Expert Review of Hematology最新文献

Introduction: The optimal conditioning regimen prior to autologous stem cell transplantation (Auto-HSCT) in multiple myeloma remains uncertain. We conducted a systematic review and meta-analysis to compare the efficacy and safety of busulfan-melphalan (BUMEL) versus high-dose melphalan (HDMEL) conditioning.

Methods: A systematic literature search of PubMed, Embase, and the Cochrane Library was performed to from inception to 15 April 2025 to identify comparative studies evaluating BUMEL and HDMEL conditioning prior to Auto-HSCT. Eligible studies reported efficacy and/or safety outcomes. Risk of bias was assessed using standard methodological criteria. Pooled hazard ratios and odds ratios with 95% confidence intervals were calculated using random-effects models.

Results: Eleven studies comprising transplant-eligible patients with multiple myeloma were included. BUMEL conditioning was associated with improved progression-free survival compared with HDMEL, favoring BUMEL (HR: 0.83, 95% CI: 0.76-0.89, p < 0.00001), while no definitive overall survival benefit was observed HR: 1.10, 95% CI: 1.00-1.21, p = 0.05). BUMEL was associated with higher rates of mucositis, infections, and hepatic toxicity.

Conclusions: BUMEL conditioning offers improved disease control at the cost of increased toxicity, without a clear overall survival advantage. These findings support individualized conditioning selection, particularly in settings where upfront ASCT remains standard practice.

Registration: This protocol was registered on PROSPERO with an ID of CRD420261292372.

Introduction: High-dose methotrexate (HDMTX) is an important therapeutic tool for various malignancies; its use can be associated with severe treatment-emergent toxicities, particularly nephrotoxicity. These can disrupt anticancer treatment and increase morbidity and mortality. Glucarpidase (carboxypeptidase G2), a recombinant bacterial enzyme, rapidly converts toxic levels of circulating methotrexate (MTX) into nontoxic metabolites in patients with delayed MTX elimination and/or at risk of MTX toxicity. The reduction in MTX-associated toxicity and mortality can improve patients' outcomes. MTX elimination prevents the progression of renal toxicity and may minimize treatment disruptions by facilitating resumption of anticancer treatment, including HDMTX rechallenge. Currently, glucarpidase is underused in clinical practice, partly due to accessibility issues and uncertainty regarding treatment timings.

Areas covered: This review aims to provide clarity into the optimal application of glucarpidase by exploring its history and development, reviewing the clinical benefits reported in clinical trials and from real-world experiences, and critically considering recommendations for its administration.

Expert opinion: Glucarpidase is an invaluable tool in the management of MTX toxicity, allowing rapid and effective reduction of MTX toxic drug levels, especially in patients with compromised renal function. To update glucarpidase administration algorithms, research is needed to evaluate its efficacy in patients with moderate MTX elevations.

Introduction: Targeted therapies have improved both efficacy and safety profiles in chronic lymphocytic leukemia (CLL). Nevertheless, they present novel challenges in patient selection, particularly within aging populations wherein individuals aged over 80 years remain underrepresented in clinical trials.This review examines how frailty and biological aging intersect with CLL to inform risk stratification, treatment decisions, and supportive care.

Areas covered: We conducted a systematic literature search of PubMed and MEDLINE to identify studies including frail patients with CLL. Key findings indicate that frailty affects approximately 20% of patients with CLL. Alongside preexisting comorbidities, pre-malignant aging processes - such as clonal hematopoiesis of indeterminate potential (CHIP) and monoclonal B-cell lymphocytosis (MBL) - contribute to an underlying frailty predisposition, which is exacerbated by CLL and its treatments through cytopenias, heightened infection risk, and organ dysfunction. Comprehensive geriatric assessment (CGA) remains the gold standard for frailty evaluation, yet its implementation in routine clinical practice is limited by time constraints and resource demands. Pragmatic screening tools, including the Clinical Frailty Scale (CFS), Geriatric 8 (G8), and Fried Frailty Phenotype, facilitate feasible risk stratification. As frailty represents a dynamic state, initial assessments should be augmented by serial monitoring to inform adjustments in therapeutic intensity and supportive care.

