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Background: There are no studies assessing the evolution and patterns of genetic studies performed at diagnosis in acute myeloid leukemia (AML) patients. Such studies could help to identify potential gaps in our present diagnostic practices, especially in the context of increasingly complex procedures and classifications. Methods: The REALMOL study (NCT05541224) evaluated the evolution, patterns, and clinical impact of performing main genetic and molecular studies performed at diagnosis in 7285 adult AML patients included in the PETHEMA AML registry (NCT02607059) between 2000 and 2021. Results: Screening rates increased for all tests across different time periods (2000–2007, 2008–2016, and 2017–2021) and was the most influential factor for NPM1, FLT3‐ITD, and next‐generation sequencing (NGS) determinations: NPM1 testing increased from 28.9% to 72.8% and 95.2% (p <.001), whereas FLT3‐ITD testing increased from 38.1% to 74.1% and 95.9% (p <.0001). NGS testing was not performed between 2000–2007 and only reached 3.5% in 2008–2016, but significantly increased to 72% in 2017–2021 (p <.001). Treatment decision was the most influential factor to perform karyotype (odds ratio [OR], 6.057; 95% confidence interval [CI], 4.702–7.802), and fluorescence in situ hybridation (OR, 2.273; 95% CI, 1.901–2.719) studies. Patients ≥70 years old or with an Eastern Cooperative Oncology Group ≥2 were less likely to undergo these diagnostic procedures. Performing genetic studies were associated with a favorable impact on overall survival, especially in patients who received intensive chemotherapy. Conclusions: This unique study provides relevant information about the evolving landscape of genetic and molecular diagnosis for adult AML patients in real‐world setting, highlighting the increased complexity of genetic diagnosis over the past 2 decades. A retrospective analysis of 7285 cases over 2 decades. This study explores the evolution of diagnostic practices in acute myeloid leukemia patients, highlighting factors influencing test implementation and their association with patient outcomes. [ABSTRACT FROM AUTHOR]

Background: It is widely accepted that allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only potentially curative option available for secondary Acute Myeloid Leukemia (sAML). However, clinical factors impacting outcomes after allo-HSCT and the potential role of autologous-HSCT (auto-HSCT) in real-life series are needed. Previously, the PETHEMA group reported a series of 2310 patients with sAML within the nationwide registry. Out of them, 876 were candidates to receive chemotherapy and 274 patients (55 auto-HSCT and 219 allo-HSCT)., Objective: In this work, we have analyzed the role auto-HSCT (N=55) or allo-HSCT (N=219) as front-line treatment for sAML patients included in AML Spanish PETHEMA registry. In this paper, we analyze outcomes as well as prognostic variables in this series of patients undergoing auto- or allo-HSCT as part of the front-line treatment for sAML., Study Design: We used the multinational PETHEMA AML registry (NCT02607059) to identify adult patients (age ≥18 years) with a diagnosis of sAML who received auto- or allo-HSCT as front-line treatment in Spanish and Portuguese institutions from August, 1 st 1992 until July, 31 st 2020). Patient characteristics, diagnostic findings, and management, including treatments, characteristics of HSCT and outcomes, were retrieved from the PETHEMA AML registry in this retrospective multicenter analysis., Results: With a median follow-up of 32.7 months, better 5-year OS and LFS were obtained with allo-HSCT in CR1 (44.5% and 39.9%, respectively), as compared with auto-HSCT in CR1 (30% and 20.5%, respectively) but without reaching statistical differences for OS (p= 0.22 and p=0.03). The higher incidence of relapse in auto-HSCT is counterbalanced with the significantly low NRM rate. For allo-HSCT patients, 5-year outcomes were significantly influenced by the cytogenetic/genetic risk. In multivariate analysis, adverse cytogenetic/genetic risk group retained statistical significance for all endpoints., Conclusion: As conclusions, we confirmed the role of allo-HSCT as a potential curative option for patients and we report that auto-HSCT in CR can still provide a 5-year LFS of 20% in sAML patients. Finally, our results confirm adverse cytogenetic/genetic risk category as an independent negative factor in sAML patients receiving HSCT., (Copyright © 2025. Published by Elsevier Inc.)

Treatment options for patients with secondary acute myeloid leukemia (sAML) and AML with myeloid-related changes (AMLMRC) aged 60 to 75 years are scarce and unsuitable. A pivotal trial showed that CPX-351 improved complete remission with/without incomplete recovery (CR/CRi) and overall survival (OS) as compared with standard "3+7" regimens. We retrospectively analyze outcomes of 765 patients with sAML and AML-MRC aged 60 to 75 years treated with intensive chemotherapy, reported to the PETHEMA registry before CPX-351 became available. The CR/CRi rate was 48%, median OS was 7.6 months (95% confidence interval [CI]: 6.7-8.5) and event-free survival (EFS) 2.7 months (95% CI: 2-3.3), without differences between intensive chemotherapy regimens and AML type. Multivariate analyses identified age ≥70 years, Eastern Cooperative Oncology Group performance status ≥1 as independent adverse prognostic factors for CR/CRi and OS, while favorable/intermediate cytogenetic risk and NPM1 were favorable prognostic factors. Patients receiving allogeneic stem cell transplant (HSCT), autologous HSCT, and those who completed more consolidation cycles showed improved OS. This large study suggests that classical intensive chemotherapy could lead to similar CR/CRi rates with slightly shorter median OS than CPX-351.

This retrospective study investigated outcomes of 404 patients with relapsed/refractory (R/R) FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) acute myeloid leukemia (AML) enrolled in the PETHEMA registry, pre-approval of tyrosine kinase inhibitors. Most patients (63%) had received first-line intensive therapy with 3 + 7. Subsequently, patients received salvage with intensive therapy (n = 261), non-intensive therapy (n = 63) or supportive care only (n = 80). Active salvage therapy (i.e., intensive or non-intensive therapy) resulted in a complete remission (CR) or CR without hematological recovery (CRi) rate of 42%. More patients achieved a CR/CRi with intensive (48%) compared with non-intensive (19%) salvage therapy (p < 0.001). In the overall population, median overall survival (OS) was 5.5 months; 1- and 5-year OS rates were 25% and 7%. OS was significantly (p < 0.001) prolonged with intensive or non-intensive salvage therapy compared with supportive therapy, and in those achieving CR/CRi versus no responders. Of 280 evaluable patients, 61 (22%) had an allogeneic stem-cell transplant after they had achieved CR/CRi. In conclusion, in this large cohort study, salvage treatment approaches for patients with FLT3-ITD mutated R/R AML were heterogeneous. Median OS was poor with both non-intensive and intensive salvage therapy, with best long-term outcomes obtained in patients who achieved CR/CRi and subsequently underwent allogeneic stem-cell transplant.