{"doi":"10.1002/ajh.27465","title":"White blood cell count levels are associated with inflammatory response and constitute independent outcome predictors in adult patients with acute myeloid leukemia aged &lt;60 years","abstract":"Acute myeloid leukemia (AML) is a biologically and clinically heterogenous disease with diverse genetic abnormalities1-6 and a wide-ranging white blood cell counts (WBC) at diagnosis.1 The 2022 European LeukemiaNet (ELN) genetic-risk classification incorporates cytogenetic and selected molecular alterations to define Favorable, Intermediate, and Adverse genetic-risk groups providing valuable prognostic information.1 Pretreatment WBC levels are also a main prognostic factor for patients with AML;7, 8 however, there are no standardized WBC-associated groups that improve prognostication for younger patients. de Jonge et al.9 first investigated the impact of WBC on outcome of AML patients harboring NPM1 mutations and FLT3 internal tandem duplications (FLT3-ITD) that were divided into three WBC groups: <20 000/μL, WBC 20 000/μL–100 000/μL, and ≥100 000/μL. We decided to build upon this previous work by analyzing a larger, clinically and molecularly well-characterized cohort of 1121 younger (aged <60 years) adults with de novo AML to define clinically relevant WBC level groups and determine their potential independent prognostic impact and associations with gene-expression profiles. We defined three WBC groups: low (<10 000/μL, n = 298 patients), intermediate (10 000–49 999/μL, n = 488), and high (≥50 000/μL, n = 335). These groups were chosen because there was no correlation with an observable steady decrease in any analyzed outcome endpoint, including disease-free (DFS), event-free (EFS), or overall (OS) survival, with WBC increasing above 50 000/μL by 10 000/μL increments, nor were there any linear changes in endpoints associated with WBC decreasing below 10 000/μL in 1000/μL increments across the entire cohort (Figure S1A,B). All patients were similarly treated with a cytarabine/anthracycline based induction on frontline Cancer and Leukemia Group B (CALGB)/Alliance for Clinical Trials in Oncology (Alliance) protocols, with details of CALGB treatment protocols provided in the Data S1. No patient included in the analysis received an allogeneic hematopoietic stem-cell transplantation (HSCT) in first complete remission (CR), and patients who underwent an allogeneic HSCT off-study were not included because of incomplete or missing follow-up information. All patients were enrolled on CALGB 8461 (cytogenetic studies), CALGB 9665 (leukemia tissue bank), and CALGB 20202 (molecular studies) companion protocols, with further treatment details provided in the Data S1. The mutational status of 80 total protein-coding genes was determined centrally at The Ohio State University by targeted amplicon sequencing using the MiSeq platform (Illumina)6 and further detailed in the Data S1. Analysis of differentially expressed genes within each WBC group was done on peripheral blood samples via total transcriptome RNAseq with subsequent gene set enrichment analyses (GSEA) via Hallmark/Kegg pathways of 40% of our entire cohort. Clinical endpoints were defined according to generally accepted criteria.1 Baseline characteristics were compared using the Fisher's exact and Wilcoxon rank-sum tests for categorical and continuous variables, respectively.10 Estimated probabilities of DFS and OS were calculated using the Kaplan–Meier method,11 and the log-rank test evaluated differences between survival distributions. Multivariable logistic regression models were generated for attainment of CR, and multivariable proportional hazards models were constructed for DFS and OS using a limited backward elimination procedure, with variables significant at α = 0.2 from the univariable analyses considered for multivariable analyses. All analyses were performed by the Alliance Statistics and Data Center on a database locked on June 9, 2020 using SAS 9.4 and TIBCO Spotfire S + 8.2. Pretreatment patient characteristics are shown in Table S1. The median age for the three WBC groups (low, intermediate, and high) was similar (46, 44, and 43 years, respectively), and 55% of patie","journal":"American Journal of Hematology","year":2024,"id":481455,"datarank":0.12427252154851123,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.020300444464519417,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.020300444464519417,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":1,"citers_with_citation_signal":1,"citers_with_endowment":1,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9605,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT00048958","NCT00899223","NCT00900224"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":295283,"name":"Deedra Nicolet","orcid":"0000-0001-7796-0251","position":1,"is_corresponding":false},{"id":295280,"name":"Krzysztof Mrózek","orcid":"0000-0002-1408-5063","position":2,"is_corresponding":false},{"id":258663,"name":"Christopher J. Walker","orcid":"0000-0002-1819-7388","position":3,"is_corresponding":false},{"id":295288,"name":"James S. Blachly","orcid":"0000-0002-4275-5562","position":4,"is_corresponding":false},{"id":296788,"name":"Jessica Kohlschmidt","orcid":null,"position":5,"is_corresponding":false},{"id":295287,"name":"Shelley Orwick","orcid":"0000-0002-4537-1409","position":6,"is_corresponding":false},{"id":295289,"name":"Andrew J. Carroll","orcid":"0000-0001-9844-730X","position":7,"is_corresponding":false},{"id":305983,"name":"Richard A. Larson","orcid":"0000-0001-9168-3203","position":8,"is_corresponding":false},{"id":295290,"name":"Jonathan E. Kolitz","orcid":"0000-0003-2700-4784","position":9,"is_corresponding":false},{"id":261015,"name":"Bayard L. Powell","orcid":null,"position":10,"is_corresponding":false},{"id":34476,"name":"Richard M. Stone","orcid":"0000-0002-7526-2633","position":11,"is_corresponding":false},{"id":511547,"name":"John C. Byrd","orcid":"0000-0002-8778-1000","position":12,"is_corresponding":false},{"id":295293,"name":"Ann‐Kathrin Eisfeld","orcid":"0000-0001-6442-1419","position":13,"is_corresponding":false},{"id":295284,"name":"Alice S. Mims","orcid":"0000-0002-8971-2199","position":14,"is_corresponding":false},{"id":1037071,"name":"Michael Ozga","orcid":"0000-0002-7361-9846","position":0,"is_corresponding":true}],"reference_count":19,"raw_metadata":null,"created_at":"2026-07-19T02:07:10.067421Z","pmid":"39283025","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}