The European LeukemiaNet (ELN) recommendations have been instrumental in shaping the diagnosis, risk stratification, and management of Philadelphia-negative myeloproliferative neoplasms (MPNs), including polycythemia vera, essential thrombocythemia, and primary myelofibrosis. Over the past two decades, these recommendations have evolved from consensus-based frameworks focused on response standardization to increasingly sophisticated, evidence-based and biologically informed approaches. Early efforts primarily aimed to harmonize response criteria across clinical studies, establishing a foundation for consistent therapeutic evaluation. Subsequent updates introduced risk-adapted treatment strategies centered on thrombotic risk, reflecting the major determinants of morbidity and mortality in these disorders. However, the limitations of surrogate endpoints prompted a shift toward clinically meaningful outcomes, including symptom burden, vascular events, and disease progression. More recent advances have been driven by the integration of molecular genetics and the adoption of structured evidence-based methodologies, enabling refined diagnostic classification and more accurate prognostic assessment. Contemporary ELN frameworks increasingly incorporate dynamic clinical parameters, genomic profiling, and emerging biomarkers, supporting a transition toward individualized, risk-adapted therapeutic strategies. Beyond their role in standardizing MPN management, ELN recommendations have also influenced clinical trial design, endpoint selection, risk stratification, and therapeutic decision-making. Evidence from prospective studies and real-world cohorts supports the clinical applicability of these frameworks, although their implementation remains heterogeneous across healthcare settings. This review provides a comprehensive and critical overview of the evolution and implementation of ELN recommendations, highlighting their impact on clinical research and routine practice, current limitations, and future directions toward precision medicine in Philadelphia-negative MPNs.
R-GDP has been established as an effective salvage treatment for Rel/Ref DLBCL. We aimed to clarify the efficacy of R-GDP therapy. We included 41 consecutive patients with Rel/Ref DLBCL, who received R-GDP therapy as salvage chemotherapy at our hospital between January 2014 and August 2024. Thirty-three patients received R-GDP therapy as a 2nd-line regimen, whereas 8 received R-GDP as a 3rd or later-line regimen. The ORR was 70.7%. 23 out of 25 relapsed patients (92%) responded to R-GDP therapy, whereas only 6 out of 16 refractory patients responded (37.5%). With regard to the duration of response, the response rates in 19 patients with late relapse (at least 12 months) and 6 with early relapse (less than 12 months) were 94.7% and 83.3% (p = 0.43). Overall, the 2-year PFS and OS rates were 48.8% and 74.2%, respectively. 18 responders underwent ASCT with a 2-year PFS after ASCT of 61.2%. Although CAR-T is recommended in patients with Rel/Ref DLBCL, R-GDP is a realistic option given the limited availability of immediate CAR-T therapy. Further studies including genomic profiles are warranted to identify factors that can predict a response to R-GDP in Rel/Ref DLBCL.
5-azacitidine (5-AZA) is the first hypomethylating agent synthetized and the cornerstone treatment for high-risk myelodysplastic neoplasms (MDS) and chronic myelomonocytic leukaemia (CMML). Although the validated schedule is 75 mg/m2 for 7 days (7-0-0), alternative schedules have been studied in terms of efficacy, complications and survival. The 7-0-0 shows an overall survival (OS) between 21 and 25 months in prospective and 16.5-27 months in retrospective studies and complete response (CR) rates between 7% and 18%. Alternative schedules, mostly 5-day (5-0-0) or 7-day with weekend pause (5-2-2) at 75 mg/m2, perform equally in terms of OS and CR with the 7-0-0, with a slight superiority for the 5-2-2, although direct comparisons are rare and almost always non-significant. Similarly, transfusion independence, time to leukaemia transformation and toxicities did not differ significantly across studies. For more intensive schedules, using 100 mg/m2 for 5 days, literature is limited, but response rates, survival and safety seem to be comparable to the 75 mg/m2 dose. In CMML, 5-AZA monotherapy yields satisfying overall response rates of 40% or more, with myelodysplastic subtype responding better than myeloproliferative. In all, alternative 5-AZA schedules seem non-inferior in terms of efficacy and toxicities and can be used as an alternative according to local protocols and patient choice.
