European Journal of Haematology最新文献

Background: In the earlier PROTECT VIII Kids study (NCT01775618), damoctocog alfa pegol was efficacious for prevention and treatment of bleeds in children aged < 12 years with severe haemophilia A.

Objective: Assess the safety of damoctocog alfa pegol, including hypersensitivity and loss of efficacy (LoE) due to an immune response to polyethylene glycol, in children aged 7 to < 12 years with severe haemophilia A.

Methods: Alfa-PROTECT is a phase 3, multicentre, open-label, single-arm study (NCT05147662). Primary endpoint was the incidence of adverse events of special interest (AESI) leading to discontinuation during the first 4 exposure days.

Results: Overall, 35 children enrolled; 32 completed the 6-month study, 21 (60%) reported ≥ 1 AE. Median (range) treatment duration was 182 (172-198) days. All AEs were mild/moderate; 3/35 children (8.6%) had study drug-related AEs. One (2.9%) LoE event was considered an AESI, and led to temporary treatment interruption. No AEs resulted in study drug discontinuation. The probability of < 5% of patients experiencing an AESI was 92.2%. Bleed protection was maintained with damoctocog alfa pegol prophylaxis.

Conclusions: These data confirm the safety profile of damoctocog alfa pegol in children aged 7 to < 12 years with severe haemophilia A. Secondary endpoints indicate treatment was efficacious.

Trial registration: The Alfa-PROTECT trial is registered at ClinicalTrial.gov (NCT05147662).

Background: Immunomodulatory agents (IMiDs) are a cornerstone in the successful management of multiple myeloma (MM). However, acquired IMiD resistance leading to disease relapses remains a major barrier. Hydrogen peroxide generation and oxidative stress are key mediators that determine IMiD's effectiveness in MM. Iron plays a key role in the generation of oxidative stress; therefore, cellular iron levels are tightly governed. FTH1 is the major iron storage protein that tightly regulates cellular iron availability. Hence, the present study is targeted to investigate the role of FTH1 in MM and IMiD resistance.

Methods: IMiD-sensitive and IMiD-resistant MM cells were analyzed for expression of iron-metabolism genes. CRISPR-cas9-mediated knockout of FTH1 was performed and the after-effects were assessed through multiple experiments.

Results: Initial analysis showed a positive correlation between FTH1 expression and IMiD resistance in MM cells. FTH1-KO reduced IMiD sensitivity in the KMS11 cell line but had no effect on the RPMI8226 cell line. RNA-seq data showed downregulation of ER-stress and calcium signaling genes after FTH1-KO. Further, KMS11-FTH1KO cells exhibited lower intracellular ROS, labile-iron, and mitochondrial superoxide levels along with increased CD63, suggesting activation of L-ferritin secretory pathways.

Conclusion: Data reveals a link between FTH1, labile iron, ROS, and IMiD resistance in MM cells.

Follicular lymphoma (FL), traditionally considered an indolent yet incurable malignancy, is experiencing a substantial evolution in its therapeutic landscape with the emergence of chemo-free treatment strategies. These novel approaches challenge conventional chemotherapy-based paradigms and offer promising alternatives for both newly diagnosed and relapsed/refractory (RR) FL patients. Among these innovations, bispecific antibodies (BsAbs) have demonstrated compelling efficacy while providing practical advantages, including outpatient administration and generally manageable safety profiles. Chimeric antigen receptor (CAR) T-cell therapies have further expanded the therapeutic armamentarium, achieving unprecedented response rates in heavily pretreated and high-risk populations, although their implementation remains limited by logistical complexity and high associated costs. Additional targeted agents-such as Enhancer of zeste homolog 2 (EZH2) inhibitors, lenalidomide, and Bruton tyrosine kinase (BTK) inhibitors-also contribute meaningfully to chemo-free treatment options, particularly within combination regimens that may enhance clinical benefit. Despite these advances, several challenges persist. Early disease progression (POD24) remains one of the most powerful prognostic determinants in FL. The FLIPI-C model, incorporating machine-learning-derived risk stratification, has shown promise in identifying high-risk patients who may benefit most from innovative approaches. Introducing chemo-free therapies earlier in the treatment algorithm may improve outcomes for these patients while mitigating the long-term toxicities associated with conventional chemotherapy. Ongoing validation through prospective clinical trials and real-world evidence will be essential to define the optimal integration of these therapies. Overall, this evolving paradigm highlights the urgent need for continued innovation, multidisciplinary collaboration, and equitable access to ensure that the full potential of chemo-free strategies can be realized for patients with this complex disease.

