Expert Review of Hematology最新文献

Background: The recent discontinuation of antihemophilic factor Method M, monoclonally purified (AHF-M) and recombinant antihemophilic factor (rAHF) requires evaluation of hemophilia A treatment strategies for some patients. This post-hoc analysis characterized the safety and efficacy of third-generation recombinant factor VIII (FVIII) products (antihemophilic factor [recombinant], plasma/albumin-free method [rAHF-PFM] and PEGylated rAHF [rAHF-PEG]) after switching from plasma-derived AHF-M or first-generation rAHF.

Research design and methods: Previously treated patients from three trials (rAHF-PFM: two; rAHF-PEG: one) whose last recorded FVIII replacement therapy was either AHF-M or rAHF were included. Bleeding outcomes, consumption, hemostatic efficacy, safety, and immunogenicity were evaluated.

Results: Of 114 participants, 19 were previously treated with AHF-M and 95 with rAHF; 97 participants transitioned to rAHF-PFM and 17 to rAHF-PEG. Participants switching to rAHF-PEG prophylaxis achieved lower bleeding rates compared with previous prophylaxis. Most bleeding events were treated with one to two infusions of rAHF-PFM or rAHF-PEG with good or excellent hemostatic efficacy ratings. No participants developed inhibitors to rAHF-PFM or rAHF-PEG.

Conclusions: Results from this post-hoc analysis demonstrated improvements in bleeding outcomes in participants switching to rAHF-PEG and were consistent with the original trial results, supporting the feasibility of transitioning from the older- to newer-generation Takeda FVIII replacement therapies.

Introduction: Undetectable minimal residual disease (uMRD) has emerged as a critical prognostic and potentially predictive biomarker in chronic lymphocytic leukemia (CLL), particularly in venetoclax-based time-limited regimens.

Areas covered: Clinical trials such as MURANO, CLL-14, and CLL-13 have shown that uMRD at the end of treatment correlates with prolonged progression-free survival (PFS) and overall survival (OS), irrespective of disease biology. MRD-adapted strategies in BTK inhibitor + venetoclax combinations have also been explored, with studies suggesting that MRD-adapted therapy results in durable remissions and potential for reduced toxicity. Recent studies have begun to explore MRD-guided therapy duration for venetoclax + anti-CD20 monoclonal antibody regimens, allowing for tailored treatment based on the depth of response. In this review, we highlight that the predictive value of MRD appears to be regimen- and biology-specific, with differing implications for patients with mutated versus unmutated IGHV.

Expert opinion: While fixed-duration therapy simplifies treatment, MRD-guided approaches offer a more individualized strategy that may optimize outcomes while minimizing overtreatment. Ongoing trials will further define the role of MRD-adapted therapy duration in first-line CLL treatment. Overall, MRD is a powerful tool to move beyond one-size-fits-all regimens and may become integral in personalizing CLL management across diverse therapeutic regimens.

Introduction: Allogeneic hematopoietic cell transplantation (allo-HCT) remains the only available curative treatment option for hematologic manifestations of Fanconi Anemia (FA), which include bone marrow failure and hematological malignancies. Outcomes after allo-HCT have improved significantly over the last 30 years by optimizing preparative regimens, graft-versus-host-disease (GvHD) prophylaxis and supportive care. Nevertheless, indications for transplant should be carefully weighed, based on a thorough evaluation of risks and benefits, as this procedure has intrinsic morbidity and mortality and may increase the risk and accelerate the onset of late malignancies and FA related complications.This review, following a thorough Medline search of the pertinent published studies, reports the most recent data on HCT in FA, focusing on HCT strategies, post-transplant follow-up, and impact of allo-HCT on FA-associated late effects.

Expert opinion: While we continue to generate evidence to determine the optimal candidates, timing and strategies for HCT in FA patients, we must also consider the implications for future treatment modalities like gene therapy/gene editing. The primary objective of all strategies must be to mitigate - or at the very least, not exacerbate - the risk of long-term complications that remain a leading cause of the unacceptably high mortality rate in FA.

Background: A comprehensive quantitative analysis was conducted to examine patient preferences for chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) treatment attributes.

Research design and methods: A discrete choice experiment survey was conducted in United States patients with CLL/SLL. Treatment attributes (efficacy, safety, convenience) were identified through literature review and clinical input. Attributes' relative importance and patients' willingness to trade off attributes were calculated using conditional logistic regression.

Results: Among 200 respondents, attributes with the highest to the lowest importance were impact of atrial fibrillation on quality of life (QoL; 23.9%); progression-free survival (PFS; 18.6%); impacts of headache (17.7%), diarrhea (14.3%), hypertension (13.6%) on QoL; dosing frequency (8.8%); and formulation type (3.1%). Patients preferred treatments with higher efficacy, less impact of AEs on QoL, lower dosing frequency, and tablets over capsules (p < 0.05). Patients were willing to trade off 2.57 and 1.91 years of PFS for less impact of atrial fibrillation and headache on QoL, respectively.

Conclusions: Findings suggest that among treatment attributes assessed, the most important attributes for CLL/SLL patients were impact of atrial fibrillation on QoL, PFS, and impact of headache on QoL. Shared decision-making in treatment selection should include informed discussion about efficacy and impact of AEs on QoL.

Introduction: Allogeneic hematopoietic cell transplantation (allo-HCT) constitutes the only curative option for patients with hematological malignancies. Nevertheless, older or comorbid allo-HCT recipients are at greater risk for several allo-HCT-related complications. Treosulfan has emerged as an optimal part of prior HCT conditioning regimens in this patient population.

