Acta Haematologica最新文献

Objective: This study evaluated the prognostic role of circular RNAs (circRNAs) in individuals diagnosed with mantle cell lymphoma (MCL), using the framework of the competing endogenous RNA (ceRNA) network model.

Methods: Differentially expressed circRNAs were identified from the GSE159808 dataset, and differentially expressed messenger RNAs (mRNAs) were extracted from GSE32018. Corresponding microRNAs (miRNAs) were retrieved to construct a ceRNA regulatory network relevant to MCL. Functional enrichment analysis and survival analysis were performed on 35 mRNAs incorporated in the ceRNA network to identify transcripts associated with survival outcomes in MCL. A prognostically relevant ceRNA subnetwork was then constructed based on these results.

Results: Thirteen circRNAs (9 upregulated, 4 downregulated) and 457 differentially expressed mRNAs were identified. The initial ceRNA network included 11 circRNAs, 40 miRNAs, and 35 mRNAs. Gene Ontology analysis indicated enrichment in pathways related to dentin-containing tooth development, the plasma membrane signaling receptor complex, and growth factor receptor binding. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis demonstrated significant involvement in the B-cell receptor signaling pathway, Fc gamma receptor-mediated phagocytosis, and the Wnt signaling pathway. Survival analysis identified six mRNAs significantly associated with overall survival in individuals with MCL. These results were used to derive a refined prognostic ceRNA network consisting of 6 mRNAs, 7 miRNAs, and 6 circRNAs.

Conclusion: CircRNAs may regulate MCL prognosis by modulating miRNA-mRNA interactions within the ceRNA network. These findings suggest a regulatory mechanism by which circRNAs contribute to molecular pathways influencing disease progression and survival in MCL.

The gastro-intestinal (GI; gut) microbiota is important in the development and function of haematopoiesis. Abnormalities of the gut microbiota are termed dysbiosis which is associated with the development and prognosis of haematological disorders including clonal haematopoiesis of indeterminate potential (CHIP), leukaemias and plasma cell neoplasm (PCN). We review the role of the gut microbiota and dysbiosis in this context.

Introduction The Revised International Prognostic Scoring System (IPSS-R) has long been the standard prognostic tool in the management of myelodysplastic syndromes (MDS). Recently, a new clinical-molecular prognostic model, the IPSS-M, was introduced. This model integrates MDS-related gene mutations and offers improved accuracy and precision in predicting patient outcomes and survival. In this study, we compare the prognostic value and predictive capacity of these prognostic scores across different treatment groups. Methods IPSS, IPSS-R, and IPSS-M scores were calculated at diagnosis for all eligible MDS patients in this cohort. Sankey diagrams were generated to visually compare the risk stratification across the three scoring systems. Results A total of 394 patients were included in this retrospective analysis. During the course of the disease, 59.1% required treatment, with 38.1% (150 patients) receiving erythropoiesis-stimulating agents (ESA) and 19.0% (75 patients) treated with hypomethylating agents (HMA). The IPSS-M was calculated for 281 patients and reclassified 41.9% of cases: 20.3% (n=57) were upstaged and 21.7% (n=61) were downstaged. All three scoring systems demonstrated significant stratification of overall survival (OS) in the global cohort (p<0.001 for IPSS, IPSS-R, and IPSS-M). Notably, IPSS failed to predict OS in patients treated with azacitidine, and none of the scores successfully predicted OS in patients treated with ESA. Conclusion The IPSS-M effectively reclassified 41.9% of patients, upstaging 20.2% and downstaging 21.7%. However, our analysis found that none of the prognostic scores effectively predicted outcomes for ESA-treated patients. Further studies are needed to assess whether the predictive value of these scoring systems is influenced by the specific treatment modalities used.

Background: Chronic graft-versus-host disease (cGVHD) remains a major cause of late morbidity and non-relapse mortality following allogeneic hematopoietic cell transplantation. Early identification and intervention are critical to improving outcomes. Corticosteroids continue to serve as the first-line therapy; however, treatment-refractory cases are common and associated with poor outcomes. Ruxolitinib has become the standard second-line agent, yet beyond Ruxolitinib, treatment selection varies widely due to a lack of comparative data and standardized sequencing strategies.

Methods: A comprehensive review of key therapeutic trials in chronic GVHD was conducted, with a focus on second-line treatments and beyond. Emerging and investigational therapies were also included through analysis of recent literature and ongoing studies.

Results: There is currently no established sequencing of agents beyond second-line therapies. The approval of belumosudil, axatilimab, and ibrutinib has expanded therapeutic options, with each agent offering a unique mechanism of action and demonstrating promising, organ-specific response rates.

Conclusion: The therapeutic landscape for chronic GVHD is evolving, with several newer agents beginning to demonstrate utility in third-line settings. However, the selection of third-line agents remains largely dependent on clinical judgment, prior treatment history, and the specific organs involved. There is a continuing and critical need for well-designed, comparative trials to establish optimal treatment strategies.

Febrile neutropenia (FN) is a complication after autologous hematopoietic cell transplantation (auto-HCT). Although fluoroquinolone (FQ) prophylaxis can reduce FN rates, its use remains debated due to concerns about antimicrobial resistance. We retrospectively analyzed adult patients who underwent auto-HCT at A.C.Camargo Cancer Center between 2016 and 2021. Patients were grouped by FQ prophylaxis: those who received levofloxacin from 2016-2018 (Px group, n = 201) and those who did not from 2018-2021 (NPx group, n = 169). FN was more frequent in the NPx group (92%) than in the Px group (81%) (p = 0.002). However, no significant differences were found in microbiologically documented infections (23% vs. 14%, p = 0.09), 30-day mortality (3% vs. 1%, p = 0.25), or 100-day mortality (3% vs. 2%, p = 0.48). Resistance profiles differed: the Px group had fewer pan-susceptible isolates (17% vs. 61%) and higher rates of ESBL-producing organisms (27% vs. 6%) and methicillin-resistant bacteria (36% vs. 10%) (all p < 0.001). These findings indicate that although FQ prophylaxis reduces FN incidence, it does not affect short-term mortality and is associated with greater antimicrobial resistance. Based on these results, our institution does not recommend use of FQ prophylaxis in patients undergoing auto-HCT.

