Search Results (524)

Background and Clinical Significance: The COVID-19 pandemic led to the rapid development of effective vaccination strategies. Although COVID-19 vaccines are generally safe, rare hematological adverse events have been reported, most prominently vaccine-induced immune thrombotic thrombocytopenia (VITT). Isolated cases of autoimmune cytopenias and bone marrow failure syndromes following COVID-19 vaccination have also been described. Case Presentation: We report the case of an 80-year-old male who developed subacute-onset severe normocytic anemia with reticulocytopenia and mild leukopenia following heterologous COVID-19 vaccination with ChAdOx1 nCoV-19 (AstraZeneca) and BNT162b2 (Pfizer–BioNTech). Seven days after the second vaccination, mild anemia was detected, progressing over the following weeks to symptomatic anemia requiring hospitalization. Extensive diagnostic evaluation revealed no evidence of hemolysis, nutritional deficiency, autoimmune disease, or viral infection, including SARS-CoV-2 and Parvovirus B19. Bone marrow examination demonstrated an erythroid maturation arrest at the proerythroblast stage, resembling a pure red cell aplasia (PRCA)-like pattern. Cytogenetic and molecular analyses excluded myelodysplastic syndromes. Treatment with erythropoietin resulted in complete hematologic recovery. Conclusions: This case suggests that, in rare instances, COVID-19 vaccination may be temporally associated with transient suppression of erythropoiesis. Further studies are required to elucidate underlying mechanisms and to guide diagnosis and management. Full article

Background/Objectives: A complex karyotype (CK) in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDSs) is defined as the presence of three or more unrelated chromosomal abnormalities in the absence of defining core-binding factor translocations. Losses/Deletions on chromosomes 5, 7 and 17 are frequently observed. It is heavily associated with TP53 mutations, with 70–80% of CK cases in MDS/AML harboring TP53 mutations. Methods: An extensive literature search of the studies carried out in the last two decades has shown a consistent development of experimental and clinical studies aiming to characterize the biological properties and clinical features of AML and MDS bearing CK and TP53 mutations. Results: These studies have greatly contributed to identifying as separate entities AML and MDS bearing CK and or TP53 alterations. Particularly, the improvement in the methods of detection of chromosome aberrations has contributed to defining the specific nature of the various chromosome abnormalities and to deciphering the mechanisms of catastrophic events leading to gene rearrangements. Two types of CK were identified in AML and MDS, one more frequently associated with TP53 mutations (with poor prognosis) and another less frequently without TP53 mutations (with relatively better prognosis). Conclusions: The treatment of AML and MDS with CK and/or TP53 mutations alterations remains extremely challenging, and the prognosis of these patients is dismal. The main aim of the various induction treatments explored in these patients is to bridge patients to allo-HSCT, the only therapeutic approach able to improve the survival of at least a part of these patients. Full article

Background: Circular RNAs (circRNAs) constitute an emerging research field, as these RNA molecules play a crucial role in cellular functions and the progression of various human pathologies. Little is known about alternative circularization leading to the formation of distinct circRNAs from the same primary transcript, the role of circRNAs with slightly different back-splice junctions (BSJs) resulting in very similar circRNA sequences—called circRNA isoforms—and the extent to which the same primary transcripts produce alternative circRNAs. In this study, we discovered alternative circRNAs produced by two apoptosis-related genes, BAX and BCL2L12, expressed in established human cell lines originating from myelodysplastic syndrome (MDS) and different types of acute myeloid leukemia (AML). Methods: After total RNA extraction from one MDS cell line and five AML cell lines, first-strand cDNA synthesis, and multiple nested PCRs with distinct sets of divergent primers (10 and 16 primer pairs for BAX and BCL2L12 circRNAs, respectively) annealing in each exon of BAX and BCL2L12 genes, amplicon libraries were prepared and sequenced by both nanopore sequencing and NGS. Detailed bioinformatic analysis was then performed, based on existing bioinformatic tools and our own algorithms. Results: Our approach led to the identification of 72 BAX circRNAs and 52 BCL2L12 circRNAs with distinct expression patterns in MDS and AML cell lines. Most of these circRNAs—either merely exonic or exonic–intronic—were detected for the very first time. Furthermore, several BAX circRNA isoforms were detected in a unique cell line. Moreover, the back-splice sites joined together to form the BSJ of each circRNA were non-canonical, in many cases. The identified circRNAs are predicted to sponge distinct sets of miRNAs, some of which are known to regulate the activity of pivotal pathways. Conclusions: Overall, our findings support the notion that alternative splicing and back-splicing lead to the production of tens of distinct circRNAs from the same human gene. Full article