Areas covered: We summarize the clinical outcomes of older/frail patients treated with treosulfan-based regimens and, based on the pharmacological properties of treosulfan and the data derived from clinical studies, provide some insights regarding the rigorous clinical evaluation of patients in everyday clinical practice.

Expert opinion: Treosulfan is a safe and effective agent for conditioning in older or comorbid allo-HCT recipients, exhibiting comparable or superior survival outcomes compared to reduced intensity regimens and busulfan, with similar or lower rates of graft-versus-host disease and reduced non-relapse mortality. Before allo-HCT, geriatric assessment and evaluation of the underlying comorbidities are important for the selection of a personalized conditioning regimen.

Introduction: Large granular lymphocytic leukemia (LGLL) is a rare lymphoproliferative disease characterized by marked phenotypic, molecular, and clinical heterogeneity. Recent therapeutic advances and emerging clinical data warrant a comprehensive overview of current and evolving treatment strategies.

Areas covered: This review summarizes current and future therapeutic approaches in LGLL, including criteria for treatment initiation and response assessment. The literature was identified through a comprehensive search of PubMed up to November 2025. We address the evolving positions of the three main immunosuppressive agents - methotrexate, cyclophosphamide and ciclosporin A - along with other strategies such as chemotherapy, immunotherapy, and hematopoietic stem cell transplantation. In addition, we highlight emerging targeted therapies driven by advances in the understanding of LGLL pathophysiology. Ongoing clinical trials registered on ClinicalTrials.gov and novel agents likely to expand the therapeutic landscape of LGLL are also discussed.

Expert opinion: LGLL management is undergoing a paradigm shift with the emergence of multiple targeted therapeutic approaches. Future progress will depend on better prognostic stratification, better integration of disease and patient heterogeneity, and the development of personalized treatment strategies, potentially supported by molecular monitoring.

Introduction: Mantle cell lymphoma (MCL) represents a distinct subtype of mature B-cell lymphoma, considered incurable with a pattern of recurrent relapses and suboptimal responses to subsequent therapies that portends poorer prognosis with each recrudescent disease.

Areas covered: Covalent and non-covalent Bruton tyrosine kinase inhibitors (BTKi) have transformed the relapsed/refractory (R/R) MCL landscape as monotherapy but may emerge to be more effective as combinations with B-cell lymphoma-2 (BCL-2) inhibitors and immunotherapy. Immune-leveraging therapies, including chimeric antigen receptor (CAR) T-cell therapy and T-cell engaging antibodies are gaining momentum, with the former demonstrating durable responses in a subset of patients while the latter being evaluated in various combination regimens. Allogeneic hematopoietic stem cell transplants remain a potentially curative option for selected patients.

Expert opinion: This review seeks to navigate this increasingly complex therapeutic landscape while providing a suggested treatment and sequencing algorithm that may be tailored to individual patients.

Introduction: Chronic myeloid leukemia (CML) has been transformed by ATP-competitive BCR:ABL1 tyrosine kinase inhibitors (TKIs); however, resistance, intolerance, and long-term toxicity remain clinically relevant challenges, particularly in patients requiring prolonged therapy or multiple treatment lines. Asciminib, the first-in-class Specifically Targeting the ABL Myristoyl Pocket (STAMP) inhibitor, represents a paradigm shift by restoring physiologic ABL1 autoinhibition through allosteric binding.

Areas covered: This Special Report reviews the mechanistic basis, preclinical development, and clinical evidence supporting asciminib in CML. We summarize key data from pivotal trials, including ASCEMBL and ASC4FIRST, as well as emerging real-world studies, focusing on molecular response depth, safety, resistance mechanisms, and patient selection. Particular attention is paid to how STAMP inhibition differs from ATP-competitive TKIs in terms of selectivity, toxicity profile, and resistance patterns, and how asciminib can be positioned relative to ponatinib in later-line settings.

Expert opinion: Asciminib has established itself as an effective and generally well-tolerated option for patients with TKI-resistant or -intolerant CML and is poised to expand into earlier lines of therapy. Its ability to induce rapid and deep molecular responses with reduced off-target toxicity may have important implications for long-term disease control and future treatment-free remission (TFR) strategies. Ongoing studies will clarify its optimal sequencing, combination potential, and role in facilitating durable TFR.

Background: 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.

Research design and methods: We searched databases up to 11 June 2025, including PubMed, EmBase, Cochrane, and Web of Science. The participants were adult critically ill 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.

Background: Lymphoma poses a significant public health challenge with complex subtypes. While obesity and adipokines have been linked to lymphoma, causal relationships remain unclear. This study uses Mendelian randomization (MR) to systematically assess these associations.

Research design and methods: Two-sample MR analyzed genetic data from genome-wide association studies to evaluate causal links between obesity, adipokines (adiponectin, leptin, and resistin), and lymphoma subtypes (diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, Hodgkin lymphoma, and other unspecified types of non-Hodgkin lymphoma). Primary analysis used inverse variance weighted (IVW), supported by MR-Egger, weighted median, and weighted mode methods. Sensitivity analyses (MR-Egger regression, Cochran's Q test, MR-PRESSO, leave-one-out) and linkage disequilibrium score regression (LDSC) ensured robustness.

Results: IVW revealed obesity positively associated with follicular lymphoma (OR = 1.352, 95% CI: 1.095-1.670, p = 0.005) and other unspecified types of non-Hodgkin lymphoma (OR = 1.297, 95% CI: 1.050-1.603, p = 0.016). No significant links were found between adipokines and lymphoma. Sensitivity analyses confirmed no heterogeneity or pleiotropy.

Conclusions: Obesity may independently increase lymphoma risk, unrelated to adipokines. These findings highlight new risk factors, urging further research into pathological mechanisms and biomarkers.