{"doi":"10.1158/2159-8290.cd-24-0719","title":"Nonselective β-Adrenergic Receptor Inhibitors Impair Hematopoietic Regeneration in Mice and Humans after Hematopoietic Cell Transplants","abstract":"Peripheral nerves promote mouse bone marrow regeneration by activating β2- and β3-adrenergic receptor signaling, raising the possibility that nonselective β-blockers could inhibit engraftment after hematopoietic cell transplants (HCT). We observed no effect of β-blockers on steady-state mouse hematopoiesis. However, mice treated with a nonselective β-blocker (carvedilol), but not a β1-selective inhibitor (metoprolol), exhibited impaired hematopoietic regeneration after syngeneic or allogeneic HCTs. At two institutions, patients who received nonselective, but not β1-selective, β-blockers after allogeneic HCT exhibited delayed platelet engraftment and reduced survival. This was particularly observed in patients who received posttransplant chemotherapy for graft-versus-host disease prophylaxis, which also accentuated the inhibitory effect of carvedilol on engraftment in mice. In patients who received autologous HCTs, nonselective β-blockers were associated with little or no delay in engraftment. The inhibitory effect of nonselective β-blockers after allogeneic HCT was overcome by transplanting larger doses of hematopoietic cells. Significance: Patients who receive allogeneic HCTs followed by posttransplant chemotherapy for graft-versus-host disease prophylaxis may be at risk of delayed engraftment and increased mortality if administered nonselective β-blockers after transplantation. Transient discontinuation of nonselective β-blockers or transitioning to β1-selective inhibitors after HCT may accelerate engraftment and improve clinical outcomes. See related commentary by Bhatia, p. 666.","journal":"Cancer Discovery","year":2024,"id":449833,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9512,"is_data_producer":false,"deposit_databanks":null,"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":345888,"name":"Wenhuo Hu","orcid":"0000-0002-8686-7160","position":1,"is_corresponding":false},{"id":411630,"name":"Ashwin Kishtagari","orcid":"0000-0003-1149-4571","position":2,"is_corresponding":false},{"id":288253,"name":"Bo Shen","orcid":"0000-0002-5237-6144","position":3,"is_corresponding":false},{"id":1267540,"name":"Xiang Gao","orcid":"0009-0007-4854-7899","position":4,"is_corresponding":false},{"id":1269639,"name":"Caroline M. Blackman","orcid":"0009-0003-2555-3277","position":5,"is_corresponding":false},{"id":353141,"name":"Adetola A. Kassim","orcid":"0000-0002-0484-5903","position":6,"is_corresponding":false},{"id":1269640,"name":"Naimisha Marneni","orcid":"0009-0008-6237-9024","position":7,"is_corresponding":false},{"id":1269641,"name":"Abhisar V. Cherukuri","orcid":"0009-0002-9849-9307","position":8,"is_corresponding":false},{"id":1269642,"name":"Russell Vittrup","orcid":"0009-0005-0837-719X","position":9,"is_corresponding":false},{"id":906217,"name":"Fatma N. Kalkan","orcid":"0000-0002-1053-1193","position":10,"is_corresponding":false},{"id":351907,"name":"Rahul Shah","orcid":"0000-0001-6187-4690","position":11,"is_corresponding":false},{"id":329848,"name":"Chul Ahn","orcid":"0000-0002-2997-9203","position":12,"is_corresponding":false},{"id":312121,"name":"Ang Gao","orcid":"0000-0001-6530-8768","position":13,"is_corresponding":false},{"id":1269643,"name":"Abeer Ahmedrabie","orcid":"0009-0004-7373-5806","position":14,"is_corresponding":false},{"id":839753,"name":"Robert H. Collins","orcid":"0000-0003-0313-2394","position":15,"is_corresponding":false},{"id":280996,"name":"Amer M. Zeidan","orcid":"0000-0001-7017-8160","position":16,"is_corresponding":false},{"id":861846,"name":"Aram Bidikian","orcid":"0000-0001-5856-5926","position":17,"is_corresponding":false},{"id":619547,"name":"Lohith Gowda","orcid":null,"position":18,"is_corresponding":false},{"id":352732,"name":"Brian C. Shaffer","orcid":"0000-0003-3433-9179","position":19,"is_corresponding":false},{"id":906216,"name":"Yazan F. Madanat","orcid":"0000-0001-9573-2690","position":20,"is_corresponding":false},{"id":563115,"name":"Zhiyu Zhao","orcid":"0000-0001-6308-6997","position":21,"is_corresponding":false},{"id":399105,"name":"Stephen S. Chung","orcid":"0000-0002-1433-7419","position":22,"is_corresponding":false},{"id":55807,"name":"Sean J. Morrison","orcid":"0000-0003-1587-8329","position":23,"is_corresponding":false},{"id":1269638,"name":"Jinsuke Nishino","orcid":"0009-0007-9736-8678","position":0,"is_corresponding":true}],"reference_count":54,"raw_metadata":null,"created_at":"2026-07-19T02:02:20.585759Z","pmid":"39786370","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":[]}