{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T12:17:20Z","timestamp":1790079440981,"version":"4.0.1"},"reference-count":9,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T00:00:00Z","timestamp":1789862400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Hematol. Rep.","Hematology Reports"],"abstract":"<jats:p>Background\/Objectives: In myelodysplastic neoplasms, autoinflammatory syndromes result from dysregulated innate immunity and cause severe, organ-dominant inflammation. Interleukin-1 signaling through the NLRP3 inflammasome is implicated in the pathogenesis of myelodysplastic disease and related inflammatory complications, especially in the context of RAS-pathway activation. Reports describing therapy-related myelodysplastic syndrome with pulmonary autoinflammatory syndromes are rare, and the efficacy of interleukin-1 blockade in this setting has not been previously documented. Results: A man in his 60s with therapy-related myelodysplastic syndrome (del 5q) following rectal chemoradiation developed a recurrent, lung-predominant autoinflammatory syndrome refractory to corticosteroids and Janus kinase inhibition. Next-generation sequencing identified gain-of-function mutations in NRAS, PTPN11, SF3B1, and ASXL1. On two separate occasions, anakinra produced rapid clinical improvement with normalization of inflammatory biomarkers and radiographic resolution; on both occasions, discontinuation of anakinra led to prompt relapse within days, with ferritin rising to above 5500 ng\/mL and C-reactive protein exceeding 300 mg\/L. Conclusions: This case demonstrates that interleukin-1-mediated inflammation can drive pulmonary complications in therapy-related myelodysplastic syndrome. Targeted cytokine blockade with anakinra produced reproducible and measurable clinical improvement when conventional therapies were insufficient. The recurrence of symptoms following anakinra withdrawal, and rapid improvement upon re-administration, underscores the functional link between interleukin-1-driven inflammation and clinical outcomes. The RAS\/MAPK mutational context and the observed on\u2013off response to anakinra further support an interleukin-1-driven mechanism that merits further investigation.<\/jats:p>","DOI":"10.3390\/hematolrep18050068","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T11:09:35Z","timestamp":1790075375000},"page":"68","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Lung-Predominant Hyperinflammatory Syndrome in Therapy-Related Myelodysplastic Syndrome Responsive to Interleukin-1 Blockade"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3632-6945","authenticated-orcid":false,"given":"Quinn","family":"Smith","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, University of Cincinnati Medical Center, Cincinnati, OH 45219, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Arar-Cauley","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Cincinnati Medical Center, Cincinnati, OH 45219, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1182\/blood.2023023723","article-title":"Molecular and clinical presentation of UBA1-mutated myelodysplastic syndromes","volume":"144","author":"Sirenko","year":"2024","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"329","DOI":"10.3390\/hemato2020019","article-title":"Inflammatory and immune disorders associated with myelodysplastic syndromes","volume":"2","author":"Jachiet","year":"2021","journal-title":"Hemato"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e325","DOI":"10.1016\/S2665-9913(20)30127-2","article-title":"Interleukin-1 blockade with high-dose anakinra in patients with COVID-19, acute respiratory distress syndrome, and hyperinflammation: A retrospective cohort study","volume":"2","author":"Cavalli","year":"2020","journal-title":"Lancet Rheumatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"301","DOI":"10.5144\/0256-4947.2013.301","article-title":"Acute fibrinous and organizing pneumonia","volume":"33","author":"Dawamneh","year":"2013","journal-title":"Ann. Saudi Med."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Jiang, D., Chen, X., Li, J., Zhao, L., and Dai, H. (2023). Case report: Corticosteroid-resistant acute fibrinous and organizing pneumonia with myelodysplastic syndrome. Front. Med., 9.","DOI":"10.3389\/fmed.2022.1047783"},{"key":"ref_6","first-page":"101329","article-title":"NLRP3 inflammasome activation and symptom burden in KRAS-mutated CMML patients is reverted by IL-1 blocking therapy","volume":"5","author":"Zamora","year":"2023","journal-title":"Cell Rep. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1182\/blood-2018-10-844654","article-title":"The central role of inflammatory signaling in the pathogenesis of myelodysplastic syndromes","volume":"133","author":"Sallman","year":"2019","journal-title":"Blood"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.leukres.2016.02.005","article-title":"Efficacy of azacitidine in autoimmune and inflammatory disorders associated with myelodysplastic syndromes and chronic myelomonocytic leukemia","volume":"43","author":"Fraison","year":"2016","journal-title":"Leuk. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2739","DOI":"10.1038\/s41375-022-01698-8","article-title":"A phase II prospective trial of azacitidine in steroid-dependent or refractory systemic autoimmune\/inflammatory disorders and VEXAS syndrome associated with MDS and CMML","volume":"36","author":"Mekinian","year":"2022","journal-title":"Leukemia"}],"container-title":["Hematology Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2038-8330\/18\/5\/68\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T11:57:53Z","timestamp":1790078273000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2038-8330\/18\/5\/68"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,20]]},"references-count":9,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,10]]}},"alternative-id":["hematolrep18050068"],"URL":"https:\/\/doi.org\/10.3390\/hematolrep18050068","relation":{},"ISSN":["2038-8330"],"issn-type":[{"value":"2038-8330","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,20]]}}}