The increasing knowledge of molecular genetics of acute myeloid leukemia (AML) urged the update of previous diagnostic and prognostic schemes, which resulted in the development, in 2022, of the World Health Organization (WHO), the International Consensus Classification (ICC) and the new European LeukemiaNet (ELN) recommendations. We aimed to provide a real-world application of the new models, to unravel differences and similarities, and to test their implementation in clinical AML diagnosis. A total of 1001 patients diagnosed with AML were re-classified according to the new schemes. The overall diagnostic changes between the WHO 2016, compared to WHO 2022 and ICC classifications were 22.8% and 23.7%, respectively, with a 13.1% difference in patients' distribution between ICC and WHO 2022. The 2022 ICC "not otherwise specified" and WHO "defined by differentiation" AML categories shrank as compared to WHO 2016 (24.1% and 26.8% respectively, vs 38.7%), particularly due to an expansion of the myelodysplasia (MDS)-related group. Of 397 patients with a MDS-related AML according to the ICC, 55.9% were defined by the presence of a MDS-related karyotype. The overall re-stratification between ELN 2017 and 2022 was 12.9%. The 2022 AML classifications led to a significant improvement of diagnostic schemes. In the real-world setting, conventional cytogenetics, usually rapidly available and less expensive than molecular characterization, stratified 56% of secondary AML, still maintaining a powerful diagnostic role. Considering the similarities between WHO and ICC diagnostic schemes, a tentative to generate a unified model is desirable.

Abstract. Background: Colonization by multidrug-resistant organisms (MDRO) is a frequent complication in hematologic departments, which puts patients at risk of life-threatening bacterial sepsis. Fever of unknown origin (FUO) is a condition related to the delivery of chemotherapy in hematologic malignancies, in which the use of antibiotics is debated. The incidence, risk factors, and influence on the outcome of these conditions in patients with acute myeloid leukemia (AML) are not clearly defined.Methods: We retrospectively analyzed 132 consecutive admissions of non-promyelocytic AML patients at the Hematology Unit of the University Tor Vergata in Rome between June 2019 and February 2022. MDRO swab-based screening was performed in all patients on the day of admission and once weekly after that. FUO was defined as fever with no evidence of infection.Results: Of 132 consecutive hospitalizations (69 AML patients), MDRO colonization was observed in 35 cases (26%) and resulted independently related to a previous MDRO colonization (p=0.001) and length of hospitalization (p=0.03). The colonization persistence rate in subsequent admissions was 64%. MDRO-related bloodstream infection was observed in 8 patients (23%) and correlated with grade III/IV mucositis (p=0.008) and length of hospitalization (p=0.02). FUO occurred in 68 cases (51%) and correlated with an absolute neutrophilic count <500μ/L at admission (0.04).Conclusion: In our experience, MDRO colonization is a frequent and difficult-to-eradicate condition that can arise at all stages of treatment. Prompt discharge of patients as soon as clinical conditions allow could limit the spread of MDRO. In addition, the appropriate use of antibiotics, especially in the case of FUO, and the contraction of hospitalization length, when feasible, are measures to tackle the further spread of MDRO.

Myeloid sarcoma is a hematologic malignancy consisting of extramedullary tissue involvement by myeloid blasts, usually considered as acute myeloid leukemia and treated accordingly. The disease itself, together with chemotherapy and disease-associated factors, may have an impact in increasing the risk of developing severe and frequently life-threatening infections. Herein, we describe the case of a patient with a right breast skin lesion, histologically diagnosed myeloid sarcoma, who developed a severe disseminated fungal infection by Saprochaete clavata (Magnusiomyces clavatus), during the first consolidation course of chemotherapy. Despite maximum antifungal therapy, the infection progressed and the fungus continued to be isolated until granulocyte transfusion therapy was initiated. Our experience suggests that patients with profound and long-lasting neutropenia could benefit from granulocyte transfusions as additional therapy in severe fungal infections resistant to broad-spectrum antimicrobial therapy.

Evolution of myeloproliferative neoplasms (MPN) to acute myeloid leukemia (AML) occurs in 2-10% of patients, whereas the reverse path from AML to MPN has been rarely reported. We herein present a 75-year-old woman with AML, in whom a JAK2-V617F positive polycythemia vera (PV) emerged during follow-up, 19 months from end of consolidation treatment. JAK2-V617F mutation screening retrospectively performed by Next Generation Sequencing (NGS) and JAK2 MutaScreen was negative on the bone marrow sample collected at AML diagnosis. However, using droplet digital PCR (ddPCR), we detected a minor JAK2-V617F mutated clone present at AML onset. A TET2 R550 mutated clone persisted at stable levels throughout the disease course. This case shows that a very small MPN clone masked at AML diagnosis may expand after treatment end, and be erroneously interpreted as MPN evolving from AML. Very sensitive techniques as ddPCR may help to unravel the true disease history in these cases.