A real-world analysis of clinical outcomes in AML with myelodysplasia-related changes: a comparison of ICC and WHO-HAEM5 criteria.

ABSTRACT: The proposed fifth edition of the World Health Organization classification of hematolymphoid tumors (WHO-HAEM5) and International Consensus Classification (ICC) provide different definitions of acute myeloid leukemia with myelodysplasia-related genetics (AML-MR). We conducted a retrospective study which included a cohort of 432 patients, with 354 patients fulfilling WHO-HAEM5 criteria for WHO-AML-MR or 276 patients fulfilling ICC criteria for ICC-AML-MR by gene mutation or cytogenetics (ICC-AML-MR-M/CG). The clinicopathological features were largely similar, irrespective of the classification used, except for higher rates of complex karyotype, monosomy 17, TP53 mutations, and fewer RUNX1 mutations in the WHO-AML-MR group. TP53 mutations were associated with distinct clinicopathological features and dismal outcomes (hazard ratio [HR], 2.98; P < .001). ICC-AML-MR-M/CG group had superior outcome compared with the WHO-AML-MR group (HR, 0.80, P = .032), largely in part due to defining TP53 mutated AML as a standalone entity. In the intensively-treated group, WHO-AML-MR had significantly worse outcomes than AML by differentiation (HR, 1.97; P = .024). Based on ICC criteria, ICC-AML-MR-M/CG had more inferior outcomes compared to AML not otherwise specified (HR, 2.11; P = .048 and HR, 2.55; P = .028; respectively). Furthermore, changing the order of genetic abnormalities defining AML-MR (ie, by gene mutations or cytogenetics) did not significantly affect clinical outcomes. ICC-AML-MR-M/CG showed similar outcomes regardless of the order of assignment. We propose to harmonize the 2 classifications by excluding TP53 mutations from WHO-HAEM5 defined AML-MR group and combining AML-MR defined by gene mutations and cytogenetics to form a unified group.

AML with CEBPA mutations: A comparison of ICC and WHO-HAEM5 criteria in patients with 20% or more blasts.

AML with CEBPA mutation and AML with in-frame bZIP CEBPA mutations define favorable-risk disease entities in the proposed 5th edition of the World Health Organization Classification (WHO-HAEM5) and the International Consensus Classification (ICC), respectively. However, the impact of these new classifications on clinical practice remains unclear. We sought to assess the differences between the ICC and WHO-HAEM5 for AML with CEBPA mutation. 741 AML patients were retrospectively analyzed. Cox proportional-hazard regression was used to identify factors predictive of outcome. A validation cohort from the UK-NCRI clinical trials was used to confirm our findings. 81 (11%) AML patients had CEBPA mutations. 39 (48%) patients met WHO-HAEM5 criteria for AML with CEBPA mutation, among which 30 (77%) had biallelic CEBPA mutations and 9 (23%) had a single bZIP mutation. Among the 39 patients who met WHO-HAEM5 criteria, 25 (64%) also met ICC criteria. Compared to patients only meeting WHO-HAEM5 criteria, patients with in-frame bZIP CEBPA mutations (ie. meeting both WHO-HAEM5 and ICC criteria) were younger, had higher bone marrow blast percentages and CEBPA mutation burden, infrequently harboured 2022 ELN high-risk genetic features and co-mutations in other genes, and had superior outcomes. The associations in clinicopathological features and outcomes between the CEBPA-mutated groups were validated in the UK-NCRI cohort. Our study indicates that in-frame bZIP CEBPA mutations are the critical molecular aberrations associated with favorable outcomes in AML patients treated with curative intent chemotherapy. Compared to WHO-HAEM5, the ICC identifies a more homogenous group of CEBPA-mutated AML patients with favorable outcomes.

Teaching number skills and concepts with Numicon materials.

This paper discusses the use of Numicon number teaching materials with children with Down syndrome. The theory underlying the design of the materials is discussed, the teaching approach and methodology are described and evidence supporting effectiveness is outlined.

Adrenergic receptors in the ptotic human eyelid: correlation with phenylephrine testing and surgical success in ptosis repair.

PURPOSE: To investigate the relationship between adrenergic receptors in Müller muscle and response to phenylephrine testing in patients undergoing ptosis surgery. This study also compares outcomes of Fasanella and Putterman approaches to posterior ptosis repair. METHODS: Prospective analysis of 71 patients undergoing posterior ptosis surgery. Eyelid height was measured before and after phenylephrine. Müller muscle was examined for alpha-1D, alpha-2C, beta-1, and beta-2 receptors. Specimens were graded on receptor staining intensity. Patients were seen 1 week and 6 weeks following surgery. Surgical outcomes were scored on a scale of 1 (most favorable) to 3 (least favorable). RESULTS: Adrenergic receptors were found in decreasing order: alpha-1D, beta-1, alpha-2C, and beta-2. Receptor grade significantly predicted eyelid height for alpha-2C receptors (p = .03). Mean outcome scores for 36 Putterman (1.10) and 35 Fasanella (1.27) procedures were not significantly different. CONCLUSIONS: Alpha 1D, alpha-2C, and beta-2 receptors are documented within human Müller muscle. Human eyelid elevation response to phenylephrine is inversely related to the amount of alpha-2C receptor staining in Müller muscle. Fasanella and Putterman procedures have equal outcomes, independent of adrenergic receptors.