European Journal of Haematology最新文献

Identifying patients eligible for front-line clinical trials with diffuse large B-cell lymphoma (DLBCL) has been challenging, primarily due to increasingly stringent inclusion criteria and the limitations of the International Prognostic Indices in identifying patients who are unlikely to achieve long-term remission after standard treatment. We aimed to assess the impact of using improved eligibility criteria established through a US-based Delphi-method survey to identify real-world DLBCL patients eligible for clinical trials. Additionally, we developed a predictive model to assess the individual risk of trial-eligible patients with an online calculator. Of 5341 potential trial candidates identified from the Danish Lymphoma Registry, 4063 patients (76.1%) were trial-eligible if the recommended eligibility criteria were applied. Among excluded patients, 7.9% would be excluded due to inadequate organ function. To develop a predictive model for progression-free survival, we randomly divided the population into a training and a validation cohort (3:1 ratio). Then, the Delphi Trial Prognostic Index (DTPI) was developed based on eight clinical and laboratory variables, demonstrating superior performance compared to the International Prognostic Indices. Our prediction model, which incorporates less restrictive eligibility criteria and utilizes an online calculator, was designed to more accurately predict outcomes for potential candidates eligible for first-line clinical trials.

Objectives: To determine the diagnostic value of disclosing monotypic T-cell populations by expression analysis of the constant region 1 of T-cell receptor β (TRBC1) by flow cytometry, for the detection of T-cell neoplasms, in a routine hematopathology practice setting.

Methods: A panel of antibodies ECD-CD16/PECy5.5-CD4/PECy7-CD2/APCAF700-CD7/KO-CD8/FITC-TCRγδ/PE-TRBC1/APC-CD26/APC-CD57/APC-CD30/APCH7-CD45/BV421-CD3 was applied. One thousand and twenty-nine cases investigated during 26 months were reviewed and categorized as monotypic or polytypic depending on the expression of TRBC1 in all identifiable CD3+ T-cell subsets.

Results: Although TRBC1 restriction proved to be sensitive (90.7%) with a high negative predictive value (99.1%), in some T-cell neoplasms, particularly those with significant inflammation, including angioimmunoblastic T-cell lymphoma, monotypic T-cells were not detected. The specificity was high (95.6%) albeit with a modest positive predictive value (67.1%), reflecting T-cell clones of uncertain significance (T-CUS) without T-cell neoplasm. Of these clones, 53.6% exhibited a T-cell large granular lymphocytic leukemia-like phenotype, most commonly found in the peripheral blood or bone marrow, while others were identified in association with unrelated primary tumors or other comorbidities. Seventy-nine percent of the T-CUS cases remained stable over time during 1-77 months of follow-up.

Conclusion: Including TRBC1 antibodies in a routine flow cytometry panel facilitates the identification of T-cell neoplasms. The analysis must be interpreted within its clinical context since T-cell lymphomas with a small and sometimes surface CD3-negative neoplastic T cell population, may display normal patterns of TRBC1-expression with a background of reactive T cells. Conversely, monotypic T-cells can be found in the absence of T-cell neoplasm.

Background: Identifying patients with a higher risk of recidivate/refractory Hodgkin lymphoma (R/R HL) is a challenge that needs to be addressed. The International Prognostic System (IPS) identifies patients with a poor prognosis in advanced stages, although its relevance has decreased due to advancements in modern treatment. The interim PET-2 scan after two chemotherapy cycles is now considered the most crucial prognostic tool, but it is only available after treatment initiation.

Methods: We investigate the role of clinical and inflammatory indices associated with clinical data in 212 HL patients, focusing on peripheral blood ratios.

Results: During follow-up, after a median of 60 months [3-213], 157 patients (74.1%) were in complete remission, and 55 were classified as R/R. SII (platelets × neutrophils/lymphocytes) ≥ 270, IgM < 50 mg/dL, male gender, and extranodal localization correlate with higher relapse and refractory rates. Assigning one point to each variable, a new prognostic score (ME-IPS) was developed, recognizing three risk classes. A total of 135 (63.7%) patients belonged to the low-risk class (0-1 points), 55 (25.9%) to intermediate (2 points), and 22 (10.4%) to high (3-4 points). The median PFS for the three groups was statistically different (not achieved vs. 89 vs. 8.8 months, p < 0.001), with a 5-year cut-off of 83%, 67%, and 27% (p < 0.001). ME-IPS, validated against the traditional IPS, performs better in identifying high-risk patients with data collected at diagnosis.

Conclusion: Combining the ME-IPS model with PET-2 may provide a more effective tool for HL prognosis, particularly in cases of advanced disease, and guide treatment decisions in clinical practice.