Treatment options after venetoclax-hypomethylating agent (Ven-HMA) failure in acute myeloid leukemia (AML) remain limited, with a median overall survival of 2-3 months. Cladribine targets biologically distinct leukemia stem cells, including monocytic populations implicated in venetoclax resistance. We conducted a multicenter retrospective study across six Israeli academic centers to evaluate cladribine-based salvage therapy, predominantly cladribine, low-dose cytarabine, and venetoclax (CAV), in 31 patients with relapsed/refractory AML. Median age was 70 years (range 21-81); 87% had prior venetoclax exposure, 61% had undergone prior allogeneic transplantation, and 55% were classified as ELN-2022 adverse risk. After a single treatment course, the composite complete remission rate (CRc) was 45% and the overall response rate was 52%. Median overall survival was 5 months, with a 1-year survival of 30%. Patients achieving CRc had significantly longer survival (16.2 vs. 2.9 months; p < 0.0001). Twelve patients (39%) were bridged to cellular therapy, with a median survival of 12.6 months. Toxicity was predominantly hematological; invasive fungal infection occurred in 23% and was associated with fluconazole rather than mold active prophylaxis. The 30-day mortality was 19%. Cladribine-based salvage demonstrates clinically meaningful activity after Ven-HMA failure and can bridge patients to cellular therapy.
BACKGROUND:Acute myeloid leukemia (AML) often coincides with type 2 diabetes mellitus (T2D), yet the impact of metabolic comorbidity on leukaemic biology and prognosis remains underexplored. METHODS:We integrated two transcriptome-derived stemness indices (mRNAsi, EREG.mRNAsi) with weighted gene-co-expression network analysis (WGCNA) in 137 TCGA-LAML samples. Higher stemness scores clustered with adverse cytogenetics, and a stemness-linked "brown" module yielded 13 candidate genes. We prospectively enrolled 152 newly diagnosed AML patients with confirmed T2D. Peripheral-blood RNA quantification placed patients into INTS7-high and INTS7-low groups by cohort median. RESULTS:INTS7 not only predicted overall survival in TCGA but also retained significance in four independent GEO cohorts (total n = 306). Importantly, GWASdb ranks INTS7 as a significant T2D locus (standardised score ≈ 0.57), suggesting shared pathogenic circuits between dysglycaemia and leukaemia. Baseline demographics, BMI, counts and ELN-2022 risk were balanced, yet complete-remission after induction therapy was 41% versus 96% (p < 0.001). Kaplan-Meier analysis showed that high INTS7 expression halved median overall (18.2 vs 41.3 months) and progression-free survival (10.1 vs 24.8 months); multivariable Cox models confirmed independent adverse impact (HR_OS = 2.05; HR_PFS = 2.33). The effect size exceeded that in unselected AML, indicating that diabetic physiology amplifies INTS7-driven chemoresistance. CONCLUSION:Our integrative approach-linking stemness metrics, network modelling and comorbidity-focused validation-identifies INTS7 as a biomarker at the nexus of metabolic disorder and leukaemic aggressiveness. Quantifying INTS7 could refine risk stratification and inspire metabolism-tailored therapeutic strategies for the growing AML-T2D population.
BACKGROUND:Ferroptosis, a form of regulated cell death driven by iron-dependent lipid peroxidation, has emerged as a potential therapeutic target in various cancers, including diffuse large B-cell lymphoma (DLBCL). This study aimed to identify and characterize ferroptosis-related panel genes with prognostic value in DLBCL. METHODS:Transcriptomic data from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) were analyzed to identify differentially expressed genes (DEGs) in DLBCL samples. Gene set variation analysis (GSVA) and network topology analysis were performed to identify key ferroptosis-related genes. Lasso regression was utilized to construct a prognostic model based on the identified panel genes. In vitro experiments, including gene silencing, overexpression, and ferroptosis induction, were conducted to evaluate the functional roles of the identified genes, NUMA1 and SLC1A5, in DLBCL cells. RESULTS:A panel of ferroptosis-related genes with prognostic value, including NUMA1 and SLC1A5, was identified in DLBCL samples. Silencing SLC1A5 or overexpressing NUMA1 in DLBCL cells enhanced sensitivity to ferroptosis inducers, increased intracellular labile iron and lipid peroxidation levels, promoted mitochondrial damage, and modulated the expression of key ferroptosis markers. Furthermore, SLC1A5 silencing or NUMA1 overexpression augmented radiation-induced ferroptosis in DLBCL cells. CONCLUSION:NUMA1 and SLC1A5 are potential ferroptosis regulators and therapeutic targets in DLBCL. Silencing the ferroptosis-suppressive transporter SLC1A5 or restoring NUMA1 expression promotes lipid peroxidation and ferroptotic cell death, thereby sensitizing DLBCL cells to ferroptosis and enhancing radiosensitivity-providing a rationale for novel ferroptosis-based therapeutic strategies.