Background: Hemophagocytic lymphohistiocytosis (HLH) is a rare hyperinflammatory syndrome. It is a severe condition with a challenging diagnosis in the intensive care unit (ICU), for which current recommendations rely on fulfilling five of eight HLH-2004 criteria.

Methods: Our single-center retrospective cohort included adults admitted to the ICU in whom HLH was diagnosed, suspected, or excluded. The primary outcome was the prevalence of HLH in the ICU according to the HLH 2004 criteria. Additional factors analyzed included prognosis and diagnosis (determined by clinician judgment, HLH 2004 criteria with a four variable threshold and HScore).

Results: Among 123 included patients, 30 met HLH-2004 criteria, corresponding to a prevalence of 0.42% of ICU admissions, likely underestimated. Their 28-day mortality rate was 46.7%; their 1-year mortality rate was 75%. In the entire cohort, absence of infection as a trigger and higher SAPS II scores were independently associated with 28-day mortality in multivariate analysis. Diagnostic concordance was 69.1% with the HScore, 61.8% with clinician judgment, and 71.5% with the four-variable HLH-2004 threshold, yielding an overall agreement of 46.3%.

Conclusion: Our study describes a population of adults suspected of HLH in the ICU. Improved diagnostic strategies are needed to facilitate timely recognition and optimize patient outcomes.

Therapeutic options for newly diagnosed (ND) acute myeloid leukemia (AML) have increased in recent years, leading to a shift in the treatment paradigm from conventional, intensive chemotherapy toward targeted and less intensive therapy. Since 2017, there has been a surge in FDA approvals for novel therapies, including small molecule inhibitors and new combinations of chemotherapy and targeted drugs. It is unclear what effect these changes have had on overall survival in the real-world clinical setting over time. We retrospectively analyzed 501 patients with ND AML treated at an urban academic cancer center from 2015 to 2022 with respect to survival rates and treatment regimen utilization trends over time, in the context of AML risk category and whether allogeneic stem cell transplantation (HSCT) occurred. Among European LeukemiaNet 2022 intermediate risk ND AML patients who did not undergo HSCT, overall survival and relapse-free survival improved significantly in the early versus later cohort (2015-2018 vs. 2019-2022, respectively). These gains were not observed in the adverse-risk subgroup, where outcomes remain unchanged. First-line use of hypomethylating agent-based therapies increased seven-fold, while reliance on chemotherapy alone decreased by half. These findings highlight a meaningful shift in treatment patterns associated with improved outcomes overall, but an ongoing lack of progress in the highest-risk subgroups.

Objectives: To evaluate the efficacy and safety of venetoclax combined with intensive chemotherapy regimens in patients with relapsed or refractory acute myeloid leukemia (R/R AML) through a systematic review and single-arm meta-analysis.

Methods: A systematic search of PubMed, Embase, and Cochrane CENTRAL was conducted from inception to January 2025. Non-randomized studies enrolling R/R AML patients treated with venetoclax plus intensive chemotherapy were included. Pooled rates of complete remission (CR), composite complete remission (CRc), overall response rate (ORR), and adverse events were estimated using random-effects models. Heterogeneity was assessed with I² statistics, and sensitivity and subgroup analyses were performed according to chemotherapy regimen.

