Fitness in acute myeloid leukemia, state of the art and future directions

Acute Myeloid Leukemia (AML) is a complex disease whose outcome can be variably influenced by several clinical and biological factors. Although there is still no consensus on how to integrate these elements to best guide treatment choice, multiparametric models, commonly called fitness scores, have been developed to evaluate each patient’s ability to tolerate therapies. These models consider various risk factors, including disease biology, comorbidities, physical and cognitive function. To date, several scoring systems can be used to categorize patients on their fitness for intensive or non-intensive therapies. However, existing tools mainly focus on identifying patients suitable for conventional intensive chemotherapy and fail to address the complexities of less-fit patients who might benefit from innovative intensive, less-intensive, and even maintenance strategies. As treatment landscapes are in constant evolution, identifying intermediate level of fitness through recalibration of existing scores or development of new ones should be prioritized. Considering all the above, this review aims to report on the state of the art of fitness assessment in AML and discuss possible future directions on this topic

Time for Dynamic Assessment of Fitness in Acute Myeloid Leukemia

Informed treatment decision-making in acute myeloid leukemia (AML) requires a comprehensive evaluation of all clinical and biological features that may affect the outcome with any given type or intensity of therapy [...

Thickness-dependent crystallization on thermal anneal for titania/silica nm-layer composites deposited by ion beam sputter method.

Crystallization following thermal annealing of thin film stacks consisting of alternating nm-thick titania/silica layers was investigated. Several prototypes were designed, featuring a different number of titania/silica layer pairs, and different thicknesses (in the range from 4 to 40 nm, for the titania layers), but the same nominal refractive index (2.09) and optical thickness (a quarter of wavelength at 1064 nm). The prototypes were deposited by ion beam sputtering on silicon substrates. All prototypes were found to be amorphous as-deposited. Thermal annealing in air at progressive temperatures was subsequently performed. It was found that the titania layers eventually crystallized forming the anatase phase, while the silica layers remained always amorphous. However, progressively thinner layers exhibited progressively higher threshold temperatures for crystallization onset. Accordingly it can be expected that composites with thinner layers will be able to sustain higher annealing temperatures without crystallizing, and likely yielding better optical and mechanical properties for advanced coatings application. These results open the way to the use of materials like titania and hafnia, that crystallize easily under thermal anneal, but ARE otherwise promising candidate materials for HR coatings necessary for cryogenic 3rd generation laser interferometric gravitational wave detectors

Predictors of Early Thrombotic Events in Adult Patients with Acute Myeloid Leukemia: A Real-World Experience

Information regarding the incidence and the prognostic impact of thrombotic events (TE) in non-promyelocytic acute myeloid leukemia (AML) is sparse. Although several risk factors associated with an increased risk of TE development have been recognized, we still lack universally approved guidelines for identification and management of these complications. We retrospectively analyzed 300 consecutive patients with newly diagnosed AML. Reporting the incidence of venous TE (VTE) and arterial TE (ATE) was the primary endpoint. Secondarily, we evaluated baseline patient- and disease-related characteristics with a possible influence of VTE-occurrence probability. Finally, we evaluated the impact of TE on survival. Overall, the VTE incidence was 12.3% and ATE incidence was 2.3%. We identified three independent predictors associated with early-VTE: comorbidities (p = 0.006), platelets count >50x10e9/L (p = 0.006), and a previous history of VTE (p = 0.003). Assigning 1 point to each variable, we observed an overall cumulative incidence of VTE of 18.4% in the high-risk group (>2 points) versus 6.4% in the low-risk group (0–1 point), log-rank = 0.002. Overall, ATE, but not VTE, was associated with poor prognosis (p < 0.001). In conclusion, TE incidence in AML patients is not negligible. We proposed an early-VTE risk score that could be useful for a proper management of VTE prophylaxis

Pulmonary function testing for fitness assessment in asymptomatic adults with newly diagnosed acute myeloid leukemia

Not available

Case report: A Saprochaete clavata (Magnusiomyces clavatus) severe infection effectively treated with granulocyte transfusion in a young patient with myeloid sarcoma

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

Measurable Residual Disease (MRD) as a Surrogate Efficacy-Response Biomarker in AML

In acute myeloid leukemia (AML) many patients experience relapse, despite the achievement of morphological complete remission; therefore, conventional morphologic criteria are currently considered inadequate for assessing the quality of the response after treatment. Quantification of measurable residual disease (MRD) has been established as a strong prognostic marker in AML and patients that test MRD negative have lower relapse rates and better survival than those who test positive. Different techniques, varying in their sensitivity and applicability to patients, are available for the measurement of MRD and their use as a guide for selecting the most optimal postremission therapy is an area of active investigation. Although still controversial, MRD prognostic value promises to support drug development serving as a surrogate biomarker, potentially useful for accelerating the regulatory approval of new agents. In this review, we will critically examine the methods used to detect MRD and its potential role as a study endpoint

Use of Primary Prophylaxis with G-CSF in Acute Myeloid Leukemia Patients Undergoing Intensive Chemotherapy Does Not Affect Quality of Response

Background/Objectives: The objective of our study was to evaluate the safety and efficacy of granulocyte colony-stimulating factor (G-CSF) as primary prophylaxis in adult patients with acute myeloid leukemia (AML) undergoing intensive chemotherapy. Methods: We retrospectively analyzed 112 AML patients treated with intensive chemotherapy at Fondazione Policlinico Tor Vergata in Rome between January 2014 and March 2024. Patients were divided into G-CSF and non-G-CSF (nG-CSF) groups. We assessed the incidence of neutropenia, its severity and duration; duration of hospitalization and its costs; incidence of febrile neutropenia (FN) and septic shock; duration of antibiotic therapy (ABT) and antifungal therapy (AFT); complete remission (CR) rates; measurable residual disease (MRD) status; relapse rates; and outcomes. Results: G-CSF administration significantly reduced the duration of neutropenia (median 14 vs. 18 days, p < 0.05) and length of hospitalization (median 28 vs. 35 days, p < 0.05), in both induction and consolidation therapy. There were no significant differences in CR rates (73% vs. 67%, p = 0.64), MRD negativity achievement (52% vs. 48%, p = 0.68), leukemia relapse rates (43% vs. 62%, p = 0.14), or overall survival (OS) (median 16.7 vs. 12.3 months, p = 0.3) between G-CSF and nG-CSF groups. Thanks to a shorter hospitalization, the use of G-CSF led to €300,000 in savings over the last 4 years. Conclusions: Our findings support the safety of G-CSF in AML patients, demonstrating no adverse impact on treatment response. G-CSF abbreviated the duration of neutropenia and hospitalization, highlighting its potential clinical and cost-effective role in AML treatment