This study aimed to evaluate the prognostic significance and clinical impact of the revised 2022 European LeukemiaNet (ELN) classification for acute myeloid leukemia (AML), focusing particularly on patients harboring fms-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutations. A retrospective, multicenter observational study was conducted by the Turkish Society of Hematology-Acute Leukemias Working Group, analyzing 312 adult patients newly diagnosed with AML from January 2012 to December 2022. Patients with acute promyelocytic leukemia were excluded. FLT3-ITD mutations were detected using polymerase chain reaction and, when available, next-generation sequencing. Patients were classified according to the 2017 ELN risk stratification, and FLT3-ITD-positive cases were reclassified based on the updated 2022 ELN criteria. Endpoints were complete remission (CR), disease-free survival (DFS), and overall survival (OS). FLT3-ITD mutations were identified in 54 (17.3%) patients. According to the 2022 ELN classification, 29 patients previously categorized as the favorable (n = 6) or adverse-risk (n = 23) groups were reclassified into the intermediate-risk group, highlighting the substantial impact of removing the FLT3-ITD allelic ratio from risk stratification. With a median follow-up of 31.8 months, OS significantly differed among the 2017 ELN favorable-, intermediate-, and adverse-risk categories (not reached, 21.6 months, and 9.5 months, respectively, p < 0.001). FLT3-ITD-positive patients demonstrated significantly inferior DFS (p = 0.038) and OS (p = 0.009) compared to FLT3-ITD-negative patients. In patients achieving first CR, allogeneic hematopoietic stem cell transplantation (HSCT) improved OS in intermediate-risk (p = 0.003), showed a trend in adverse-risk (p = 0.098), and no benefit in favorable-risk (p = 0.351). Among reclassified FLT3-ITD-positive patients, survival outcomes aligned closely with the original intermediate-risk group defined by the 2017 ELN, supporting the rationale behind the ELN revision. Our findings validate the prognostic utility of the revised 2022 ELN guidelines, especially regarding FLT3-ITD-positive AML, emphasizing that the exclusion of the FLT3-ITD allelic ratio yields a more biologically consistent risk categorization. Furthermore, the data support tailored ELN-based risk stratification for older AML patients. Given the modest benefit of HSCT in adverse-risk patients, future refinements should further stratify this group to address their unmet therapeutic needs and enhance survival outcomes. The study was registered at ClinicalTrials.gov (NCT05979675).

Although systemic inflammation is a well-established prognostic factor in malignancies, composite inflammation-based models remain underexplored in Hodgkin lymphoma (HL). We investigated the prognostic significance of complete blood count (CBC)-derived inflammatory indices and a novel Complete Blood Count Score Model (CBCSM) in patients with H. This study included 80 patients diagnosed with HL. Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and systemic inflammation response index (SIRI) were calculated at diagnosis. Optimal cut-off values for progression-free survival (PFS) and overall survival (OS) were determined using receiver operating characteristic analysis. Survival outcomes were assessed using Kaplan-Meier analysis. Higher NLR, PLR, SII, and SIRI values were significantly associated with shorter PFS and OS (p < 0.01). While clinicopathological factors age, disease stage, and B symptoms predominantly influenced overall survival, CBC-derived inflammatory indices were also associated with both PFS and OS in survival analyses. The composite CBCSM enabled additional risk stratification, with progressively worse outcomes observed across increasing risk categories. Baseline CBC-derived inflammatory indices and the composite CBCSM may provide clinically meaningful prognostic information in HL. Their simplicity, cost-effectiveness, and routine availability make them potentially useful adjuncts to traditional prognostic factors for risk stratification and individualized patient management.