PURPOSE:Newly diagnosed pediatric B-cell acute lymphoblastic leukemia (B-ALL) patients who require modification of standard chemotherapy because of severe treatment-related toxicities or inadequate early response represent an understudied population with limited therapeutic evidence. We evaluated the efficacy and safety of blinatumomab in this real-world clinical setting. METHODS:We conducted a retrospective, single-center analysis of 15 pediatric patients with newly diagnosed CD19-positive B-ALL treated with blinatumomab between May 2022 and December 2024 because of severe chemotherapy-related toxicities, inadequate early response, or individualized treatment modification. Clinical response, minimal residual disease (MRD) status, hematologic parameters, and adverse events (AEs) were evaluated before and after therapy. RESULTS:Most patients (86.7%) presented with high tumor burden at diagnosis. Notably, eleven patients received a 14-day course, two patients received a 16-day course, and two patients completed the standard 28-day treatment cycle. Following one cycle, blinatumomab induced MRD-negative remission in all six patients with persistent disease before treatment (four with MRD positivity and two with >5% residual bone marrow blasts). The remaining nine patients had already achieved MRD-negative remission after chemotherapy but received blinatumomab because further chemotherapy could not be continued owing to severe treatment-related toxicities; all maintained MRD-negative status during subsequent blinatumomab therapy. Significant improvements were observed in white blood cell counts, hemoglobin, and platelet levels compared with baseline (all P < 0.05). The most frequent AEs were fever (66.7%), neutropenia (40.0%), elevated transaminases (26.7%), and neurological symptoms (20.0%). All AEs were manageable and reversible; no treatment-related deaths occurred. CONCLUSIONS:Blinatumomab demonstrated encouraging efficacy and a favorable safety profile in newly diagnosed pediatric B-ALL patients requiring modification of standard chemotherapy. It achieved MRD clearance in patients with residual disease while maintaining MRD-negative remission in those unable to continue conventional chemotherapy because of severe toxicities, and was associated with rapid hematologic recovery. An abbreviated 14-day regimen also appeared feasible and well tolerated in this real-world cohort.
The chromosomal translocation t(4;11)(q21;q23) is the most common genetic aberration in KMT2A-rearranged acute leukemia. Although the molecular functions of wild-type KMT2A and AFF1 complexes are well characterized, little is known about the interplay between the reciprocal fusion proteins KMT2A::AFF1 (MA4) and AFF1::KMT2A (A4M). Here, we established model systems to investigate this interplay and the role of the RNA-binding proteins IGF2BP1-3. We also compared the murinized fusion KMT2A::mAff1 (MmA4) with the authentic human KMT2A::AFF1 fusion. Our data indicate that MA4 alone drives aberrantly high expression of only a few target genes, whereas A4M counteracts this detrimental effect. Under these conditions, MA4 induces genes encoding RNA-binding proteins as a counterregulatory response. Both reciprocal fusion transcripts are bound by IGF2BP3, resulting in reduced MA4 protein abundance but increased A4M levels. This effect was not observed for the artificial MmA4 fusion, likely because it cannot recruit the SL-1 complex. Together with previous findings, our results suggest that A4M is crucial through its chromatin-opening activity, which strongly expands the pool of MA4 target genes and thereby promotes the establishment of pre-leukemogenic and leukemogenic gene expression programs.
BACKGROUND:Several studies conducted in high-income countries (HICs) have demonstrated that treatment intensification in pediatric T-cell acute lymphoblastic leukemia (T-ALL) improved survival outcomes. However, studies in low- and middle-income countries (LMICs) remain scarce. In this study, we evaluated survival rates and their associations with clinical factors within the context of the Brazilian Unified Health System. METHODS:Data from 86 patients aged 0-19 years, diagnosed with T-ALL at one of four pediatric oncology reference centers of the Brazilian Unified Health System, were included in the study. Clinical, demographic, and laboratory variables were collected through a retrospective analysis of medical records. RESULTS:Cohort survival rates revealed that the 5-year overall survival probability (pOS) and event-free survival probability (pEFS) for patients with T-ALL were 47% (37.3-59.3) and 43.2% (33.5-55.7), respectively, with infection being the main cause of death (69.4%). In both bivariate and multivariate analyses, the presence of adenomegaly at diagnosis was associated with lower pOS and pEFS. In addition, the GBTLI-HR protocol achieved the highest pOS (70.0%), compared to the 35.0% and 32.0% observed with the ALL IC-BFM 2002-HR and ALL IC-BFM 2009-HR protocols, respectively. This reinforces the need for context-specific adaptations of intensive treatment protocols in LMICs. CONCLUSION:This study offers valuable insights into the clinical and demographic characteristics of patients with T-ALL from Brazil, highlighting substantially higher mortality rates than those reported in HICs, primarily attributed to high infection rates.