Infections remain a leading cause of morbidity and mortality in patients with chronic lymphocytic leukemia (CLL), reflecting both intrinsic immune dysfunction and therapy-related immunosuppression. The pathogenesis of immunodeficiency in CLL is multifactorial: neoplastic B cells impair humoral immunity, T cells are functionally exhausted, and innate immune cells, particularly neutrophils and NK cells, display profound defects. Beyond impaired pathogen defense, these immune alterations actively support leukemic cell survival and promote a tolerogenic microenvironment. The advent of targeted therapies has reshaped the infectious risk profile. Bruton's tyrosine kinase inhibitors (BTKis) and venetoclax have largely replaced chemotherapy, reducing classic opportunistic infections but introducing new challenges. BTKis are associated with invasive fungal infections and increased pneumonia risk in combination regimens, while venetoclax frequently induces profound neutropenia. Anti-CD20 monoclonal antibodies cause long-lasting B-cell depletion and viral reactivation. These evolving risks demand nuanced approaches to prevention. Prophylactic strategies must be individualized. Antiviral prophylaxis is warranted with anti-CD20 antibodies and BTKis, and Pneumocystis jirovecii pneumonia (PJP) prophylaxis remains essential with fludarabine, cyclophosphamide, and rituximab (FCR) or prolonged corticosteroid therapy. Antifungal prophylaxis is not routinely indicated in CLL but may be considered in high-risk patients on BTKis or with refractory disease. Immunoglobulin replacement therapy (IgRT) reduces recurrent bacterial infections in patients with hypogammaglobulinemia, while vaccination-though often limited by suboptimal responses-remains the cornerstone of prevention. Timing before therapy or during treatment-free intervals is critical, and newer formulations, such as conjugate pneumococcal and recombinant zoster vaccines, are preferred. Future directions include developing predictive biomarkers of infection risk and vaccine responsiveness, integrating immune monitoring into clinical trials, and exploring strategies to modulate neutrophil plasticity and restore T-cell function. Until then, a pragmatic, risk-adapted approach combining vigilance, prophylaxis, immunoglobulin replacement, and optimized vaccination offers the best safeguard for patients with CLL.

Since 2004, patients receiving imatinib with relapse in non-marrow sites were given dasatinib to preserve control of leukemic marrow. Remissions in CNS and other organs began to be reported and are continuously observed to present. With resistance to one BCR::ABL1 tyrosine kinase inhibitor and sensitivity to a dual BCR::ABL1/SRC inhibitor recognized, we undertook a retrospective observational study of all reported patients with EML given dasatinib ± routine therapies used over 50 years. We elicited remission durations from authors. One hundred and sixty-three patients (150 Ph'+, 13 Ph'- negative leukemias) received dasatinib ± conventional EML treatments. All but six cases reported disappearance of EML involvement, documented by MRI, CSF, PET/CT in 10, and autopsy in 2. To date, 36 EML remissions have lasted 2+-11+ years (15 > 4 years). Thirty-four of the responding patients had post-dasatinib transplants and 3 CAR-T therapy. The tyrosine kinase inhibitor overexpressed in our prior RNAseq studies of EML tissue was LCK, a SRC kinase target of dasatinib known to be present in CNS, nerves, and some cancers. We present published data to support LCK as one possible tissue target in EML. As there has never been any durably effective treatment for EML, these observations merit prospective trials to validate the observed success of dasatinib and determine the role of additional therapies including cellular therapies. Dasatinib is a potentially practice-changing targeted therapy for EML. Finding and eradicating EML could increase the possibility of lengthy disease-free survival.

Objective: To evaluate the safety and efficacy of the C5-inhibitor crovalimab in patients with paroxysmal nocturnal hemoglobinuria (PNH).

Methods: PubMed, Scopus, Web of Science, and Cochrane Library were searched for studies on the use of the C5 inhibitor crovalimab in patients with PNH. Outcomes included hemolysis control (HC: LDH ≤ 1.5 × ULN), stabilized hemoglobin (SH), transfusion avoidance (TA), and safety endpoints. Pooled estimates were calculated using random-effects models with 95% confidence intervals (CIs), and heterogeneity was assessed via the I² statistic.

Results: Four studies involving 275 patients were included. Pooled prevalence of HC was 83% (95% CI: 0.75-0.91), SH in 61% (95% CI: 0.48-0.75), and TA in 65% (95% CI: 0.56-0.74). At least one any-grade Adverse Event (AEs) occurred in 90% (95% CI: 0.78-0.99), while Serious Adverse Events (SAEs) occurred in 14% (95% CI: 0.05-0.23). Treatment-related AEs affected 47%, and infections occurred in 50%. Grade 3-5 AEs were seen in 19%, dose modifications in 2%, and treatment discontinuation in 0.4%.

Conclusion: Crovalimab showed encouraging efficacy and an acceptable safety profile in patients with PNH, supporting its role as a promising treatment option in PNH.