Background: Acute myeloid leukemia (AML) is an aggressive and biologically diverse hematologic cancer that disproportionately affects older individuals. Despite advances in molecular profiling and therapy, long-term outcomes remain unsatisfactory. This nationwide registry was established to provide real-world insights into clinical characteristics, treatment strategies, and survival among adult AML patients in Turkey. Methods: The Turkish AML Registry Project (ClinicalTrials.gov Identifier: NCT05979675) combines retrospective and prospective data from 23 tertiary hematology centers. Adult patients diagnosed between January 2008 and July 2023 were included. Baseline demographics, European LeukemiaNet (ELN) 2017 risk groups, Eastern Cooperative Oncology Group (ECOG) performance status, treatment intensity, and targeted therapy use were analyzed. Response and survival outcomes were assessed using Kaplan–Meier methods. Results: The interim dataset included 891 patients (median age 58 years, 45.5% ≥60). Intensive chemotherapy, most commonly 7 + 3, was applied in 74.1%, while 25.9% received lower-intensity regimens. Targeted agents, mainly venetoclax, were incorporated more frequently into low-intensity therapies (19.1% vs. 3.4%, p < 0.001). Complete remission occurred in 70.2% after intensive and 35.9% after low-intensity therapy, improving to 51.4% with targeted agents. Median overall survival (OS) was 27.2 months, with 1-year OS rates of 54.1%, 28.9%, and 17.6% for favorable, intermediate, and adverse ELN groups (p < 0.001). ECOG 0–1 predicted superior survival (1-year OS 70.3% vs. 47.0%). Conclusions: Nationwide real-world evidence underscores the prognostic relevance of ELN risk and functional status in AML. While intensive chemotherapy remains central, combining targeted agents with low-intensity regimens improves outcomes in less fit patients and supports personalized treatment approaches.

Background: The prognostic significance of extranodal disease in classical Hodgkin lymphoma remains incompletely defined. Although contemporary models such as the Advanced Hodgkin International Prognostic Index (A-HIPI) improve systemic risk stratification, it remains unclear whether outcomes are more closely associated with specific extranodal organ involvement or with the overall burden of extranodal dissemination. Methods: This retrospective single-center study included 89 patients with predominantly advanced-stage classical Hodgkin lymphoma, including a minority of high-risk stage II bulky cases, and documented extranodal involvement at diagnosis. Extranodal disease was evaluated according to both organ-specific involvement and extranodal organ burden (EOB), defined as single extranodal organ involvement (single EO) versus involvement of two or more extranodal organs (≥2 EO). Overall survival (OS) and progression-free survival (PFS) were assessed using Kaplan–Meier analysis and Cox proportional hazard models. Risk stratification was examined using both the International Prognostic Score (IPS) and A-HIPI. Results: Patients with ≥2 EO had significantly inferior OS compared with those with single EO involvement (5-year OS, 66.8% vs. 96.7%; log-rank p = 0.018), whereas the difference in PFS did not reach statistical significance (5-year PFS, 49.6% vs. 73.5%; log-rank p = 0.108). A-HIPI-based stratification significantly discriminated OS (5-year OS, 92.2% vs. 78.2%; p = 0.001) and showed borderline discrimination for PFS (5-year PFS, 71.5% vs. 57.2%; p = 0.053). In the combined analysis, patients with high A-HIPI risk and ≥2 EO had the poorest outcomes, with a 5-year PFS of 34.1% and a 5-year OS of 25.0%. In a parsimonious multivariable Cox model including EOB and A-HIPI-predicted 5-year risk as a continuous variable, ≥2 EO remained associated with inferior OS (HR 3.83, 95% CI 1.34–10.97; p = 0.013), while its association with PFS was adverse but not statistically significant (HR 1.83, 95% CI 0.86–3.88; p = 0.114). Organ-specific extranodal involvement showed limited and inconsistent associations with survival across A-HIPI- and IPS-defined subgroups. Conclusions: In this retrospective single-center cohort, involvement of multiple extranodal organs was associated with inferior OS after adjustment for continuous A-HIPI-predicted risk, whereas its association with PFS did not reach statistical significance. Individual extranodal sites showed no consistent prognostic associations. These exploratory and hypothesis-generating findings suggest that quantitative assessment of extranodal organ burden may complement existing clinical risk measures; however, confirmation in larger, contemporary, externally validated cohorts is required before clinical application.