Expert opinion: Personalized therapy planning that optimizes efficacy while mitigating toxicity in elderly/frail patients should be pursued. Future trials should ideally compare fixed-duration versus continuous therapy in well-characterized older or frail cohorts, with explicit objectives to enhance real-world applicability.

Introduction: Complement homeostasis is essential for healthy pregnancy and excessive complement activation can lead to devastating maternal and fetal outcomes by precipitating or worsening complement-mediated disorders. This review summarizes changes in complement regulation during pregnancy, management considerations in paroxysmal nocturnal hemoglobinuria (PNH), thrombotic microangiopathies (TMA), and antiphospholipid syndrome (APS), and emerging evidence regarding the role of complement in the severe hypertensive disorders of pregnancy (preeclampsia with severe features, HELLP syndrome).

Areas covered: This is an expert narrative review. Articles were selected based on the authors' subject-matter expertise to highlight key studies, concepts, and areas of active investigation, rather than through a systematic literature search strategy. Relevant articles on the role of complement in pregnancy are summarized and critiqued. We review pregnancy outcomes and management in PNH, TMA, and APS. We prioritize review of clinical trials, registry or systematic review studies, and novel case reports utilizing complement inhibitors during pregnancy.

Expert opinion: Complement inhibitors have greatly improved maternal morbidity and mortality in PNH and complement-mediated TMAs. Establishing functional biomarkers of complement activity in pregnancy, defining metrics for prompt use of complement inhibitors in TMAs, and clinical trials of complement inhibition for obstetric APS and hypertensive disorders of pregnancy are urgently needed.

Introduction: Air pollution and household fuel use may impair hematologic health through inflammation and oxidative stress. We synthesized evidence on associations of ambient/household air pollution with anemia risk and erythrocyte indices.

Methods: We searched PubMed, Embase, and Web of Science (inception-27 September 2025). Two reviewers independently screened and extracted data, and assessed risk of bias using Joanna Briggs Institute checklists. Random-effects meta-analyses pooled risk ratios (RRs) per 10 µg/m³ for particulate matter with aerodynamic diameter ≤10 µm (PM₁₀), ≤2.5 µm (PM_2.5), and nitrogen dioxide (NO₂), and by household fuel type.

Results: Thirty-six studies were included. Each 10 µg/m³ increase in PM_2.5 and NO₂ was associated with higher anemia risk (RR 1.200, 95% CI 1.041-1.384, I² 98.2%; RR 1.127, 95% CI 1.025-1.241, I² 98.0%). Solid and biomass fuel increased anemia risk (RR 1.143, 95% CI 1.027-1.274, I² 82.9%; RR 1.271, 95% CI 1.050-1.539, I² 91.7%). PM₁₀ was associated with lower hemoglobin (0.074 g/dL, 95% CI -0.124 to -0.023, I² 90.7%). Effects were generally stronger in males and in low- and middle-income countries.

Conclusions: Ambient and household air pollution are associated with increased anemia risk and reductions in hemoglobin; high heterogeneity and observational designs limit causal inference.

Background: This study challenges the static and linear assumptions of traditional prognostic models for diffuse large B-cell lymphoma (DLBCL), such as the International Prognostic Index (IPI).

Research design and methods: Analyzing 664 DLBCL patients treated with R-CHOP, the research explored the time-dependent and nonlinear effects of established risk factors.

Results: While the IPI maintained strong overall prognostic stability, its individual components exhibited dynamic behavior. ECOG performance score, beta-2 microglobulin (β2 M), and lactate dehydrogenase (LDH) were key predictors of early mortality, with their influence diminishing over time. Conversely, the importance of Ann Arbor stage and extranodal involvement grew, identifying them as markers of later risk. Notably, the study found a resurgence in the predictive power of β2 M after two years. Furthermore, restricted cubic spline modeling revealed significant nonlinear relationships between overall survival and age, LDH, and β2 M (all p < 0.001 for nonlinearity).