Objectives: Secondary hemophagocytic lymphohistiocytosis (sHLH) is a severe hyperinflammatory syndrome requiring rapid recognition and treatment. Despite the expanding availability of biologic and cytokine-directed therapies, etoposide-based immunochemotherapy remains the primary treatment in many pediatric centers. This study evaluated the efficacy, response kinetics, and clinical outcomes of etoposide-based therapy in children with sHLH.

Methods: We retrospectively analyzed 32 pediatric patients diagnosed with sHLH between 2018 and 2023 at a tertiary center. Diagnosis was based on HLH-2004 criteria; primary HLH was excluded through genetic testing when available. All patients received dexamethasone and etoposide, with cyclosporine A initiated after Week 1. Trigger-directed therapies included rituximab for EBV-HLH and anakinra or tocilizumab in selected hyperinflammatory states. Laboratory dynamics (ferritin, fibrinogen, platelets, and absolute neutrophil count), clinical responses, relapse, hematopoietic stem cell transplantation (HSCT), and overall survival (OS) were assessed.

Results: The median age was 38 months; 62.5% were male. Triggers included EBV (34%), other viral infections (19%), rheumatologic disease/MAS (16%), bacterial infection (13%), and malignancy (9%). By Week 4, ferritin decreased from 6480 to 1240 ng/mL and fibrinogen increased from 122 to 286 mg/dL (p < 0.001). Fever resolved in 90% by Week 2, and 81% achieved complete laboratory response. During a median follow-up of 18 months, relapse occurred in 18.8% and HSCT was required in 15.6% of patients. Overall survival was 91% at 1 year and 86% at 2 years. Adverse events were consistent with expected etoposide-related toxicities.

Conclusion: Etoposide-based immunochemotherapy provided rapid disease control and favorable survival in pediatric sHLH. These findings support the continued relevance of etoposide while underscoring the need for risk-adapted approaches integrating trigger-directed therapy, cytokine inhibitors, and timely HSCT in selected patients.

Introduction: Following treatment, relapse of Multiple Myeloma (MM) occurs due to measurable residual disease (MRD). As therapeutic options expand, advances in response assessment become more critical, necessitating more sensitive MRD detection methods.

Method: This study aimed to improve the efficiency and sensitivity of a flow cytometry assay for MM MRD detection in blood and bone marrow. To achieve this, three pre-enrichment methods were compared using 32 samples from patients with active MM and 122 samples from MM patients in remission. The methods compared were the Euroflow recommended erythrocyte bulk lysis (BL) method, density gradient medium (DGM) separation and negative selection (NS).

Results: By removing granulocytes, DGM facilitated the processing of a larger starting quantity of white blood cells (WBCs) (> 60 × 10⁶) compared to BL (20 × 10⁶), achieving greater analytical sensitivity with a limit of detection of 5.2 × 10^-7 vs. 2 × 10^-6. DGM separation also features a shorter processing time and is more cost-effective. Although NS can also process large quantities of WBCs, the need for extra processing steps and substantially higher costs made this method the least suitable choice for clinical implementation.

Conclusion: Pre-enrichment via DGM separation can cost-effectively reduce sample processing times and significantly increase the analytical sensitivity of MM MRD analysis.

Objectives: Although Advancements in the Treatment of Hemoglobinopathies have Considerably Increased Life Expectancy, Hormonal and Pubertal Development Have Been Continuously Affected by Complications From Transfusion-Related Iron Overload and Cytotoxic Therapies. This Study Investigated the Association Between Serum Ferritin Levels and Pubertal Progression in Patients With Thalassemia and Sickle Cell Disease (SCD).

Methods: Data Collected From 10 Hospitals in Austria, Germany, and Switzerland From 2012 to 2020 Were Retrospectively Analyzed. We Enrolled 140 Individuals (Median Age: 16.5 Years) With Thalassemia or SCD.

Results: Overall, Delayed Puberty Was Observed in 14.7% (6.7% Females; 21.1% Males) and 13.2% of Patients With Thalassemia and SCD (6.9% Females; 20.8% Males), respectively. Gonadal Insufficiency Was Found in 13.3% and 8.6% of Females With Thalassemia and SCD, Respectively. Abnormal Growth Trajectories Were Observed in 32.5% (28.5% Females; 36.8% Males) and 18.7% of Patients With Thalassemia and SCD (13.3% Females; 23.5% Males), respectively. A Statistically Significant Association Was Found Between Elevated Ferritin Levels and Growth Delays in Patients With Thalassemia. Notably, Tanner Staging Data Were Missing in 80.7% of the Medical Records.

Conclusions: Our Results Indicated the Need for Comprehensive Pubertal Screening and Underscored the Importance of Robust Endocrine Follow-Up Care in Individuals With Hemoglobinopathies.