Background/Objectives: Acute myeloid leukemia (AML) with myelodysplasia-related gene mutations (AML-MR), often referred to as secondary AML (s-AML) or AML-MRC, is an aggressive form of leukemia that typically arises from an antecedent myelodysplastic syndrome (MDS) but may also originate de novo. It is characterized by mutations in key genes associated with MDS that include some epigenetic regulators (ASXL1 and EZH2), splicing factors (SF3B1, SRSF2, U2AF1, and ZRSR2), and transcription factors (BCOR, RUNX1, and STAG2). The main objective of this review paper consists of analyzing recent studies that have improved the criteria for the characterization, definition, and classification of AML-MR. Methods: An extensive search of the most recent literature on the topic was performed, selecting and critically analyzing the most relevant studies. Results. The studies carried out in the last few years have provided an extensive molecular characterization of AML-MR, supporting sounder criteria for identification and a better definition with respect to other AML subtypes, particularly with respect to TP53-mutant AML. Conclusions: A unifying classification of AML-MR is now possible, allowing its identification as a unique, well-defined, and separate entity. Full article

Patients with inflammatory bowel disease (IBD) often require long-term immunosuppressive or advanced therapy, raising concerns about treatment-associated malignancy risk. This systematic review evaluated malignancy outcomes associated with biologic, advanced small-molecule, and thiopurine therapies in adults with IBD. PubMed, Embase, the Cochrane Library, and Web of Science were searched from inception through June 2025, with supplementary screening of Google Scholar and reference lists. Eligible primary studies included randomized controlled trials and prospective or retrospective cohort studies evaluating malignancy outcomes. Thiopurines were included because they remain clinically important comparators and are central to combination-therapy risk. The Newcastle–Ottawa Scale and the Cochrane risk-of-bias tool were used for observational studies and randomized trials, respectively. Because of substantial clinical and methodological heterogeneity, we did not perform a de novo meta-analysis; pooled estimates from previously published meta-analyses are reported only as contextual evidence. Twenty-eight studies met the inclusion criteria. Thiopurines showed the most consistent malignancy associations, including lymphoma, non-melanoma skin cancer (NMSC), acute myeloid leukemia/myelodysplastic syndrome, and urinary tract cancer. Anti-tumor necrosis factor (anti-TNF) monotherapy was not associated with a clear increase in overall cancer incidence, although a modest lymphoma signal was reported in some datasets. Combination anti-TNF plus thiopurine therapy showed the strongest lymphoma signal. Current evidence has not demonstrated an increased malignancy risk with vedolizumab or ustekinumab, including in available cohorts of patients with prior malignancy; however, confidence is limited by observational designs, small event numbers, heterogeneous cancer histories, and limited follow-up. IBD-specific data for Janus kinase inhibitors and sphingosine-1-phosphate receptor modulators remain comparatively immature, and long-term surveillance is required. Overall, treatment decisions should integrate absolute baseline risk, age, smoking, prior malignancy, prior NMSC, Epstein–Barr virus-related risk, disease-related cancer risk, and cumulative immunosuppressive exposure. Full article

Aims: Treatment of higher-risk myelodysplastic syndromes (HR-MDS) with azacytidine (AZA) exerts significant effects on the epigenome, primarily through DNA demethylation and reactivation of epigenetically silenced genes. Beyond this established mechanism, molecular AZA-linked effects are increasingly being recognized. Materials and methods: Liquid chromatography combined with mass spectrometry (LC-MS/MS) was employed for the accurate assessment of various RNA and DNA modifications pre- and post-AZA treatment of an HR-MDS cohort (N = 8). Mapping of the AZA treatment-responsive regulatory pathways was performed by miRNA-next generation sequencing (NGS), followed by a multi-layered bioinformatic pipeline, integrating miRNA differential expression, gene set enrichment, and network analyses. The precise number of mitochondrial (mt)DNA copies pre- and post-AZA was evaluated by a digital PCR assay. Results: Cell pathways affected by miRNA differential expression patterns pre- and post-AZA treatment discriminated the clinical phenotypes of Responders against Non-Responders to therapy. Intracellular RNA modifications: N6-methyladenosine (m6A), 5-methylcytidine (m5C), N1-methyladenosine (m1A), 2′-O-methylguanosine (Gm) and adenosine-to-inosine (A → I) editing were evaluated for their potential impact in treatment response. Nuclear DNA/mtDNA methylation profiles and mtDNA copy number reduction manifested the mitochondrial features affected by AZA. Our results suggest that neoplastic HSPCs in HR-MDS Responders to AZA adapt by normalizing glycolytic metabolism and enhancing ribosomal activity. The observed reduction of mtDNA content can be associated with improved survival and suppression of malignant progression. Non-Responders, despite experiencing mtDNA depletion, seem unable to coordinate such metabolic reprogramming and remain disadvantaged to AZA therapy. Full article

