European Journal of Haematology最新文献

Intravascular large B-cell lymphoma (IVLBCL) is a rare lymphoma with a poor prognosis. This retrospective study reports the clinicopathological characteristics and outcomes of six cases of IVLBCL diagnosed in a period of 8 years in a tertiary hospital. The mean age was 66 years, with no sex predilection. Dizziness, gait instability, and hepatosplenomegaly were the most common presentations. Laboratory and brain imaging findings were inconclusive for lymphoma in all cases. Brain biopsies were diagnostic in two cases, while skin biopsies led to diagnosis in three patients. Only one patient with hemophagocytic variant was diagnosed at autopsy. Histologically, atypical lymphocytes infiltrated deep small- and medium-sized vessels, showing positive staining for B-cell markers. All patients who received combined chemotherapy achieved a complete response. After a median follow-up of 4 years, four of six patients remain alive. This lymphoma represents a diagnostic challenge, requiring a high index of suspicion and a multidisciplinary approach.

Objective: This systematic review and meta-analysis aimed to evaluate the risk of thromboembolic events and assess the overall safety and effectiveness of avatrombopag in adult patients with immune thrombocytopenia using real-world evidence.

Methods: A systematic search was conducted following the PRISMA 2020 guidelines. Observational studies (2020-2024) on adults with primary immune thrombocytopenia treated with avatrombopag were included. Primary outcomes were thromboembolic complications and treatment response; secondary outcomes included time to response, treatment discontinuation, and adverse events. Random-effects meta-analyses were performed to synthesise pooled proportions and rates. Risk of bias was assessed using the ROBINS-Version 2 tool.

Results: Fifteen studies were included. The pooled proportion of patients with thromboembolic events was 2.82% (95% confidence interval: 1.61%-4.27%), with an incidence rate of 3.29 per 100 patient-years (95% CI: 1.81-5.08). Response and complete response were achieved by 80.0% and 92.0% of patients, respectively. The median time to response was 11 days, and the discontinuation rate was 18.9%. Adverse events occurred in 4.1% of patients.

Conclusion: In real-world practice, avatrombopag demonstrated high platelet response rates and a low pooled incidence of thrombotic events. These findings add real-world evidence on avatrombopag outcomes in adult immune thrombocytopenia.

Multiple myeloma (MM) is a clonal plasma cell malignancy that remains largely incurable despite major therapeutic advances. T-cell-redirecting bispecific antibodies (BsAbs) and chimeric antigen receptor T (CAR-T) cells have recently emerged as highly effective therapies in relapsed/refractory MM, inducing deep responses even in heavily pretreated patients. However, disease relapse, limited durability of response, and treatment-related toxicities remain frequent, underscoring the need to better understand mechanisms of resistance. Accumulating evidence indicates that the tumor microenvironment (TME) plays a central role in shaping BsAb efficacy in MM. Immunosuppressive cellular components, including regulatory T-cells, myeloid-derived suppressor cells, and dysfunctional antigen-presenting cells, as well as inhibitory cytokines, hypoxia, and metabolic constraints within the TME, profoundly impair T-cell activation, expansion, and persistence following BsAb engagement. In addition, chronic CD3 stimulation within the TME may promote T-cell exhaustion, contributing to suboptimal responses and disease progression. This review focuses on the dynamic interplay between BsAbs and the MM TME, highlighting how microenvironment-driven immune suppression, antigen escape, and impaired T-cell fitness influence clinical outcomes. We further discuss emerging strategies designed to overcome these barriers, including rational combination approaches, immunomodulatory agents, and next-generation trispecific antibodies that enhance co-stimulation or dual-antigen targeting. Understanding and therapeutically modulating the TME represents a critical step toward improving the depth, durability, and safety of BsAb-based therapies in MM.

Acute chest syndrome (ACS) is a severe complication of sickle cell disease (SCD) associated with significant morbidity and mortality, necessitating optimized prevention and management strategies for improved patient outcomes. This review does not evaluate red blood cell exchange, as no randomized controlled trials meeting our inclusion criteria reported outcomes for this intervention. A thorough literature review identified interventions for ACS in SCD patients. Seventeen randomized controlled trials (RCTs) underwent assessment using the Cochrane Risk of Bias 2 tool, and a frequentist network meta-analysis was conducted to compare interventions. The use of hydroxyurea and simple transfusion was associated with a lower proportion of patients who developed ACS during the study period compared with standard care (RR: 0.42, 95% CI [0.20-0.86]; RR: 0.31, 95% CI [0.12-0.75], respectively). Intravenous dexamethasone was associated with a lower risk of persistent fever, reduced need for blood transfusion, and shorter durations of both opioid and oxygen therapy, as well as a shorter in-hospital stay (p < 0.01 for all comparisons). When compared with standard care, hydroxyurea was associated with reduced requirement for blood transfusion (RR: 0.17, 95% CI [0.04, 0.73]), with a similar association observed for intravenous dexamethasone (RR: 0.19, 95% CI [0.05, 0.77]). No significant associations were identified between any treatment and rates of hospitalization or readmission. This study offers insights into ACS treatment efficacy and safety in SCD patients. Hydroxyurea and transfusion strategies demonstrated the strongest evidence for reducing acute chest syndrome risk. Corticosteroids were associated with improved inpatient outcomes in predominantly pediatric populations, but concerns regarding potential rebound pain and rehospitalization warrant cautious interpretation. Larger trials are required before routine steroid use can be broadly recommended.

