Acute myeloid leukemia (AML) is a highly aggressive illness distinguished by the accumulation of abnormal hematopoietic precursors in both the bone marrow and peripheral blood. The prevalence of FLT3 gene mutations is high and escalates the probability of relapse and mortality. The survival rates for AML patients, particularly those over 65, are low. FLT3 mutation screening at diagnosis is mandatory, and FLT3 inhibitors are crucial in treating AML patients with mutations. There are two categories of FLT3 mutations: FLT3-ITD located in the juxtamembrane domain and FLT3-TKD in the tyrosine kinase domain. FLT3-ITD is the most common type, affecting nearly a quarter of patients, whereas FLT3-TKD only affects 6–8% of patients. FLT3 inhibitors are now crucial in treating AML patients with FLT3 mutations. When dealing with FLT3-mutated AML, the recommended course of treatment typically involves chemotherapy and midostaurin, followed by allogeneic hematopoietic cell transplantation (HCT) to maximize the likelihood of success. Maintenance therapy can lower the risk of relapse, and gilteritinib is a better option than salvage chemotherapy for relapsed or refractory cases. Clinical trials for new or combined therapies are the most effective approach. This review discusses treatment options for patients with FLT3-mutated AML, including induction chemotherapy and options for relapsed or refractory disease. Additional treatment options may become available as more studies are conducted based on the patient’s condition and susceptibility.

Myelodysplastic neoplasms represent a diverse group of clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis, peripheral cytopenias, and an inherent risk of progression to acute myeloid leukemia. Accurate risk assessment and patient stratification are critical to optimizing therapeutic approaches and clinical outcomes. In 2022, significant advancements reshaped both the classification and prognostic stratification of MDSs. The revised WHO Classification introduced crucial genetically defined subtypes, particularly those involving biallelic TP53 inactivation and SF3B1 mutations, shifting the emphasis from traditional morphology-based criteria to molecular ones. Simultaneously, morphological subtypes such as hypoplastic and hyperfibrotic MDSs were established as distinct entities with unique prognostic implications. At the same time, the introduction of the International Molecular Prognostic Scoring System (IPSS-M) provided a more precise prognostic stratification by integrating comprehensive molecular data alongside traditional clinical and cytogenetic parameters. Several validation studies have confirmed IPSS-M’s superior discriminative power compared to previous models, notably IPSS-R, improving predictions regarding overall survival and leukemia transformation. Nevertheless, practical considerations regarding the widespread application of IPSS-M have emerged, including concerns over economic feasibility and accessibility of advanced molecular testing methods, such as extensive Next-Generation Sequencing panels. This review synthesizes the recent literature and critical studies validating these classification and prognostic updates, discussing their clinical impact, practical considerations, and implications for targeted therapeutic strategies. By focusing on molecular pathogenesis, the latest classification systems and prognostic models promise significant advances in patient-specific management, setting the stage for future innovations in treatment and improved patient outcomes.

Introduction: Acute myeloid leukemia (AML) is a form of cancer originating from precursor cells within the bone marrow. Elderly patients with acute leukemia require a personalized approach, considering age, performance status, and comorbidities, to determine suitability for intensive treatment. Methods: We studied the results of intense chemotherapy in 46 elderly, fit individuals with AML at a cancer center in Romania from January 2017 to December 2023. Results: The study involved a cohort of 46 patients, including 22 men and 24 women. The research indicated that 89.1% of the patients were diagnosed with de novo acute leukemia. Most patients had an ECOG score of 0–1, with one patient scoring ≥2. HCT-CI > 4 was found in 21 patients (45.7%), while CCI > 4 was present in 38 patients (82.6%). After the induction phase, 25 patients (54.3%) achieved complete remission (CR); the relapse rate was 56.8%. Upon completion of the study, nine individuals (19.6%) were still alive. The overall survival duration ranged from 0 to 33 months, with a median survival time of 8 months (CI 5.0–11.0). Conclusions: When considering treatment options for elderly patients, the Eastern Cooperative Oncology Group (ECOG) Performance Status, as well as comorbidity indices such as the Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI) and the Charlson Comorbidity Index (CCI), have shown promising results in the literature, indicating their relevance in the decision-making process.

