Hemato

Background/Objectives: Tyrosine kinase inhibitors (TKIs) have transformed the treatment of chronic myeloid leukemia (CML), yet emerging evidence indicates an increased risk of vascular adverse events, particularly peripheral artery disease (PAD). Reliable biomarkers for early detection of TKI-related vascular toxicity are still lacking. Methods: A cross-sectional study was conducted on 78 patients with chronic-phase CML treated at Dr. Soetomo General Hospital, Surabaya. PAD was confirmed using ankle–brachial index. Serum oxidized low-density lipoprotein (OxLDL) and interleukin-10 (IL-10) levels were measured using ELISA. Results: PAD was detected in 20% of subjects. The PAD group showed significantly higher OxLDL, lower IL-10, and a markedly elevated OxLDL/IL-10 ratio (all p < 0.001). OxLDL remained independently associated with PAD after adjustment (adjusted OR = 1.132, 95% CI 1.020–1.255, p = 0.019). OxLDL/IL-10 ratio yielded a good diagnostic value (sensitivity 87.5% and specificity of 88.7%). Conclusions: Elevated OxLDL and an increased OxLDL/IL-10 ratio are associated with PAD in CML patients receiving TKI therapy and demonstrated a good diagnostic performance for early detection of TKI-induced vascular toxicity.

Introduction: Ropeginterferon alfa-2b is an emerging treatment for polycythemia vera, with growing interest in its application for essential thrombocythemia and early myelofibrosis due to its extended dosing intervals and favorable tolerability profile. However, real-world evidence regarding its dosing strategies and titration practices remains limited. Objective: This study examined seven younger patients, all under 60 years of age, who were treated with ropeginterferon alfa-2b. Materials and Methods: This study is a retrospective medical records review of consecutive patients from seven hospitals. Treatment was initiated at a dose of 250 micrograms, with a maintenance dose of 500 micrograms. Results: The regimen demonstrated good safety and tolerability in this real-world setting. Hematological responses were observed, along with a meaningful reduction in JAK2V617F variant allele frequency across the patient cohort. Conclusions: These findings show that the use of high-initial-dose accelerated titration (HIDAT) regimen of ropeginterferon alfa-2b is a safe and effective treatment option for younger patients with myeloproliferative neoplasms.

Background: The emergence of therapy-related myelodysplastic syndrome (t-MN) after autologous stem cell transplantation (ASCT) is well documented. However, with the growing use of chimeric antigen receptor (CAR) T-cell therapy for relapsed/refractory B-cell malignancies, concerns about secondary myeloid neoplasms, particularly MN, have arisen. The mechanisms and cytogenetic features associated with post-CAR-T MN, especially chromosome 7 abnormalities, remain underexplored. Objectives: To compare the incidence, timing, and cytogenetic characteristics of MN developing after CAR-T-cell therapy versus ASCT, and to evaluate the potential association between CAR-T therapy, persistent cytopenias, and these specific alterations. Study Design: This was a retrospective, single-center study of 275 patients with B-cell malignancies treated between 2015 and 2024 at Hospital Universitario Central de Asturias (Spain). Of these, 259 patients underwent ASCT and 16 received CAR-T-cell therapy (axicabtageneciloleucel n = 13, tisagenlecleucel n = 2, brexucabtageneautoleucel n = 1). Clinical, cytogenetic, and laboratory data were collected and analyzed. Incidence rates were compared using Fisher’s exact test, and time-to-event outcomes was evaluated using the Mann–Whitney U test (given the small number of events). Statistical significance was set at p < 0.05. Results: Myeloid neoplasms were diagnosed in 3 of 259 ASCT patients (1.15%) and in 2 of 16 CAR-T-cell patients (12.5%) (p = 0.03). The median time to myeloid neoplasm diagnosis was numerically shorter in the CAR-T group (15.5 vs. 69 months, p = 0.096). All post-CAR-T cases presented persistent cytopenias and cytokine release syndrome (CRS). Cytogenetic analyses revealed de novo monosomy 7 and 7q deletion in both CAR-T-related cases, whereas no chromosome 7 abnormalities were detected in ASCT-related cases. Pre-treatment samples did not show these abnormalities, although limitations in the sensitivity of the assays preclude the definitive exclusion of minor pre-existing clones. Both affected CAR-T patients had prolonged CAR-T cell persistence and required transfusional support due to hematologic toxicity. One patient was diagnosed with high-risk MN with 5q and 7q deletion and the other with Clonal Cytopenia of Uncertain Significance (CCUS) with monosomy 7. Conclusions: CAR-T-cell therapy was associated with a significantly higher and earlier incidence of myeloid neoplasms compared to ASCT in this cohort. The development of post-CAR-T myeloid neoplasm was characterized by persistent cytopenias, prolonged CAR-T cell persistence, and de novo chromosome 7 alterations. While the small sample size necessitates cautious interpretation, these findings may suggest a distinct pathogenesis potentially linked to inflammation, immune toxicity, or the expansion of pre-existing clones. This highlights the need for long-term hematologic monitoring and evaluation for clonal hematopoiesis prior to CAR-T-cell therapy, especially in heavily pretreated patients.