Expert Review of Hematology最新文献

Introduction: Hodgkin lymphoma (HL) is a curable disease; however, 10-20% of patients experience relapsed/refractory disease. While autologous hematopoietic cell transplantation (auto-HCT) remains standard, a substantial proportion relapse, necessitating alternative strategies. Allogeneic HCT (allo-HCT) remains a potentially curative option and here we emphasize the role of reduced-intensity conditioning (RIC) in HL.

Areas covered: In this review, we compare the feasibility, efficacy, and safety of myeloablative conditioning (MAC) and RIC allo-HCT in relapsed/refractory HL. Additionally, we describe the evolving landscape of transplantation in HL with the use of novel agents, especially immune checkpoint inhibitors, the role of alternative donors especially for ethnic minorities, and the evolving literature on the role of post-transplant Cyclophosphamide (PTC) in improving outcomes.

Expert opinion: Allo-HCT remains a potentially curative option for patients with relapsed/refractory HL. RIC allo-HCT has emerged as the preferred platform for most patients, offering a favorable balance between efficacy and tolerability by leveraging graft-versus-malignancy (GVM) effects while minimizing non-relapse mortality over myeloablative conditioning. The use of ICI in the first line has significantly altered post-transplant outcomes by enhancing GVM effects but also increasing the risk of graft-versus-host disease (GVHD). PTCy-based prophylaxis and optimized donor selection now enable the safer use of alternative donors without compromising outcomes.

Background: Mesenchymal stromal cells (MSCs) have emerged as a potential alternative therapeutic strategy for the prophylaxis of graft-versus-host disease (GVHD) in patients undergoing hematopoietic stem cell transplantation (HSCT).

Research design and methods: This meta-analysis included eight randomized controlled trials (RCTs) involving 570 patients. The primary outcomes assessed were overall survival (OS), the development of acute GVHD(aGVHD), and chronic GVHD (cGVHD). The statistical analysis was performed using Review Manager (RevMan 5.4) with a random-effects model.

Results: The meta-analysis showed a significant improvement in overall survival in the MSC group compared to the control group (RR 1.12; 95% CI: 1.02-1.23), with no evidence of heterogeneity (I² = 0%). MSC prophylaxis was associated with a significant reduction in the incidence of aGVHD (RR 0.67; 95% CI: 0.40-0.83) and cGVHD (RR 0.65; 95% CI: 0.49-0.87). However, no significant difference was found between the MSC and control groups regarding primary disease relapse (RR 1.00; 95% CI:0.73-1.38) or the incidence of infections (RR 0.80; 95% CI:0.57-1.11). In terms of patients with at least one adverse event, no statistically significant difference was observed between the two groups (RR 1.10; 95% CI: 0.74-1.63).

Conclusions: MSC prophylaxis significantly improves overall survival and reduces the incidence of both aGVHD and cGVHD in HSCT patients, without increasing the risk of relapse, infections, or adverse events, indicating its potential as a safe and effective intervention for GVHD management. Further large-scale, multicenter RCTs are needed to validate or refute the current findings.

Registration: This review has been registered with theInternational Prospective Register of Systematic Reviews (PROSPERO)(CRD42024569358).

Background: Cytogenetic tests are essential prognostic indicators for patients diagnosed with multiple myeloma (MM). The study aimed to evaluate the prevalence of cytogenetic abnormalities and their prognostic significance in patients with newly diagnosed MM.

Research design and methods: A cohort study involving 88 cases. Malignant plasma cells were isolated, and interphase fluorescent in situ hybridization was performed on bone marrow samples.

Results: The gain of 1q was observed in 17 (19%) patients, followed by t(4;14) in 10 (11.5%), and the 17p or P53 mutation was found in only 6 (7%) patients. Three patients (3.5%) exhibited t(14;16). Amplification of 1q was not detected in any of the samples. The presence of t(4;14), anemia, renal disease, a revised myeloma comorbidity index (R-MCI) of 7-9, and a lack of treatment response were associated with poor progression-free survival. Additionally, t(4;14), anemia, elevated LDH, an R-MCI of 7-9, and absence of maintenance treatment correlated with decreased overall survival. In the Cox regression analysis, the presence of t(4;14) and an R-MCI of 7-9 were the most significant factors predicting worse outcomes.

