{"doi":"10.1002/hon.70093_120","title":"120 | DETECTION OF INTRATUMORAL MICROORGANISMS AND THEIR IMPACT ON OUTCOMES IN UNTREATED DIFFUSE LARGE B‐CELL LYMPHOMA","abstract":"Introduction: In DLBCL, the tumor microenvironment (TME) is a critical component of lymphoma biology and impacts patient outcomes. Intratumoral microorganisms (IMS) constitute part of the TME in solid tumors and tend to localize in niches, interacting with the TME and influencing response to therapy and outcomes. We hypothesize that similar findings could be observed in lymphoma. Methods: Targeted next-generation sequencing (NGS) was performed on pre-treatment samples from 266 patients (pts) with DLBCL who received first-line therapy at our institution. The control group comprised 71 lymph node samples from pts with suspected hematologic disorders where the same NGS revealed no mutations. Microbial reads from regions that do not align with the human reference genome were analyzed (Elkrief JCO 2024). Several databases were referenced to exclude contaminations, and IMS were deemed positive if a minimal number of reads was present based on the literature. These results were coupled with data on baseline characteristics, treatment, and outcomes from our clinical database. We compared variables with Fisher’s test, the t-test, and multivariable Cox regression analysis for survival for IMSs present in > 10% of the samples. Multiple test correction was performed with FDR. Results: Median age at diagnosis was 62 (18–89), 55% were male, 49% IPI score of 0–2, 26% had B-symptoms. Histology was germinal center (GC) derived (33%), non-GC (30%), high grade (HG)BCL (18%), not otherwise specified (14%) and transformed DLBCL (5%). Median number of IMS per DLBCL sample was 8 (min 0–max 316) versus 3 (min 0 max 90) in the controls, p = 0.018. No difference in IMS × sample was found between lymph node versus extranodal biopsies. IMS × sample was not associated with age, sex, histology, IPI score, B-symptoms, nor treatment response, PFS, or OS. Detection of Rothia, Actinomyces, Neisseria, Rhodococcus, Escherichia, Prevotella, and Mycolicibacterium was more frequent in DLBCL compared to controls. Prevotella (72/266, 27%) was associated with improved PFS (log-rank p = 0.002) and a tendency towards improved OS (log-rank p = 0.09). Multivariable COX regression for the association of Prevotella with PFS controlling for IPI score, histology, and age at diagnosis, demonstrated an HR of 0.58 (95% CI: 0.34–0.99, p = 0.048, FDR q = 1.04), while it was not significantly associated with HGBCL, IPI, B-symptoms, age, sex, treatment response or histology. Enterococcus (16%), which was detected in similar levels in the controls, was associated with poorer OS (p = 0.017) and tendency over poorer PFS (p = 0.061) and confirmed on COX regression (HR OS 1.95, 95% CI: 1.06–3.61, p = 0.033, FDR q = 0.4). Conclusions: Our study of IMS on pre-treatment samples of DLBCL suggests an increased incidence of IMA detection in DLBCL, and a potential association with disease outcome. Further studies in larger independent cohorts are needed to confirm these results and evaluate the interactions of IMS with the DLBCL TME. Keywords: non-Hodgkin; microenvironment; aggressive B-cell non-Hodgkin lymphoma No potential sources of conflict of interest.","journal":"Hematological Oncology","year":2025,"id":568664,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9518,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":55986,"name":"Chad Vanderbilt","orcid":"0000-0002-8114-0237","position":1,"is_corresponding":false},{"id":457319,"name":"Teng Fei","orcid":"0000-0001-7888-1715","position":2,"is_corresponding":false},{"id":1473816,"name":"Ticiane Henriques Santa Rita","orcid":null,"position":3,"is_corresponding":false},{"id":1473817,"name":"A. Rivas Delgado","orcid":null,"position":4,"is_corresponding":false},{"id":951052,"name":"Annie Qiu","orcid":"0000-0001-8037-1589","position":5,"is_corresponding":false},{"id":930398,"name":"Michelle Okwali","orcid":null,"position":6,"is_corresponding":false},{"id":1473509,"name":"Manpreet Uppal","orcid":"0000-0002-5448-3939","position":7,"is_corresponding":false},{"id":55979,"name":"Roni Shouval","orcid":"0000-0001-9827-8032","position":8,"is_corresponding":false},{"id":1473818,"name":"A. P. Boardman","orcid":null,"position":9,"is_corresponding":false},{"id":248510,"name":"Philip Caron","orcid":null,"position":10,"is_corresponding":false},{"id":262218,"name":"Kevin A. David","orcid":"0000-0001-7415-0376","position":11,"is_corresponding":false},{"id":275371,"name":"Zachary D. Epstein‐Peterson","orcid":"0000-0002-5942-2502","position":12,"is_corresponding":false},{"id":1473819,"name":"L. Falchi","orcid":null,"position":13,"is_corresponding":false},{"id":246206,"name":"Paul A. 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Arcila","orcid":"0000-0001-5824-6554","position":32,"is_corresponding":false},{"id":225648,"name":"Jonathan U. Peled","orcid":"0000-0002-4029-7625","position":33,"is_corresponding":false},{"id":281051,"name":"Megan S. Lim","orcid":"0000-0002-0415-2867","position":34,"is_corresponding":false},{"id":1473821,"name":"G. Salles","orcid":null,"position":35,"is_corresponding":false},{"id":233575,"name":"Paola Ghione","orcid":"0000-0001-6986-7954","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T02:56:55.795846Z","pmid":null,"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":[]}