Background: Higher-risk myelodysplastic neoplasms (HR-MDS) are associated with poor survival and a substantial risk of leukemic transformation. Although azacitidine is a standard treatment in this setting, comparative real-world data remain limited. We evaluated the association between azacitidine exposure and clinical outcomes in patients with HR-MDS. Methods: We performed a retrospective single-center cohort study including 72 adults with HR-MDS, defined by the Revised International Prognostic Scoring System(IPSS-R) as High or Very High risk. Patients were categorized as azacitidine-treated (Aza, n = 44) or managed with best supportive care alone (No Aza, n = 28). Overall survival (OS) was defined from diagnosis to death from any cause. Progression-free survival (PFS) was defined as the time to acute myeloid leukemia transformation or death. Leukemic transformation (LT) was analyzed using Kaplan–Meier estimates and competing-risk cumulative incidence, with death without prior LT treated as a competing event. Univariable and multivariable Cox regression models were applied. Results: Azacitidine exposure was associated with longer OS compared with best supportive care, with a median OS of 13 vs.10 months and 24-month OS rates of 27% vs. 14% (p = 0.0239). PFS was also prolonged in the Aza group, with a median of 11 vs. 7 months (p = 0.0406). LT-related outcomes similarly favored azacitidine. In multivariable analyses, azacitidine remained independently associated with improved OS, PFS, and LT-related outcomes. IPSS-R Very High risk remained an adverse prognostic factor across endpoints, while a higher baseline bone marrow blast percentage independently predicted leukemic transformation. Conclusions: In this real-world HR-MDS cohort, azacitidine exposure was associated with improved survival outcomes and delayed leukemic transformation compared with best supportive care alone.

Background: Myelodysplastic syndromes are clonal hematopoietic disorders characterized by ineffective hematopoiesis and risk of progression to acute myeloid leukemia. Accurate prognostic stratification is essential to guide treatment, with several scoring systems in clinical use: IPSS, IPSS-R, and WPSS. Objective: We aimed to evaluate the prognostic accuracy of IPSS, IPSS-R, and WPSS in a real-world Romanian MDS cohort by comparing risk classifications with observed overall survival and progression-free survival. Methods: We conducted a retrospective analysis of 117 patients diagnosed with MDS treated in our clinic between 2018 and 2022. All patients had confirmed diagnoses based on bone marrow biopsy and cytogenetic testing. Data were used to assign risk categories based on IPSS, IPSS-R, and WPSS. Survival outcomes were analyzed using Kaplan–Meier curves and log-rank tests. Results: The median age of the cohort was 70 years; gender distribution was balanced. Transfusion dependence was present in 73.5%, and 49.6% had cytogenetic abnormalities. Overall, low-risk classification was assigned in 58.1% (IPSS), 38.5% (IPSS-R), and 38.5% (WPSS) of patients. Median OS was 20 months, and median PFS was 35 months. Although no statistically significant overall survival differences were observed across scoring systems, IPSS-R demonstrated a trend toward stronger prognostic discrimination in multivariable analysis. Reclassification of patients initially categorized as IPSS intermediate-1 revealed a significant survival impact: patients reclassified as lower-risk by IPSS-R and WPSS had a median OS of 67.5 months versus 15 months for those reclassified as higher-risk (IPSS-R: HR = 0.24; p = 0.0017; WPSS: HR = 0.26; p = 0.0031). Similarly, leukemic transformation occurred in 13.6% of reclassified lower-risk patients vs. 52.2% in higher-risk patients (IPSS-R: HR = 0.13; p = 0.0021; WPSS: HR = 0.12; p = 0.002), with a median PFS of 21 months in the higher-risk group. In multivariable Cox regression analysis, IPSS-R stratification remained a strong independent predictor for both OS (HR = 3.22; p = 0.000003) and PFS (HR = 4.77; p < 0.00001), while azacitidine treatment was associated with significantly improved survival (OS: HR = 0.43; p = 0.00002) and reduced risk of progression (PFS: HR = 0.36; p = 0.013).