Hematological malignancies account for over 1.3 million new cases and approximately 700,000 deaths annually. Despite advances in targeted therapies, immunotherapies, and antibody–drug conjugates, relapse, refractory disease, and acquired drug resistance remain critical challenges. Peptide–drug conjugates (PDCs) have emerged as a promising targeted delivery platform, combining peptide-mediated specificity with potent cytotoxic payloads. In this review, we summarized the fundamental design principles of PDCs, including targeting peptide selection, linker engineering, and payload optimization, with emphasis on the biological characteristics of hematological malignancies. We then examined current preclinical and clinical progress across multiple myeloma, acute myeloid leukemia, myelodysplastic syndromes, B-cell non-Hodgkin lymphoma, and chronic myeloid leukemia. We further discussed emerging strategies such as cathepsin B-responsive PROTAC-PDC hybrids, nanotechnology-assisted delivery, and artificial intelligence-guided molecular design. Finally, we addressed key translational challenges, including tumor heterogeneity, payload resistance, and pharmacokinetic constraints, and proposed future directions toward biomarker-driven precision PDC therapy for hematological malignancies. Full article

Hypomethylating agents (HMAs) are the cornerstone in the treatment of higher-risk myelodysplastic syndromes (MDSs), particularly for patients who are not candidates for allogeneic hematopoietic cell transplant (allo-HCT). Despite demonstrated efficacy in improving hematologic outcomes, the clinical management of HMA-associated myelosuppression remains a challenge. This review discusses the use of azacitidine and oral decitabine-cedazuridine (DEC-C) for MDS management in the Canadian context, with a focus on optimizing therapy to mitigate myelosuppression and prevent early HMA discontinuation due to toxicity. Close monitoring of complete blood counts is critical to early detection of myelosuppression and management of treatment-related cytopenias. In the real-world setting, specific HMA dose adjustments are used based on patient risk factors for myelosuppression or treatment-related complications. Supportive care strategies, including the use of growth factors and antimicrobials, can complement monitoring and dose modifications for HMA-related myelosuppression management, although their use is variable. This review summarizes current evidence and real-world management approaches for HMA-induced myelosuppression, with the aim of improving outcomes for patients undergoing treatment for MDS. Full article

Background/Objectives: Myelodysplastic syndromes (MDS) carry a highly variable prognosis, stratified by the Revised International Prognostic Scoring System (IPSS-R) and the Molecular IPSS (IPSS-M). CEBPA mutations define a favorable-risk subgroup in acute myeloid leukemia (AML), yet their prognostic significance in MDS has not been characterized. Methods: We analyzed 2442 patients from the International Working Group (IWG) 2022 multi-center MDS registry after pre-specified exclusions. Overall survival (OS) and leukemia-free survival (LFS) were compared between CEBPA-mutated (n = 66; 2.7%) and wild-type patients using Kaplan–Meier estimation and Cox proportional hazards regression, adjusting for age, sex, and IPSS-R score; pre-specified subgroup, sensitivity, competing-risk, and mutation subtype analyses were performed. Results:CEBPA-mutated patients had markedly inferior OS (median 17.2 versus 42.2 months; HR 2.05, 95% CI 1.50–2.79; p < 0.001). After IPSS-R adjustment, the hazard ratio remained adverse (HR 1.39, 95% CI 1.00–1.94; p = 0.053), with uniform directionality across all 13 evaluable subgroups and no significant interaction. Co-mutation adjustment for ASXL1 and STAG2 further attenuated the hazard ratio to HR 1.11 (95% CI 0.79–1.57; p = 0.54), suggesting part of the observed signal reflects co-mutation burden rather than an independent CEBPA effect. Competing-risk analysis suggested that the excess mortality is mediated through AML transformation (CEBPA-mutated versus wild-type subdistribution hazard ratio of 1.89, 95% CI 1.20–2.99; p = 0.006) rather than non-transformative MDS mortality (cause-specific HR 0.97; p = 0.890). Truncating mutations drove the adverse signal (HR 2.21; p = 0.023), while basic leucine zipper (bZIP) domain mutations showed no significant effect (HR 1.25; p = 0.470). Conclusions:CEBPA mutations identify a rare MDS subgroup with markedly inferior survival, driven by truncating loss-of-function mutations and associated with leukemic transformation; the AML-derived bZIP-favorable paradigm does not translate to MDS, and CEBPA mutation status merits a prospective study to assess clinical utility for risk stratification. Full article