Results: Six retrospective studies comprising 235 patients were included. The pooled CR rate was 27.0% (95% CI, 9.18-57.50; I² = 84.6%), CRc rate was 51.45% (95% CI, 36.15-66.76; I² = 83.5%), and ORR was 63.79% (95% CI, 49.67-77.92; I² = 82.0%). Febrile neutropenia occurred in 71.38% and pneumonia in 23.6% of patients.

Conclusions: Venetoclax combined with intensive chemotherapy demonstrates meaningful antileukemic activity in R/R AML, with an expected toxicity profile. Prospective trials are warranted to define its role relative to standard salvage therapies.

Background: Secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome (sHLH/MAS) is a rare but highly fatal complication after allogeneic hematopoietic cell transplantation (allo-HCT), frequently diagnosed under conditions of clinical uncertainty. We aimed to characterize post-transplant sHLH/MAS and to identify clinically accessible factors associated with early mortality.

Methods: We retrospectively analyzed adult patients who developed sHLH/MAS after allo-HCT between 2018 and 2025. Inclusion required an HScore ≥ 169. Overall survival within 60 days from sHLH/MAS onset was the primary endpoint. Clinical and laboratory variables were evaluated using Cox proportional-hazards models, and patients were stratified according to the number of adverse prognostic factors identified.

Results: Seventy-two patients met inclusion criteria. Median time from allo-HCT to sHLH/MAS onset was 22 days. Sixty-day overall survival was poor. In univariable and multivariable analyses, vasopressor-dependent sepsis (HR 7.77, p < 0.001) and ferritin > 15 000 μg/L (HR 3.48, p = 0.002) were independently associated with early mortality. Stratification based on these two factors separated patients into low-, intermediate-, and high-risk groups with 60-day survival of 92%, 52%, and 9%, respectively (p < 0.001).

Conclusions: Post-transplant sHLH/MAS is associated with extremely high early mortality. Vasopressor-dependent sepsis and extreme hyperferritinemia identify patients at particularly high risk. These findings require confirmation in independent cohorts.

Aims: New therapies are improving outcomes even in advanced stages of multiple myeloma.

Objectives: To describe the experience of bispecific antibodies (BsAbs) in Mexico.

Results: The study included 41 patients with triple-class refractory (88%) and penta-drug refractory (61%) myeloma. The median number of prior treatment lines was 3, and the median time to response was 2 months. Step-up dosages were administered on an outpatient basis in 34 patients (83%). BsAbs were administered every 2 weeks to 19 patients (46%) and monthly to 17 patients (41.5%). Thirteen of these (31.5%) switched to monthly doses early in treatment and maintained their response. Twenty-five of 38 evaluated patients (66%) achieved a complete response or better, and 84% were negative for minimal residual disease. The median response duration was 10 months, while median progression-free survival and overall survival were 12 and 13 months, respectively. Extramedullary disease, no complete response, positivity for minimal residual disease, and penta-refractoriness were associated with poor outcomes. The adverse events were lower than those reported in clinical trials.

Conclusions: In conclusion, using outpatient step-up dosing followed by planned de-escalation to monthly doses of BsAbs in responding patients with MM is feasible, safe, and effective, and may improve access to this novel therapy.

Pediatric patients with hematologic and oncologic diseases often undergo surgical procedures as part of diagnosis and therapy. These include central venous catheter placements, tumor resections, lymph node and bone marrow biopsies, among others. Optimal postoperative care in this vulnerable population is critical, as children receiving chemotherapy or stem cell transplantation are immunocompromised and at high risk for infections, bleeding, and other complications. This review provides a comprehensive overview of common pediatric hemato-oncologic surgeries and detailed postoperative management strategies. A thorough, multidisciplinary postoperative plan is essential for pediatric hematology-oncology patients to minimize morbidity, avoid delays in adjuvant therapy, and ultimately enhance survival and quality of life.