Identification of red blood cell distribution width as a prognostic factor in acute myeloid leukemia.

Many prognostic factors have been identified in acute myeloid leukemia (AML). In this study, we investigated novel prognostic biomarkers using machine learning and Cox regression models in a prospective cohort of 591 patients with AML and tried to identify potential therapeutic targets based on transcriptomic data. We found that elevated red blood cell distribution width (RDW) at diagnosis was an adverse prognostic factor for AML, independent of the 2022 European LeukemiaNet (ELN2022) genetic risk. As a continuous variable, higher RDW was associated with shorter overall survival (OS) (hazard ratio [HR] 1.087, 95% confidence interval [CI] 1.036-1.139, p < 0.001) and event-free survival (EFS) (HR 1.078, 95% CI 1.033-1.124, p < 0.001). Elevated RDW returned to normal after consolidation therapy, which indicated that leukemia cells resulted in abnormal RDW. We further investigated the relationship between RDW and transcriptome in another cohort of 191 patients with AML and public datasets using gene set enrichment analysis (GSEA) and cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT). We found that patients in the high-RDW group were significantly enriched in the positive regulation of erythroid differentiation and inflammation-related pathways. Finally, we identified the inflammation-associated gene IL12RB2 and verified its prognostic relevance with patients with AML in public databases, suggesting it as a potential therapy target.

Immunophenotype distinctions of CEBPA mutation subtypes in acute myeloid leukemia.

INTRODUCTION: Acute myeloid leukemia (AML) patients with CEBPA double mutation (CEBPAdm ) were associated with distinct immunophenotypes and prognosis. Recently, both International Consensus Classification (ICC) and World Health Organization (WHO) classifications incorporated BZIP single mutations (CEBPAsmBZIP ) into the favorable risk group. However, the immunophenotypes of CEBPAsmBZIP mutations have not been characterized, especially when compared with the immunophenotypes of CEBPAdm . METHODS: Retrospectively, we investigated and compared the immunophenotypes of AML with CEBPA mutations. Randomforest model and XGBoost algorithm were used to set up a scoring system based on the immunophenotypes of those patients. RESULTS: In a total of 967 AML patients: 218 were CEBPAdm (198 consisted of mutations in the BZIP region [CEBPAdmBZIP ], 20 were double mutations outside BZIP region [CEBPAdm-woBZIP ]), 117 were CEBPAsm (54 CEBPAsmBZIP and 63 were single mutations outside BZIP region [CEBPAsm-woBZIP ]) and the others were wildtype CEBPA (CEBPAwt ). Patients with CEBPAdmBZIP , CEBPAdm-woBZIP and CEBPAsmBZIP shared the distinct immunophenotype of CD7+ CD34+ MPO+ HLA-DR+ CD19- , in contrast to patients with CEBPAsm-woBZIP and CEBPAwt who showed reduced expression of CD7, HLA-DR, MPO, CD34 and a higher expression of CD19. Based on these immunophenotypes, we developed a scoring system to preemptively identify AML with CEBPAsmBZIP and CEBPAdm and validated it internally and externally. CONCLUSIONS: AML with CEBPAdmBZIP , CEBPAdm-woBZIP , and CEBPAsmBZIP shared similar immunophenotypic profiles, whereas profoundly differed from the CEBPAsm-woBZIP and CEBPAwt AML.

A pilot intervention of using a mobile health app (ONC Roadmap) to enhance health-related quality of life in family caregivers of pediatric patients with cancer.

Background: The Roadmap mobile health (mHealth) app was developed to provide health-related quality of life (HRQOL) support for family caregivers of patients with cancer. Methods: Eligibility included: family caregivers (age ≥18 years) who self-reported as the primary caregiver of their pediatric patient with cancer; patients (age ≥5 years) who were receiving cancer care at the University of Michigan. Feasibility was calculated as the percentage of caregivers who logged into ONC Roadmap and engaged with it at least twice weekly for at least 50% of the 120-day study duration. Feasibility and acceptability was also assessed through a Feasibility and Acceptability questionnaire and the Mobile App Rating Scale to specifically assess app-quality. Exploratory analyses were also conducted to assess HRQOL self- or parent proxy assessments and physiological data capture. Results: Between September 2020-September 2021, 100 participants (or 50 caregiver-patient dyads) consented and enrolled in the ONC Roadmap study for 120-days. Feasibility of the study was met, wherein the majority of caregivers (N=32; 65%) logged into ONC Roadmap and engaged with it at least twice weekly for at least 50% of the study duration (defined a priori in the Protocol). The Feasibility and Acceptability questionnaire responses indicated that the study was feasible and acceptable with the majority (>50%) reporting Agree or Strongly Agree with positive Net Favorability [(Agree + Strongly Agree) - (Disagree + Totally Disagree)] in each of the domains (e.g., Fitbit use, ONC Roadmap use, completing longitudinal assessments, engaging in similar future study, study expectations). Improvements were seen across the majority of the mental HRQOL domains across all groups; even though underpowered, there were significant improvements in caregiver-specific aspects of HRQOL and anxiety and in depression and fatigue for children (ages 8-17 years), and a trend toward improvement in depression for children ages 8-17 years and in fatigue for adult patients. Conclusions: This study supports that mHealth technology may be a promising platform to provide HRQOL support for caregivers of pediatric patients with cancer. Importantly, the findings suggest that the study protocol was feasible, and participants were favorable to participate in future studies of this intervention alongside routine cancer care delivery.