Thrombosis in Myeloid Malignancies, from CHIP to AML.

The development of myeloid malignancies is a multi-step process starting from pre-malignant stages. Large-scale studies on clonal hematopoiesis of indeterminate potential (CHIP) identified this condition as a risk factor for developing hematologic malignancies, in particular myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). In parallel, CHIP was found to confer an enhanced thrombotic risk, in particular for cardiovascular diseases. In a similar fashion, in recent years, alongside their life-threatening features, increasing attention has been drawn toward thrombotic complications in myeloid malignancies. The purpose of this review is to gather growing body of evidence on incidence, pathogenesis and clinical impact of thrombosis in myeloid malignancies at every step of malignant progression, from CHIP to AML.

Applicability of 2022 classifications of acute myeloid leukemia in the real-world setting.

The increasing knowledge of molecular genetics of acute myeloid leukemia (AML) necessitated the update of previous diagnostic and prognostic schemes, which resulted in the development of the World Health Organization (WHO), the International Consensus Classification (ICC), and the new European LeukemiaNet (ELN) recommendations in 2022. We aimed to provide a real-world application of the new models, unravel differences and similarities, and test their implementation in clinical AML diagnosis. A total of 1001 patients diagnosed with AML were reclassified based on the new schemes. The overall diagnostic changes between the WHO 2016 and the 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 category sizes shrank when compared with that in WHO 2016 (24.1% and 26.8% respectively, vs 38.7%), particularly because of 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 restratification between ELN 2017 and ELN 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 scheme to generate a unified model is desirable.

Fever of Unknown Origin and Multidrug Resistant Organism Colonization in AML Patients.

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.

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.

An Polycythemia Vera Evolve from Acute Myeloid Leukemia? Report of a Case Showing a Simultaneous Minor JAK2 V617F Mutated Clone.

The evolution of myeloproliferative neoplasms (MPN) to acute myeloid leukemia (AML) occurs in 2-10% of patients, depending on the MPN subtype, treatment, and follow-up length. The reverse-path from AML to MPN has been rarely reported. We herein present a 75 years old woman with AML, in whom a JAK2-V617F positive polycythemia vera (PV) emerged during follow-up, 19 months from the 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 digital droplet PCR (ddPCR), we detected a minor JAK2 V617F mutated clone at AML onset. In addition, 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 such as ddPCR may help to unravel the true disease history in these cases.

Xenon anesthesia for awake craniotomy: safety and efficacy.

BACKGROUND: The asleep-awake-asleep (AAA) craniotomy is a technique that offers the opportunity of having a patient fully cooperative during the awake phase, and minimizes the possible discomfort, due to the asleep phase. The aim of this prospective observational study was to test the use of xenon in the first asleep phase of an AAA craniotomy, in patients undergoing craniotomy for brain tumor resection. METHODS: The data have been collected from 40 awake craniotomy procedures, performed in patients with cerebral tumor, treated with the AAA technique. Patients were treated with xenon during the asleep phase, and quality of mapping, complications and qualitative judgment of the experience given by the patients were recorded. RESULTS: The mapping was carried out as planned in 37 out of 40 cases. The doses of xenon administered during the first asleep phase of the anesthesia was 13±2 L. Time for awakening after xenon was switched off was 5±1 minute. A combination of xenon and regional anesthesia (with no need for additional systemic anesthetics) was adequate to accomplish craniotomy in 27/40 patients (67.5%). On the day after the operation, 37 patients recalled the testing procedure for mapping during the awake period, none had recollection of local anesthetic injections for regional anesthesia or sound associated with the neurosurgical drill. Five patients (12.5%) reported mild pain during tumor removal (VAS Score less than three). CONCLUSIONS: In this case series, xenon anesthesia was successfully used for the sedative phase of an awake craniotomy accomplished with an AAA approach.

Effects of propofol or sevoflurane anesthesia induction on hemodynamics in patients undergoing fiberoptic intubation for cervical spine surgery: A randomized, controlled, clinical trial.

BACKGROUND AND AIMS: In patients undergoing surgery for cervical myelopathy, induction of general anesthesia can induce systemic arterial hypotension that may worsen spinal cord hypoperfusion and precipitate spinal injury. In this randomized, controlled, clinical trial study, we compared the hemodynamic changes related to anesthesia induction with intravenous (IV) propofol- and sevoflurane-based inhalational induction in patients undergoing fiberoptic intubation for cervical spine surgery. MATERIAL AND METHODS: A total of 72 patients were studied. Hemodynamic effects were assessed measuring mean arterial pressure (MAP), and the echocardiographic evaluation of the left ventricular function. A Student's t-test with Bonferroni correction or Chi-squared test was used, when appropriate, to assess differences in hemodynamic (extent of MAP drop and incidence of episodes of severe arterial hypotension) and other variables (occurrence and duration of episodes of apnea). RESULTS: Patients assigned to total IV anesthetic approach had a lower MAP, and more significant changes in cardiac function compared to those who received the inhalational approach (68.1 ± 9.3 mmHg vs. 75.5 ± 10.3 mmHg; 25% vs. 5.5%). CONCLUSION: Anesthesia induction with both propofol or sevoflurane is safe and effective. However, total IV anesthesia induction is associated with more pronounced MAP drop which can worsen spinal cord hypoperfusion.