Conclusions: The t(4;14) and RMCI are reliable predictors of poor survival in newly diagnosed MM patients.

Introduction: Hemophilia A and B are lifelong bleeding disorders traditionally managed with factor replacement therapy. While effective, this approach is limited by frequent infusions, inhibitor development, and high treatment costs, underscoring the need for innovative therapies that improve patient outcomes and quality of life.

Areas covered: This review explores recent advances in hemophilia management, focusing on extended half-life factor concentrates, non-factor therapies, such as bispecific antibodies and rebalancing agents, and the emergence of gene therapy as a potential functional cure. English-language studies on hemophilia therapies were searched in PubMed, Embase, Web of Science, and ClinicalTrials.gov (Jan 2014 to Apr 2025). A comprehensive literature review was conducted, covering pivotal clinical trials, real-world data, and translational research addressing both efficacy and safety considerations.

Expert opinion: Innovative therapies are transforming hemophilia care, offering simplified administration, superior bleed prevention, and new hope for patients with inhibitors. Gene therapies mark a milestone, but present challenges related to durability, immune response, and cost. Personalized treatment strategies, integrating patient-specific factors and shared decision-making, are essential to optimizing outcomes. Continued research, long-term surveillance, and efforts to improve global access will define the next era of hemophilia management, moving closer to a future where patients can lead lives free from the burden of bleeding.

Background: LINC00652 plays pivotal roles in acute lymphoblastic leukemia (ALL) a heterogeneous hematological malignancy. Here, we investigated the potential regulatory mechanisms of LINC00652 in ALL.

Research design and methods: Genome-wide association study data for LINC00652 were obtained for Mendelian randomization and integrated with RNA sequencing data, Bioinformatics analyses, including weighted gene co-expression network analysis (WGCNA), Spearman or Pearson correlation analysis, function, immune microenvironment, subcellular localization, and competing endogenous RNA (ceRNA) network construction, were employed explore the potential mechanisms of LINC00652 in ALL.

Results: LINC00652 exhibited no significant causal relationship with ALL but was identified as a protective factor (p > 0.05). LINC00652 levels were significantly decreased in patients with ALL, while WGCNA demonstrated the significance of black and blue modules for ALL. Seventy-nine messenger RNA (mRNAs) (SYT7) significantly correlated with LINC00652 (p > 0.05) and were enriched in the Janus kinase/signal transducer and activator of transcription (STAT), interleukin 2-STAT5, apoptosis, and adipogenesis pathways. Twenty-eight immune cells infiltrated the ALL, with immature B-cells and gamma delta T-cells significantly associated with LINC00652 expression (p < 0.05). LINC00652 was predominantly cytoplasmic, and a ceRNA network involving LINC00652, 36 microRNAs, and 18 mRNAs were proposed.

Conclusions: LINC00652 May protect against ALL and influence its pathogenesis through ceRNA mechanisms.

Background: Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) result from clonal proliferation of hematopoietic stem cells, and include polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Key driver mutations in the JAK2, CALR, and MPL genes are important for diagnosis and differentiation of triple-negative cases. The MPL gene, particularly exon 10, harbors mutation hotspots influencing pathogenesis and prognosis.

Research design and methods: This study presents two cases of atypical MPL mutations in MPN-patients and investigates the prevalence of non-canonical MPL mutations in the literature.