Arterial stiffness, measured by pulse wave velocity (PWV), is a validated surrogate of vascular damage and CV risk, but evidence on TKI-specific patterns of arterial stiffness and their prognostic relevance in chronic myeloid leukemia (CML) is limited. We primarily evaluated the longitudinal association between TKI type and arterial stiffness, and secondarily explored the association between arterial stiffness and CV adverse events (CVAEs). In this prospective cohort study, 69 patients with CML receiving imatinib (n = 30), dasatinib (n = 18), or nilotinib (n = 21) underwent non-invasive assessment of carotid-femoral PWV. Longitudinal PWV trajectories were analyzed with prespecified adjustment sets including key clinical and hematologic-inflammatory covariates. Associations between PWV and CVAEs were explored. No significant interaction between time and TKI type was observed in unadjusted (χ²=1.81, p = 0.41), clinically adjusted (χ²=1.60, p = 0.45), or hematologic-inflammatory adjusted LME models (χ²=1.68, p = 0.43). During a median follow-up of 19 months, 21 CVAEs occurred. Higher PWV was associated with CVAEs after multivariable adjustment (OR = 1.40, p = 0.037), together with ≥ 2 TKI treatment lines (OR = 2.70, p = 0.042). In this real-world cohort, no evidence of differential longitudinal progression of arterial stiffness according to TKI type was detected. Arterial stiffness and treatment-related variables were associated with CVAEs, whereas no differential PWV trajectory according to TKI type was detected. These findings are exploratory and require validation in larger prospective cohorts with longer follow-up before definitive clinical recommendations can be made.
BACKGROUND:Myeloid sarcoma is a rare extramedullary tumor of immature myeloid cells, most commonly associated with acute leukemia, but also seen in chronic myeloid neoplasms or as an isolated lesion (de novo). These different clinical contexts suggest biological heterogeneity with potential prognostic implications. This study aimed to analyze clinicopathological features and survival outcomes across these three subgroups in a large single-center cohort. METHODS:This retrospective study included 126 histologically confirmed cases of myeloid sarcoma diagnosed at UPUMS Saifai between January 2024 and April 2026. Cases were stratified into acute leukemia-associated (EMMT-AL), chronic myeloid neoplasm-associated (EMMT-CMN), and de novo groups. Clinicopathological features, immunohistochemical profiles, and survival outcomes were analyzed using Kaplan-Meier and Cox regression analyses. RESULTS:Among 126 cases, 68 (54.0%) were EMMT-AL, 36 (28.6%) were EMMT-CMN, and 22 (17.5%) were de novo. The cohort comprised 84 males (66.7%) and 42 females (33.3%). Median age was 35 years (range: 1-78). Site distribution varied significantly: nodal involvement predominated in EMMT-CMN (58.3%), while head and neck region was most common in EMMT-AL (29.4%) and de novo (22.7%) groups. The blastic variant was the most frequent histologic subtype (54.8%). The 2-year overall survival for the entire cohort was 38.5%, with significant differences between groups: 22.1% (EMMT-AL), 67.8% (EMMT-CMN), and 51.2% (de novo) (log-rank p < 0.0001). In EMMT-AL, CD34 expression by immunohistochemistry was associated with inferior overall survival (p = 0.024). In EMMT-CMN, absence of excess marrow blasts (p = 0.015) and differentiated histologic morphology (p = 0.041) predicted better outcomes. CONCLUSION:Myeloid sarcoma exhibits distinct clinicopathological and prognostic differences based on underlying hematologic disease. Stratification into acute leukemia-associated, chronic myeloid neoplasm-associated, and de novo categories identifies clinically relevant subgroups with significantly different outcomes.
