Hemato

Acute myeloid leukemia (AML) is predominantly a disease of older adults, with a median age at diagnosis of 68–72 years. Management in this population is complicated by adverse cytogenetic and molecular features, higher rates of secondary disease, and patient-specific factors such as comorbidity and frailty. This narrative review synthesizes the current evidence on risk stratification and treatment of AML in adults aged 60 years and older, with dedicated attention to patients aged 60–75 (“fit” older adults) and those older than 75, including octogenarians. The VIALE-A trial established venetoclax plus azacitidine as standard of care for patients ineligible for intensive chemotherapy (composite complete remission 66.4%; median overall survival 14.7 vs. 9.6 months with azacitidine alone). For fit adults aged 60–75, the choice between intensive chemotherapy and venetoclax-based regimens remains under active investigation, with emerging randomized data suggesting comparable outcomes and a possible advantage for venetoclax-based approaches in adverse-risk disease. Risk stratification has evolved beyond the 2022 European LeukemiaNet (ELN) classification, which was developed in intensively treated cohorts; the 2024 ELN genetic risk classification for less-intensive therapy now provides a framework specific to this population. TP53-mutated AML, including multi-hit disease, remains the dominant unmet need across all treatment modalities. Advances in reduced-intensity conditioning have expanded transplant eligibility into the seventh and eighth decades, and molecularly targeted approaches, including FLT3, IDH1/2, and menin inhibitors, are reshaping frontline and relapsed/refractory therapy. This review covers epidemiology, risk stratification, treatment stratified by age, fitness, and genetic subgroup, the role of transplantation and maintenance therapy, and the limitations of the current evidence base for this heterogeneous population.

Emperipolesis, a cell-in-cell phenomenon, involves a viable cell being transiently internalized within another cell’s cytoplasm from which it can exit without damaging either cell. In this report, we discuss the rarity of the emperipolesis of erythrocytes and erythroblasts, instead of the more commonly observed neutrophils. We report the case of a 52-year-old Chinese male who presented with pancytopenia and 33% blasts. Multiple mutations were revealed, including DNMT3A K826R, RUNX1 F396fs159, BCOR Q1208fs8, BCORL1 S575*, and PHF6 H302R. The patient was diagnosed with acute myeloid leukemia, myelodysplasia-related changes (AML-MR), and was treated with azacitidine and venetoclax, followed by daunorubicin and cytarabine (DA 3+7). This case highlights the rare occurrence of emperipolesis involving erythroid cells in AML-MR. We conducted a literature review exploring emperipolesis using PubMed, with search terms consisting of “emperipolesis”, “megakaryocytes”, “erythrocyte”, “erythroblast”, “neutrophil” and “lymphocyte”. A total of 24 articles that observed erythroid emperipolesis were referenced in this review, including 7 relevant case reports/series.

Background/Objectives: Patients receiving allogeneic hematopoietic stem cell transplantation (alloHCT) for acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) are at high risk for severe disease and treatment-related complications and toxicities. Pharmacogenetic studies suggest that genetic variants can alter the response to several drugs critical to alloHCT outcomes, including tacrolimus and cyclophosphamide, potentially impacting toxicity and treatment outcomes. Methods: To assess the frequency of pharmacogenetic variants in AML/ALL patients undergoing alloHCT, we used a validated 11-gene pharmacogenetic panel in an exploratory descriptive study. We retrospectively genotyped 142 AML/ALL patients including two atypical chronic myeloid leukemia (aCML) patients, ≥18 years, who underwent alloHCT at our center between January 2020 and June 2024. Results obtained from 470 individuals in the Lifelines NEXT population cohort were used as controls. Results: Almost all patients carried at least one pharmacogenetic variant (97.2%), with a mean of 3.2 (standard deviation = 1.5) variants per patient. Variants known to influence tacrolimus metabolism (CYP3A4 and CYP3A5) were present in 26.8% of patients. Variants known to influence cyclophosphamide metabolism (CYP2B6, CYP2C9, CYP2C19) were present in 81.7% of patients. Variant frequencies did not significantly differ from controls. Conclusions: Actionable pharmacogenetic variants are highly prevalent in alloHCT-recipients. Future studies should investigate whether genotype-guided drug selection and dosing could improve outcomes in alloHCT recipients.