Expert Review of Hematology最新文献

Background: Pain is the most prevalent and debilitating symptom of sickle cell disease (SCD). However, there is a paucity of community-based, longitudinal data from low- and middle-income countries. This study is to systematically document phenotypic details of SCD-related pain in a cohort through a prospective, year-long study in underserved regions of five Indian states.

Research design and methods: Individuals with SCD were monitored prospectively for 24 fortnights. Pain-related data, including episode frequency, intensity, anatomical distribution, quality descriptors, and patterns, were collected. Statistical analyses comprised descriptive statistics, tests of significance and the Jonckheere - Terpstra trend test, etc.

Results: Across 6,048 visits to 252 patients, 2,042 pain episodes were reported, with 86.1% of patients experiencing at least one episode. Pain most frequently affected the lower legs and calves, with significantly higher rates among females (p < 0.001). Continuous and rhythmic pain patterns were associated with severe pain (p < 0.001). Sensory descriptors were more prevalent among high-intensity cases, suggesting neuropathic components.

Conclusion: This is the first Indian community-based longitudinal study revealing a significant prevalence of unreported pain and phenotypic variability. It contributes to the development of region-specific pain management frameworks by considering chronicity, gender, and sociocultural expressions of pain.

Objectives: To evaluate the effectiveness of PK-guided prophylaxis in severe hemophilia A.

Methods: 25 patients received PK-guided prophylaxis using a population PK tool (MyPKFiT), 30 received conventional fixed-dose prophylaxis. Outcomes over six months included bleeding frequency, joint health (HJHS), quality of life (SF-36), factor use, infusion frequency, costs, and adverse events.

Results: PK-guided group had fewer bleeds, improved HJHS and SF-36 scores, lower FVIII use, reduced infusions, and lower costs (all p<0.001).

Conclusion: PK-guided prophylaxis improves clinical outcomes and reduces costs, but the retrospective design and small sample size limit generalizability; further studies are needed for confirmation.

Introduction: Numerous risk staging systems exist for newly diagnosed multiple myeloma (NDMM), from older models which rely purely on markers of 'tumor burden' to modern scores which incorporate tumor genetics. While the 2025 IMS-IMWG high-risk criteria, based on specific cytogenetic analyses and the β2-microglobulin titer, represent a major push to harmonize NDMM risk stratification, multiple barriers to successful, comprehensive implementation in standard practice remain. There also exists substantial heterogeneity in how therapeutic trials quantify risk.

Areas covered: We herein summarize the novel 2025 IMS-IMWG criteria. We then provide a brief overview of the current state of NDMM risk stratification in standard practice, as well as the variability in 'high-risk' disease definitions in NDMM trials. Finally, we discuss ways in which such variation in 'high-risk' definition is being addressed.

Expert opinion: Attempts to improve prognostication and potentially demonstrate outcome prediction in NDMM have been confounded by variable performance of risk stratification in standard clinical practice and substantial heterogeneity of 'high-risk' definitions in clinical trials. If implemented comprehensively, the 2025 IMS-IMWG criteria will allow for apples-to-apples comparison across trials via meta-analysis and thus harmonize risk assessment in myeloma, setting the stage for investigation of risk-adapted treatment deescalation and intensification.

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.