with disease duration. In PMF, AML rates were highest soon after diagnosis and declined over time. The 10-year cumulative incidence of AML at diagnosis age 70 was 3.5% in PV, 4.7% in ET, and 18.2% in PMF; for MDS, it was 1.7%, 3.1%, and 10.7%, respectively. CONCLUSION: AML and MDS transformation risks vary by MPN subtype and depend on age and disease duration, with disease duration elevating AML risk in PV and ET; incorporating both factors is essential for individualized risk assessment.