Background/Objectives: Azacitidine (AZA) is the standard of care for patients with higher-risk Myelodysplastic Syndromes (MDS). There is limited real-life data, however, characterizing its efficacy and safety profile in elderly patients. Methods: We conducted a single-center retrospective cohort chart review to compare front-line AZA therapy in patients ≥75 years (elderly) vs. <75 years (younger) with higher-risk MDS treated at our cancer center. The primary endpoint was overall survival and main secondary endpoints included response, as per the 2006 International Working Group consensus criteria, leukemia-free survival, transfusion independence, and safety outcomes. Results: In total, 55 patients were elderly (median age: 79.9 years), including 27 patients >80 years, and 41 were younger (median age: 69.4 years). Baseline demographic variables were similar between both groups. The majority of elderly patients (98%) received the full dose of AZA (75 mg/m²), compared with 90% of younger patients. The median number of AZA cycles was 8 (range: 2–69) in elderly and 7.75 (range: 1–96) in younger patients. Treatment delays occurred in 36.4% of elderly and 29.3% of younger patients, most commonly due to infection complications in both groups (p = 0.076). Disease control rates (complete remission + partial remission + stable disease) were 92.9% in the younger subgroup and 96.4% in the elderly subgroup (p = 0.154). Relapse occurred in 48.8% of younger patients and 40.0% of elderly patients. Median overall survival (OS) was 17.3 months for the younger subgroup, 15.7 months for the elderly subgroup (p = 0.771), and 11.9 months among patients >80 years (p = 0.381). Mortality rates and causes of death were similar between both subgroups. Most common causes of death included disease progression, sepsis, febrile neutropenia, and pneumonia. Conclusions: AZA monotherapy resulted in a high response rate and was well-tolerated in elderly patients with higher-risk MDS. These findings remain consistent in the real-world setting despite potential confounding factors that may contribute to inferior outcomes. Full article

Background: Chimeric antigen receptor T-cell (CAR-T) therapies have transformed the treatment of haematologic malignancies, yet their adverse event (AE) profiles across all approved agents have not been consolidated using a pharmacovigilance methodology in a single comparative analysis. Methods: Using the FDA Adverse Events Reporting System (FAERS) and OpenVigil 2.1, disproportionality analyses for all six FDA-approved CAR-T therapies were performed, stratified by target antigen: anti-CD19 agents (axicabtagene ciloleucel, tisagenlecleucel, lisocabtagene maraleucel, brexucabtagene autoleucel) and anti-BCMA agents (idecabtagene vicleucel, ciltacabtagene autoleucel). For each of the 25 most frequently reported AEs per agent, the report event counts, reporting odds ratio (ROR) with 95% confidence interval, proportional reporting ratio (PRR), and chi-squared statistic were calculated. Results: A total of 36,567 AEs were identified across all six agents. Cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome were the most frequent and most disproportionate AEs across all six therapies, with RORs exceeding 240 in every agent. Idecabtagene vicleucel had the highest ROR for cytokine release syndrome among all agents (ROR 1934.6), while brexucabtagene autoleucel had the highest ROR for immune effector cell-associated neurotoxicity syndrome (ROR 2089.6). Ciltacabtagene autoleucel exhibited a unique neurological toxicity profile, cranial nerve paralysis (ROR 3167.6, PRR 3055.0, chi² 199,190), parkinsonism (ROR 145.5, PRR 136.6, chi² 24,840), Bell’s palsy (ROR 380.4, PRR 370.3), and facial paralysis (ROR 72.7), consistent with the late neurotoxicity syndrome previously characterized, and absent from other agents’ top 25 AE lists. Brexucabtagene autoleucel demonstrated secondary malignancy signals including squamous cell carcinoma of skin (ROR 308.2) and myelodysplastic syndrome (ROR 97.9). Tisagenlecleucel showed the highest hypogammaglobulinemia signal among all agents (ROR 614.1, PRR 536.5, chi² 144,832) alongside a broad pancytopenia profile. Hemophagocytic lymphohistiocytosis was a significant finding with ciltacabtagene autoleucel (ROR 71.0) and brexucabtagene autoleucel (ROR 57.8). Conclusions: CAR-T therapies share class-wide toxicities in cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, but exhibit clinically important drug-specific and target-class-specific AE profiles. This consolidated FAERS-based analysis corroborates and extends prior pharmacovigilance work by providing direct cross-agent comparisons, and supports the use of agent-tailored monitoring strategies, particularly for the distinctive late neurological toxicity associated with ciltacabtagene autoleucel. Full article