OBJECTIVE:To analyze the efficacy and safety of ifosfamide + vincristine + dexamethasone/etoposide + mitoxantrone (IVD/EM) regimen as maintenance therapy in adult patients with T-cell lymphoblastic lymphoma/leukemia (T-LBL/ALL). A total of 53 patients with T-LBL/ALL were enrolled, with a median age of 27 (range, 18-73) years and a male-to-female ratio of 2.5:1. Compared with the transplantation group, the 1‑, 3‑, and 5‑year progression‑free survival (PFS) rates in the alternating maintenance group were 77.8% vs 71.4%, 66.7% vs 64.8% and 58.3% vs 60.7%, respectively; the 1‑, 3‑, and 5‑year overall survival (OS) rates were 94.4% vs 74.3%, 66.2% vs 71.4% and 66.2% vs 71.4%, respectively. No statistically significant differences were observed in PFS and OS rates between the two groups (P = 0.908; P = 0.972). Although the recurrence rate in the maintenance group tended to be higher than that in the transplantation group (P = 0.129), non‑relapse mortality was significantly reduced in the alternating maintenance group (P = 0.046). Multivariate analysis demonstrated that male and elevated β2‑microglobulin levels were independent adverse factors for PFS in patients with T‑LBL/ALL (P < 0.05), while the presence of elevated β2-microglobulin levels at diagnosis was an independent prognostic factor for OS (P < 0.05). SAFETY:In terms of safety, adverse events in the alternating maintenance group were predominantly grade 1-2, and no treatment-related deaths were observed. CONCLUSION:The IVD/EM maintenance regimen is safe and effective in post-remission therapy for adult patients with T-LBL/ALL.
BACKGROUND:Acute myeloid leukemia (AML) predominantly affects older adults; however, patients aged ≥ 80 years remain underrepresented in clinical trials, and their real-world outcomes and prognostic determinants remain unclear. METHODS:This multicenter retrospective cohort study (SNOWFALL: Study of Northern Outcomes With Frailty and Acute Leukemia in Late Life) used the Hokkaido Leukemia Net registry. Consecutive patients aged ≥ 80 years with newly diagnosed AML between 2020 and 2024 were analyzed. Clinical characteristics, treatments, overall survival (OS), relapse-free survival (RFS), cumulative incidence of relapse (CIR), and prognostic performance of a clinical-biological risk score were evaluated. RESULTS:A total of 154 patients (median age, 84 years) were evaluated, with a median OS of 237 days. Although unadjusted OS did not differ significantly between patients aged 80-84 years and those aged ≥ 85 years, multivariable analysis identified age ≥ 85 years, Eastern Cooperative Oncology Group performance status (ECOG PS) ≥ 2, and high clinical-biological risk as independent adverse factors for OS. Increasing age and ECOG PS ≥ 2 were independently associated with 30-day mortality (odds ratios per year, 1.16 and 3.35, respectively). RFS and CIR did not differ significantly by age group. Non-relapse mortality analysis showed no significant trend toward higher NRM in patients aged ≥ 85 years and those with ECOG PS ≥ 2. CONCLUSIONS:In this real-world cohort, patients aged ≥ 80 years demonstrated poor outcomes. Prognosis may be more strongly associated with clinical vulnerability than with chronological age or relapse-related outcomes, highlighting the limitations of age-based risk models and the need for refined, clinically informed risk stratification and treatment strategies tailored to very elderly patients with AML.
BACKGROUND:The Signaling Lymphocyte Activation Molecule (SLAM) receptor family regulates immune homeostasis across diverse immune cells. This study investigates the immunomodulatory role of CD244 in CD8+T cells within the acute myeloid leukemia (AML) bone marrow microenvironment. METHODS:Using pan-cancer analysis, Gene Expression Omnibus (GEO) datasets, functional experiments, and orthotopic AML mouse models, we systematically evaluated CD244 expression and its correlations with gene mutations, clinical prognosis, and immune microenvironment profiles in AML. RESULTS:Pan-cancer analysis revealed high CD244 expression in AML, associated with poor prognosis. GSE6891 data showed biallelic CEBPA mutations upregulated CD244, while NPM1 mutations had lower expression. TCGA-LAML analysis linked CD244 to immune cell infiltration. Flow cytometry validated elevated CD244 on bone marrow-infiltrating CD8+T cells, predominantly on terminally differentiated effector memory T subsets in AML patients, with impaired cytokine secretion compared to healthy controls. Orthotopic AML mouse models also confirmed enhanced CD244 expression in CD62Llow/highCD44high CD8+T cell subsets. Additionally, CD244 correlated positively with CD161/CD57 and negatively with CD27. And anti-CD244 antibody could significantly enhance T-cell-mediated anti-AML efficacy in cytotoxicity assays. CONCLUSIONS:CD244 drives immunomodulation via dysregulated CD8+T cell differentiation and cytokine secretion, positioning it as a prognostic biomarker and a promising target for immunotherapy in AML.