In the phase 2, double-blind, randomized controlled BEYOND trial (NCT03342404), luspatercept increased hemoglobin levels in patients with non-transfusion-dependent β-thalassemia (NTDT). This study assessed long-term effects of luspatercept on patient-reported outcomes (PROs), using data from BEYOND and patients who continued luspatercept treatment in the phase 3b long-term follow-up (LTFU) study (NCT04064060). In BEYOND, patients received luspatercept or placebo Q3W for ≥ 48 weeks. PRO instruments included NTDT-PRO (BEYOND only), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), and 36-Item Short Form Survey (SF-36). Mixed-effects models with repeated measures estimated least squares mean changes from baseline in PROs. PROs were evaluable in 144 patients (luspatercept 95, placebo 49) from BEYOND and 58 (luspatercept) from LTFU. Luspatercept improved NTDT-PRO tiredness/weakness and shortness of breath domain, FACIT-F fatigue subscale, and SF-36 vitality scores versus placebo through double-blind treatment (generally maintained through week 96). In LTFU patients, significant, meaningful improvements from baseline in FACIT-F fatigue subscale and SF-36 vitality scores were observed within 12 weeks of treatment initiation and maintained for up to 5 years. Other FACIT-F and SF-36 domains improved or were maintained throughout LTFU. Luspatercept offers rapid and durable benefits by improving anemia-related symptoms and quality of life in patients with NTDT. Trial Registration: ClinicalTrials.gov Identifier: NCT03342404; NCT04064060.

Background and aims: Retroperitoneal Infantile Fibrosarcoma (RIFS) is a rare, locally aggressive pediatric soft tissue tumor. Its retroperitoneal location poses challenges due to proximity and potential invasion of critical structures such as the inferior vena cava (IVC). This study aims to illustrate the range of multidisciplinary management strategies and evolving therapeutic approaches.

Methods: We conducted a retrospective case series of infants diagnosed with RIFS and treated at our tertiary center. Clinical presentation, imaging findings, histopathology, treatment modalities (including chemotherapy, surgery, interventional radiology, targeted therapies), and follow-up data were analyzed.

Results: Three infants with histologically confirmed RIFS were identified, with a median age at diagnosis of 2 months (range: 0-8 months). Diagnosis was established through open surgical biopsy. Management was individualized and multimodal, including neoadjuvant chemotherapy, surgical resection, interventional radiology procedures for symptom control, and, in the most recent case, targeted molecular therapy guided by genetic profiling.

Conclusions: Management of RIFS has significantly evolved over the last decade. Advances in surgical techniques combined with the integration of interventional radiology and novel targeted therapies allow a nuanced balance between maximizing oncological control and minimizing surgical morbidity. Multidisciplinary individualized treatment is essential to optimize outcomes in this rare and challenging pediatric tumor.