Background: Acute lymphoblastic leukaemia (ALL) is the commonest paediatric cancer and represents a fifth of adult leukaemias. Global outcome disparities are linked to variations in socio-demographic indices (SDIs). Summary: In high-SDI regions, established collaborative groups report cure rates surpassing 90% in paediatric ALL. The focus is on reducing treatment toxicity using chemotherapy-free strategies, principally T-cell-directed immunotherapies and targeted small molecules, as exemplified in adult Philadelphia-chromosome-positive ALL. High cure rates limit testing of novel approaches outside niche subgroups, while high costs preclude wider real-world adoption of these advances. Mid-SDI regions (50-80% cure) face challenges in fully implementing contemporary risk-adapted therapy to improve outcomes and reduce costs. This necessitates collaborative practice, standardised high-quality risk-stratification diagnostics, and access to quality-assured generic cytotoxics. Low-SDI regions (<50% cure) report rising disease burden and face more fundamental challenges, including timely diagnosis, access to treatment and expertise, and minimising toxicity and abandonment. Solutions require locally adapted protocols, collaborative partnerships, and sustained patient-support programmes. Key Message: Global partnerships across SDI regions are crucial to address shared challenges in ALL, including access to affordable quality therapeutics, continuing refinement of established treatment elements, tailoring biomarkers for diverse populations, and collaborative frameworks to evaluate new treatments, technologies, and treatment paradigms.

Background: The integration of novel antibody-mediated targeted therapies into both relapsed/refractory (R/R) and frontline pediatric acute lymphoblastic leukemia (ALL) treatment protocols has led to critical advancements in the field. Current research efforts focus on optimizing targeted therapies to enhance precision and efficacy while minimizing toxicity by reducing chemotherapy. A notable example is the addition of blinatumomab, demonstrating superiority over conventional chemotherapy, with an 8% increase in disease-free survival at an interim analysis, reaching 96%. Inotuzumab ozogamicin (InO) has also shown promise, achieving nearly a 70% complete response rate in pediatric R/R B-cell ALL (B-ALL) trials. Additionally, daratumumab in T-cell ALL (T-ALL) and chimeric antigen receptor T-cell therapies, particularly CD19-directed (B-ALL) and CD7-directed (T-ALL) strategies, are under active investigation.

Summary: This review will provide an overview of targeted antibody-mediated immunotherapies in both B-ALL and T-ALL, with a focus on their pediatric applications, supporting data, and future prospects.

Key messages: The next cycle of frontline trials in pediatric ALL will incorporate more immunotherapy with reduction of chemotherapy. Subsequent trials will utilize more concurrent chemoimmunotherapy blocks as precision testing and risk-adapted therapy will continue to develop. These advancements reflect a paradigm shift toward more precise, less toxic treatment strategies in pediatric ALL.

Background: Philadelphia chromosome-positive acute lymphoblastic leukemia has historically been associated with poor prognosis and limited therapeutic options. Over the past 2 decades, however, the treatment paradigm has markedly shifted.

Summary: The introduction of tyrosine kinase inhibitors (TKIs), such as imatinib, dasatinib, and ponatinib, has revolutionized frontline therapy, significantly improving remission rates and long-term survival. These agents, when combined with reduced-intensity chemotherapy or even with corticosteroids, have enabled less toxic regimens, particularly beneficial for older or unfit patients. The implementation of measurable residual disease monitoring has emerged as a pivotal tool for risk stratification and therapeutic decision-making. Consequently, the role of allogeneic hematopoietic stem cell transplantation, considered a cornerstone of curative treatment, is being reevaluated in patients achieving sustained deep molecular responses. More recently, immunotherapeutic strategies - including the bispecific T-cell engager blinatumomab and chimeric antigen receptor (CAR) T-cell therapies - have emerged as effective alternatives to conventional chemotherapy and TKIs.

Key messages: While TKIs remain the backbone of treatment, the integration of immunotherapeutic strategies - including bispecific antibodies and CAR T-cell therapy - has expanded therapeutic options, not only in the R/R setting but increasingly in frontline regimens. Ongoing research aimed at optimizing the sequencing, combination, and duration of these therapies is essential to further enhance clinical outcomes.

Background: Over the last 2 decades, significant improvements have been made in the understanding of the genomic and biological bases of acute lymphoblastic leukemia (ALL), resulting in enhanced genomic classification, more precise risk stratification, and improved long-term outcomes. ALL is a hematologic malignancy defined by uncontrolled proliferation of immature B- or T-lymphoid blasts in the bone marrow, blood, and other extramedullary tissues. It affects most commonly children, representing the most common childhood cancer, but it also occurs in adults where outcome tends to be poorer compared to pediatric patients.

Summary: A variety of genetic aberrations, including structural and numerical chromosome alterations, translocations generating fusion oncoproteins, cryptic genomic rearrangements, sequence mutations, and genomic copy number changes, define multiple genomic subtypes, influence risk stratification and determine response to therapeutic strategies.

Key messages: In this review, we describe the updated genomic classification of ALL highlighting new biological insights and discussing their implications for prognostication and outcome.