Conclusions: The prognostic impact of baseline factors in DLBCL follows dynamic and nonlinear trajectories, challenging the one-size-fits-all approach of current risk scores. Future models should incorporate these temporal dynamics to provide a more accurate, personalized risk assessment.

Background: Hemato-oncological diseases have been described as a common cause of secondary immune thrombocytopenia (ITP). So far, studies on patients with active hemato-oncological disease and concurrent ITP are limited, making it difficult to provide clear treatment recommendations. Due to the underlying disease and cancer treatment, this patient population is especially vulnerable.

Research design and methods: This retrospective, single-center pilot study investigated treatment response and time-to-treatment response in patients with newly diagnosed ITP, comparing those with active hemato-oncological disease, those in remission after malignancy, to those without any underlying malignancy.

Results: Comparable response rates to ITP treatment were observed across these groups, including the achievement of platelet counts above 30 G/L and complete response (platelet counts ≥100 G/L). However, patients with an active hematologic-oncological malignancy exhibited a significantly longer time to platelet recovery after initiating steroid therapy.

Conclusion: Our preliminary data suggest that standard treatment recommendations for primary ITP may be effective in patients with an active hematologic - oncologic malignancy. However, therapy responses could be significantly delayed, warranting closer monitoring. Given the pilot nature of this study and the limited sample size, these findings should be considered hypothesis-generating and require confirmation in larger studies.

Introduction: Despite advances in the treatment of multiple myeloma (MM), there remains a significant need for new modalities, mechanisms of action (MOA), and combinations to achieve durable remissions. Bispecific T-cell engagers (BiTEs), particularly those targeting B-cell maturation antigen (BCMA), have demonstrated robust outcomes in patients with progression through multiple lines of therapy. Linvoseltamab, a novel BCMAxCD3 bispecific, was recently the FDA and EMA-approved based on the LINKER-MM1 trial for the treatment of patients with relapsed or refractory multiple myeloma (RRMM) who have progressed beyond four lines of therapy.

Areas covered: We will discuss the MOA, pharmacokinetics, efficacy, and toxicity of linvoseltamab compared with other approved BiTEs. We will highlight linvoseltamab's patient-centric dosing regimen and improved side effect profile, and we will review published indirect efficacy comparisons with other approved BCMA directed therapies.

Expert opinion: Linvoseltamab is the fourth FDA approved bispecific antibody for the treatment of RRMM in patients who have received four or more lines of therapy. Cross-trial comparisons ave suggested that linvoseltamab has comparable to slightly better efficacy compared with other agents. Linvoseltamab offers an optimized dosing regimen with a favorable CRS profile. Further real-world data are needed to understand linvoseltamab's role within the MM treatment paradigm.

Introduction: Faced with a shortage of blood sources, clinicians have been striving to utilize blood judiciously for critically ill patients. Although some researchers have attempted to explore this issue, there is still no consensus on its applicability in different situations. Therefore, we first conducted a systematic review and meta-analysis by category, providing a more scientific and reasonable basis for clinical treatment decisions.

Methods: We searched databases up to 11 June 2025, including PubMed, EmBase, Cochrane, and Web of Science. The participants were critically ill adult patients. We collected and grouped different hemoglobin (Hb) thresholds during restricted and liberal blood transfusions. The primary outcomes encompassed mortality rate, length of hospital stay, and adverse reactions.

Results: 30,943 critically ill patients were included in 33 studies. Patients with closed head injuries in the restricted group had a higher risk of mortality (RR = 1.78, 95% CI: 1.48-2.15), particularly those with concomitant subarachnoid hemorrhage; Mortality rates were also higher among cardiovascular patients over the age of 60 (RR = 1.54, 95% CI = 1.05-2.24); Tertiary hospitals were found to facilitate patient recovery.

Conclusions: Critical patients with closed brain injuries and comorbidities, as well as those over 60 years old with cardiovascular diseases, may benefit from high-threshold liberal strategies. The protocol was registered on PROSPERO with the ID of CRD42024606971.