Leukemia is the most common childhood cancer, accounting for one-third of malignancies in this age group. Testicular infiltration in pediatric leukemia patients represents a manifestation of leukemic dissemination beyond the bone marrow and can occur at diagnosis or be a sign of relapse. Testicular infiltration may occur particularly in specific leukemia subtypes, such as acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) and is an important prognostic factor, as it may indicate an increased risk of leukemia relapse. Therefore, rigorous follow-up is essential to detect testicular infiltration early and initiate appropriate treatment. This study aims to evaluate cases of leukemia with testicular infiltration in two pediatric oncology referral centers in two different countries. We conducted a retrospective study of patients presenting with secondary testicular infiltration due to leukemia over a 14-year period (January 2010 to December 2023). During the study period, we identified 24 patients who developed testicular infiltration secondary to leukemia. All cases of testicular infiltration were diagnosed at the time of disease relapse. Fourteen patients presented with isolated testicular relapse, while the remaining patients had additional relapse sites in combination with testicular recurrence: bone marrow (10 cases) and central nervous system (2 cases). The mean age at diagnosis was 7.91 years. The average leukocyte count at diagnosis was 56 211/mm³, with only five patients presenting with leukocyte counts above 100 000/mm³. Four children (16.6%) were diagnosed with T-cell ALL, 20 (83.4%) with B-cell ALL. Fifteen patients (62.5%) underwent hematopoietic stem cell transplantation, including two haploidentical transplants. Twelve patients (50%) died-three due to disease progression and one from disseminated fusariosis. Data regarding the cause of death were unavailable for the remaining patients. The average follow-up duration was 5.87 years, with an event-free survival of 2.085 years. Although rare, testicular infiltration in leukemia patients is a clinically significant phenomenon that may affect both prognosis and quality of life. Early diagnosis and appropriate treatment of the underlying leukemia are crucial to improve outcomes. Monitoring of testicular function and fertility-related concerns must also be addressed comprehensively in patient management. Future studies with larger cohorts and standardized management protocols are essential to establish clear guidelines for the diagnosis, treatment, and follow-up of patients with testicular relapse secondary to ALL. Given the low number of cases and the diversity of local resources worldwide (especially regarding radiotherapy and endocrine follow up), the best approach for each patient should be determined in multidisciplinary team discussions.

Relapsed and refractory multiple myeloma (RRMM) remains associated with poor outcomes, particularly in patients exposed or refractory to proteasome inhibitors, immunomodulatory agents, and anti-CD38 monoclonal antibodies. Targeting B-cell maturation antigen (BCMA) has emerged as an effective therapeutic strategy, prompting the development of bispecific antibodies that redirect T-cell cytotoxicity toward malignant plasma cells. Elranatamab is a humanized BCMA × CD3 bispecific antibody that has demonstrated clinically meaningful activity in heavily pretreated RRMM. This review summarizes and critically appraises available evidence on elranatamab, focusing on its mechanism of action, clinical efficacy, safety profile, patient-reported outcomes, and comparative positioning within the evolving BCMA-directed treatment landscape. Across studies, elranatamab has shown high response rates, durable disease control, and manageable toxicity, with predominantly low-grade cytokine release syndrome and limited neurotoxicity when administered with step-up dosing. Emerging data indicate preserved efficacy in patients previously exposed to BCMA-targeted therapies and feasibility in selected high-risk populations, including those with severe renal impairment. Nevertheless, uncertainties remain regarding optimal sequencing, long-term survival benefit, infection risk management, and mechanisms of resistance. Overall, elranatamab represents a valuable addition to the therapeutic armamentarium for RRMM. Ongoing studies and real-world experience will be critical to refine its positioning, identify patients most likely to benefit, and define its role in combination strategies.

Introduction: Allogeneic hematopoietic stem cell transplantation (HSCT) offers curative potential for many hematological malignancies; however, outcomes may be adversely affected by infections and transplant-associated complications, contributing to non-relapse mortality (NRM). Innovative digital approaches for outpatient surveillance may support earlier detection of complications and thereby help reduce NRM.

Case presentation: We report on a 73 year-old Caucasian patient who underwent allogeneic HSCT for acute myeloid leukemia in complete remission following non-myeloablative conditioning. The patient participated in the interventional study "Cross-sectoral care for patients with hematological diseases following innovative cell therapy" (SPIZ), which evaluates digital surveillance after cellular therapies. SPIZ comprises daily remote monitoring of vital signs, medication adherence, and symptoms using a multimodal approach integrating an eHealth system (patient smartphone app and caregiver monitoring dashboard), home visits, video consultations, and regular case conferences with referring physicians during follow-up. Eight months post-HSCT, during an inpatient stay at an orthopedic rehabilitation center, the patient reported increasing dyspnea and cough via the app. In response, the SPIZ team initiated immediate transfer to the transplant center. Diagnostic work-up revealed pneumonia caused by aspergillus fumigatus and coronavirus, and progression of pre-existing pulmonary graft-versus-host disease (GvHD), confirmed by computed tomography and spiroergometry. Early detection and prompt transfer enabled rapid initiation of antifungal therapy and intensified GvHD management. The patient was discharged with improved general condition and respiratory function, without further septic complications.

Conclusion: Innovative digital surveillance is an effective tool for outpatient monitoring after cellular therapies, facilitating early detection and intervention and potentially reducing NRM, particularly in high-risk patients.

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 × 10⁹/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 × 10⁹/L yielded a high sensitivity of 97% for clinically meaningful eosinophilia.

Conclusions: These findings support considering a threshold of 1.5 × 10⁹/L or higher for hematology referral, especially in low-risk and asymptomatic patients, though external validation is needed.