Results: We report two MPN cases with non-canonical MPL mutations (S204P and W515R) detected by next-generation sequencing. We also conducted a systematic review of the PubMed database, identifying 67 cases of non-W515L/K MPL mutations. A total of 84 mutations were identified, comprised of 30 unique non-canonical mutations. W515R/S/A were the most frequent (32%), followed by V501A/M (15%) and S505N/C (13%). About 58% of patients had ET, 25% PMF and 13% post-ET/PV MF. Most mutations (69%) occurred in exon 10. About 26% harbored concurrent JAK2, CALR and MPL mutations.

Conclusions: Our findings highlight the importance of non-canonical mutations in diagnosis of MPN to prevent misclassification and improve patient management. Understanding these mutations may lead to more tailored treatments and better outcomes in MPN patients.

Introduction: Chronic myeloid leukemia (CML) is a disease characterized by a single diagnostic molecular abnormality and epitomizes a genetically based diagnosis and management. Targeted therapy with tyrosine kinase inhibitors has revolutionized treatment and prognosis of this disease; however, a proportion of patients will experience resistance to therapy and progress to blast phase, the terminal phase of this disease. Emerging genomic profiling in CML reveals a genetically heterogenous landscape which may permit further risk stratification, personalization of treatment, and the potential for drug development.This review encompasses original literature exploring the genomic profile of CML and the potential impact of additional genomic abnormalities on prognosis and treatment response.

Expert opinion: Somatic variants in cancer-associated genes, particularly ASXL1, are of prognostic and potential therapeutic significance in CML. Up-front next-generation sequencing is therefore useful when available in all patients with newly diagnosed CML and repeat testing should be considered at timepoints of suboptimal treatment response, TKI resistance, and progression. Gene rearrangements and fusions are an emerging class of mutation that may confer adverse prognostic risk and hence use of a robust testing method that enables detection of such abnormalities is desirable.

Background: The association between sickle cell disease (SCD) and autoimmune diseases (AID) is not well understood. This retrospective study aims to investigate the frequency of coexistence of AIDS with SCD.

Research design and methods: This study was conducted in a tertiary care hospital. Data of n = 168 SCD patients between January 2016 and March 2023 were extracted and analyzed. Data included demographics, medications, hospitalization, phenotypes, presence of AIDs, and laboratory data.

Results: The mean age of n = 168 SCD patients was 30.66 (SD ± 11.27), with 54.2% of cases being female. Overall, 88.56% of patients had HGBSS phenotyping. The incidence of SCD cases with negative AID was 84.52%, while incidence of SCD cases with positive AID was 15.47% (p = 0.00001). Systemic lupus erythematosus (SLE, 4.2%), hypothyroidism (3.6%), and antiphospholipid syndrome (APS, 3.6%) were the most common SCD-associated AIDs. In addition, 69.2% of AIDs-positive patients used hydroxyurea. A strong correlation was found between hospitalization rate and a positive AID (p = 0.03).

Conclusions: The result of this study represents the significant rate of AID and SCD coexistence. The findings require further study to substantiate the need to develop recommendations for screening and early detection of the SCD-associated AIDs.

Background: Timely hemostatic therapy is essential when persons with hemophilia (PwH) present to the emergency department (ED), with guidelines recommending treatment at the time a bleed is suspected ('Factor First' strategy).

Research design and methods: This study examined ED management of PwH in Southern Alberta from 2014 to 2022, focusing on adherence to guidelines.

Results: A total of 393 ED visits from 191 adults with hemophilia A or B were identified. Most visits (86%) required emergent or urgent care. Median times from ED registration to ordering and administering hemostatic therapy were 2.9 and 4.2 hours, respectively, with treatment given within 2 hours in a minority of cases. Laboratory tests were ordered in nearly half of visits, with a median ordering time of 65 minutes. Use of individualized emergency management protocols increased over time, reaching 91.4% in 2022. Median ED stay was 3.4 hours, and approximately 25% of visits had a hemophilia-related admission diagnosis.

Conclusions: These findings highlight persistent delays and nonadherence to best practice recommendations, emphasizing the need for targeted quality improvement interventions to ensure timely, guideline-concordant care for PwH in emergency settings.