Myelodysplastic syndromes are clonal hematopoietic neoplasms in which ineffective hematopoiesis arises within the context of chronic inflammation and immune dysregulation. Growing evidence indicates that aging-associated inflammaging and inflammation-driven remodeling of the bone marrow microenvironment are not secondary phenomena, but active forces that shape clonal selection, lineage commitment, and disease evolution. This narrative review integrates recent insights from translational immunology, stem cell biology, multi-omics analyses, and clinical studies to examine the reciprocal interplay between inflammation and myelodysplastic syndrome pathogenesis. Chronic inflammatory stress imposes selective pressure on hematopoietic stem cells, favoring the expansion of mutation-bearing clones characteristic of clonal hematopoiesis and overt disease. As inflammation persists, immune dysfunction, together with stromal alterations, progressively reinforce ineffective hematopoiesis and clonal dominance. Genetic lesions, including TP53 and spliceosome mutations, further amplify inflammatory signaling and reshape the marrow niche, conferring clonal fitness and genomic instability. Clinically, readily accessible peripheral blood inflammatory indices reflect these biological processes and correlate with prognosis and therapeutic response. Collectively, these observations position inflammation as a unifying determinant of myelodysplastic syndrome initiation, progression, and treatment sensitivity. Integrating inflammatory signatures with genomic profiling may refine risk stratification and support the development of therapeutic strategies aimed at restoring marrow homeostasis and limiting inflammation-driven clonal evolution. Full article

Relapse remains the leading cause of treatment failure following hematopoietic cell transplantation (HCT) for hematologic malignancies. Circulating tumor DNA (ctDNA) has emerged as a promising minimally invasive biomarker for measurable residual disease (MRD) assessment and early relapse detection; however, the prognostic significance of ctDNA in the post-transplant setting has not been comprehensively synthesized. We conducted a systematic review and meta-analysis in accordance with PRISMA guidelines and registered the protocol in PROSPERO (CRD420261392100). PubMed, Embase, Web of Science, EBSCO, Cochrane CENTRAL, and supplementary sources were searched through November 2025. Eligible studies evaluated tumor-specific ctDNA or tumor-informed/tumor-associated cfDNA in patients undergoing allogeneic or autologous HCT for hematologic malignancies. Random-effects meta-analyses were performed for relapse/progression, overall survival (OS), and relapse-free/progression-free survival (RFS/PFS). Studies evaluating total cfDNA quantity, methylation-based cfDNA profiling, cfRNA, or chimerism-only monitoring were synthesized narratively. Ten observational cohort studies comprising 883 patients met inclusion criteria. Across acute leukemias, lymphomas, multiple myeloma, and myelodysplastic syndromes, ctDNA/cfDNA positivity was consistently associated with adverse outcomes. The pooled hazard ratio (HR) for relapse or disease progression was 12.57 (95% CI: 4.59–34.46; p < 0.001), while pooled HRs were 7.45 (95% CI: 4.11–13.48; p < 0.001) for OS and 4.46 (95% CI: 2.22–8.97; p < 0.001) for RFS/PFS. Although statistical heterogeneity was low, interpretation was limited by the relatively small number of studies contributing to each pooled endpoint. Narrative evidence additionally suggested that broader circulating nucleic acid approaches may provide complementary information regarding graft-versus-host disease, infection, and other post-transplant complications. Tumor-specific ctDNA positivity is consistently associated with increased relapse risk and inferior survival outcomes following HCT. These findings support further investigation of ctDNA-based MRD monitoring as a promising non-invasive biomarker for post-transplant molecular surveillance and risk stratification. However, prospective multicenter validation studies, assay standardization, and ctDNA-guided interventional trials remain necessary before routine clinical implementation can be recommended. Full article