Management of relapsed or refractory acute leukemia remains challenging, as allogeneic transplantation is the only curative option. Although targeted therapies are increasingly incorporated as bridge-to-transplant strategies in both AML and ALL, conventional chemotherapy regimens such as FLAMSA and FLAG-IDA remain important salvage options for patients without targetable molecular alterations or when access to targeted therapies is limited. There are no head-to-head comparative data for these two regimens. We retrospectively evaluated 102 adults with relapsed or refractory AML or ALL who were treated with FLAMSA or FLAG-IDA as salvage regimens between 2010 and 2023, including primary refractory patients and those relapsing after Allo-HCT. Among patients treated with the intent to transplant (n = 86), CR/CRi rates after one cycle were comparable (66.1%vs.58.3%; p = 0.38). FLAMSA was associated with shorter durations of neutropenia (25.5 vs.29 days; p = 0.031), thrombocytopenia (23.5 vs.30.5 days; p < 0.001), and hospitalization (24.5 vs.31 days; p = 0.02), as well as a lower incidence of bacterial pneumonia (16.7%vs.38.7%; p = 0.04) and septic shock or ICU admission (12.5%vs.35.5%; p = 0.03). In the AML subgroup, post-transplant survival was numerically higher in patients treated with FLAG-IDA (2-year OS: 66.4% vs. 36.2%, p = 0.11; 2-year RFS: 63.4% vs. 33.7%, p = 0.07), although differences did not reach statistical significance. In the ALL subgroup, survival outcomes were comparable between the two regimens (2-year OS: 47.0% vs. 33.3%, p = 0.83; 2-year RFS: 35.0% vs. 33.3%, p = 0.98). In multivariate analysis, the choice of salvage regimen (FLAMSA vs FLAG-IDA) was not associated with overall survival (HR 1.05, 95% CI 0.43-2.57; p = 0.899), whereas high-risk disease independently predicted inferior survival (HR 3.24, 95% CI 1.36-7.75; p = 0.008). Among patients relapsing after Allo-HCT (n = 16), CR/CRi rates and the proportion proceeding to second transplantation did not differ. In this single-center cohort, FLAMSA was associated with a more favorable toxicity profile than FLAG-IDA, while overall outcomes were broadly comparable between the two regimens. Given the potential impact of historical confounding, these findings warrant validation in additional cohorts.
BACKGROUND:Isocitrate dehydrogenase inhibitors (IDHi) for IDH-mutated acute myeloid leukemia (AML) are important treatment options for older adults in whom treatment-related toxicities are a major concern. Long-term data on IDHi are limited. METHODS:We conducted a single-center retrospective study of patients aged ≥ 65 years with newly diagnosed or relapsed/refractory IDH-mutated AML who received ivosidenib or enasidenib for ≥ 2 continuous years and either achieved complete remission (CR) or initiated therapy in CR as maintenance. RESULTS:Nine patients were identified with median treatment duration of 6.88 years (range: 1.94-8.87). Median age at IDHi initiation was 71 years (range: 65-84); 44% were ≥ 75 years. Six patients (67%) had IDH1 mutations and 3 (33%) had IDH2 mutations. Median number of mutated genes per patient was 4 (range: 1-6). There were no mutations in the receptor tyrosine kinase pathway. Four patients began IDHi at diagnosis, 3 upon relapse, and 2 as maintenance following first CR. No differentiation syndrome occurred. Seven patients (78%) remain on IDHi and in CR; both who relapsed had antecedent myeloid neoplasms. At median follow-up of 6.88 years (range: 2.62-8.87), median event-free survival (EFS) and overall survival (OS) were not reached. Five-year EFS and OS were 78% (95% CI: 55-100) and 88% (95% CI: 67-100), respectively. CONCLUSIONS:This selected real-world cohort demonstrates durable responses exceeding published benchmarks and has one of the longest follow-up periods reported for IDHi in AML. A subset of older adults with IDH-mutated AML can achieve highly durable remissions on IDHi without significant toxicity.
