{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T18:04:06Z","timestamp":1790100246374,"version":"4.0.1"},"reference-count":22,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007132","name":"Otsuka Pharmaceutical","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007132","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>Acute myeloid leukemia (AML) primarily affects older adults, many of whom are unsuitable for intensive chemotherapy. Hypomethylating agents (HMA) -intravenous (IV) decitabine and subcutaneous (SC) azacitidine- are standard therapeutic options but require frequent hospital visits and substantial healthcare resource use. Oral decitabine\/cedazuridine (DEC-C) offers a therapeutically equivalent alternative that may reduce hospital resource burden and improve patient convenience. This study estimated and compared the economic and organizational impact of IV, SC, and oral HMA administration in AML patients unfit for standard intensive chemotherapy, from the perspective of the Spanish National Health System. A micro\u2011costing model quantified direct non\u2011pharmacological costs associated solely with the administration route across five domains: drug preparation and administration, treatment\u2011related hospitalizations, medical transportation, catheter management, and infections. Resource use was derived from a survey of 30 healthcare professionals across 16 hospitals and valued using official tariffs. Costs were calculated separately for induction and subsequent cycles; drug acquisition costs were excluded. Non\u2011pharmacological costs per patient were \u20ac9,998 for IV decitabine, \u20ac12,177 for SC azacitidine, and \u20ac1,306 for oral DEC\u2011C, representing cost reductions of 87% and 89% for oral therapy versus IV and SC, respectively. Savings were driven mainly by reductions in hospitalization (58\u201361%), transport (13\u201322%), infections (9%\u201312%), administration\u2011related activities (11\u201312%) and the avoidance of catheter-related costs. Oral therapy also markedly reduced resource utilization, including 40\u201350 fewer hours of healthcare professional time, 8\u20139 fewer inpatient days, and 4\u20138 fewer ambulance transfers per patient. Catheter use decreased by 33%, and infection risk declined by 87% versus IV and 54% versus SC. Oral administration substantially reduces direct non\u2011drug costs and frees hospital capacity, offering meaningful organizational efficiencies and contributing to the sustainability of AML care within a resource\u2011constrained health system. These findings reinforce the value of integrating oral HMAs into clinical pathways.<\/jats:p>","DOI":"10.1371\/journal.pone.0358426","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T17:22:16Z","timestamp":1790097736000},"page":"e0358426","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Economic and organizational impact of oral versus intravenous and subcutaneous administration of hypomethylating agents in patients with acute myeloid leukemia not eligible for intensive chemotherapy in Spain"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-1259-1426","authenticated-orcid":true,"given":"Mar\u00eda","family":"Lloret Avell\u00e1","sequence":"first","affiliation":[{"name":"IQVIA","place":["Barcelona, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mafalda","family":"Carmo","sequence":"additional","affiliation":[{"name":"IQVIA","place":["Barcelona, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N\u00faria","family":"Paladio Duran","sequence":"additional","affiliation":[{"name":"Otsuka","place":["Barcelona, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pere","family":"Blancher Parcerisa","sequence":"additional","affiliation":[{"name":"Otsuka","place":["Barcelona, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,9,22]]},"reference":[{"key":"pone.0358426.ref001","article-title":"Acute myeloid leukemia","volume-title":"StatPearls","author":"A Vakiti","year":"2024"},{"issue":"18","key":"pone.0358426.ref002","doi-asserted-by":"crossref","first-page":"4179","DOI":"10.1182\/blood-2008-07-172007","article-title":"Age and acute myeloid leukemia: Real world data on decision to treat and outcomes from the Swedish Acute Leukemia Registry","volume":"113","author":"G Juliusson","year":"2009","journal-title":"Blood"},{"key":"pone.0358426.ref003","doi-asserted-by":"crossref","first-page":"1642472","DOI":"10.3389\/fonc.2025.1642472","article-title":"Unmet needs in patients with acute myeloid leukemia ineligible for intensive approaches: Perspectives from a European expert panel","volume":"15","author":"F Ferrara","year":"2025","journal-title":"Front Oncol"},{"issue":"12","key":"pone.0358426.ref004","doi-asserted-by":"crossref","first-page":"1667","DOI":"10.3390\/jpm13121667","article-title":"Survival outcomes and health-related quality of life in older adults diagnosed with acute myeloid leukemia receiving frontline therapy in daily practice","volume":"13","author":"F Ramos","year":"2023","journal-title":"J Pers Med"},{"issue":"10","key":"pone.0358426.ref005","doi-asserted-by":"crossref","first-page":"3860","DOI":"10.1007\/s12094-025-03875-4","article-title":"Hospital at home for oncologic patients: SEOM\u2013SEHAD consensus on clinical practice","volume":"27","author":"EB Villegas Bruguera","year":"2025","journal-title":"Clin Transl Oncol"},{"key":"pone.0358426.ref006","unstructured":"Sociedad Espa\u00f1ola de Oncolog\u00eda M, Red Espa\u00f1ola de Registros de C. 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