Myeloid malignancies encompass a heterogeneous group of haematological disorders, primarily including myelodysplastic syndromes (MDSs) and myeloproliferative neoplasms (MPNs). MDS is characterised by defective myeloid cell maturation, while MPNs involve the pathological overproduction of myeloid lineage cells. In the absence of timely diagnosis and effective clinical intervention, both entities carry a substantial risk of progression to acute myeloid leukaemia (AML). Although allogeneic haematopoietic stem cell transplantation remains the only potentially curative therapy, its application is frequently constrained by patient-related factors such as advanced age and comorbid conditions. While currently, hypomethylating agent therapy (azacitidine and decitabine) is mainly used in high-risk MDS patients, and ruxolitinib is primarily used in symptomatic primary myelofibrosis (PMF-MPN), their clinical efficacy remains suboptimal. More recently, focus has turned toward the role of the tumour microenvironment (TME) in disease pathogenesis and whether therapeutically targeting the TME, either alone or in combination with conventional therapy, could present a new treatment option. Emerging evidence underscores the significant influence of TME components, particularly macrophages and T cells, in modulating immune responses and shaping the leukaemic niche to either facilitate or hinder malignant progression. In response, a new generation of immune checkpoint inhibitors are being developed to target the TME, including PD-1/CTLA-4 blockers, macrophage-directed agents including CD47 inhibitors, and T cell-targeting checkpoint inhibitors such as TIM-1 and LAG-3. This review will describe the functional role of key TME constituents in the progression of myeloid malignancies and explore the current landscape and future potential of advanced cellular and molecular immunotherapies in the treatment of these disorders. Full article

Background/Objectives: The modified Endothelial Activation and Stress Index (mEASIX), derived from routinely available laboratory parameters, has emerged as a potential biomarker reflecting systemic inflammatory and endothelial stress. However, its prognostic value in myelodysplastic syndromes (MDS) remains incompletely defined. This study evaluated the association between the mEASIX and overall survival and explored its time-dependent prognostic pattern. Methods: This retrospective study included 151 patients with MDS. The mEASIX score was calculated using C-reactive protein, lactate dehydrogenase, and platelet count and was log-transformed for regression analyses. Overall survival was estimated using the Kaplan–Meier method. Univariable and multivariable Cox proportional hazards models were used to evaluate prognostic factors, including age, IPSS-R risk group, hypomethylating agent (HMA) exposure, and venetoclax exposure. The proportional hazards assumption was assessed, and landmark analyses were performed at the median follow-up time (29 months). Receiver operating characteristic analysis was used to determine the optimal mEASIX cut-off value for mortality prediction. Model comparison, internal validation, and sensitivity analyses were also performed. Results: During a median follow-up of 29 months, 85 deaths occurred. The mEASIX yielded an AUC of 0.767 for mortality prediction (95% CI 0.691–0.844; p < 0.001). Patients with a high mEASIX had inferior overall survival (log-rank p < 0.001). In multivariable Cox regression analysis including age, IPSS-R risk group, HMA exposure, and venetoclax exposure, log(mEASIX) remained independently associated with inferior overall survival (HR 1.325, 95% CI 1.166–1.506; p < 0.001). In landmark analyses, this association persisted during the early follow-up period (≤29 months; HR 1.347, 95% CI 1.172–1.548; p < 0.001) but was attenuated during the late period (>29 months; HR 1.287, 95% CI 0.930–1.782; p = 0.128). Conclusions: The baseline mEASIX was independently associated with overall survival in patients with MDS and appeared most prognostically relevant during early follow-up. These findings suggest that the mEASIX may complement established risk models, although further validation is needed before broader clinical use. Full article