{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T00:22:59Z","timestamp":1760746979633,"version":"build-2065373602"},"reference-count":14,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T00:00:00Z","timestamp":1760659200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T00:00:00Z","timestamp":1760659200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001734","name":"Copenhagen University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001734","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Orphanet J Rare Dis"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Sickle cell anemia (SCA) and multiple myeloma (MM) are debilitating hematologic diseases impacting hemoglobin and plasma cells, respectively. Despite differing origins, they share overlapping clinical features including bone pain and anemia. A cornerstone of SCA is to induce fetal hemoglobin through hydroxyurea treatment. Lenalidomide, a central treatment of MM, has also been shown to induce fetal hemoglobin in vitro. Here we present a case of a young woman with SCA and subsequently multiple myeloma. When lenalidomide was used as part of multiple myeloma treatment, we investigated the proposed induction of fetal hemoglobin, using high-pressure liquid chromatography. Over a treatment period of 114 days, we did not observe lenalidomide-induced increases in fetal hemoglobin and were thereby unable to replicate in vitro findings. Moreover, the case highlights many difficulties of diagnosing and treating patients with SCA and concurrent malignancies.<\/jats:p>","DOI":"10.1186\/s13023-025-04052-0","type":"journal-article","created":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T13:20:47Z","timestamp":1760707247000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Unexpected absence of fetal hemoglobin induction by lenalidomide in a patient with sickle cell anemia with concurrent multiple myeloma"],"prefix":"10.1186","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-0254-6808","authenticated-orcid":false,"given":"Rasmus","family":"R\u00f8nnemoes","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1876-8187","authenticated-orcid":false,"given":"Jens","family":"Helby","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amina","family":"Nardo-Marino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8034-1523","authenticated-orcid":false,"given":"Morten Hanefeld","family":"Dziegiel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6116-5114","authenticated-orcid":false,"given":"Jesper","family":"Petersen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9943-7007","authenticated-orcid":false,"given":"Agoston Gyula","family":"Szabo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nina","family":"Toft","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2082-0738","authenticated-orcid":false,"given":"Andreas","family":"Glenth\u00f8j","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,10,17]]},"reference":[{"issue":"9757","key":"4052_CR1","doi-asserted-by":"publisher","first-page":"2018","DOI":"10.1016\/S0140-6736(10)61029-X","volume":"376","author":"DC Rees","year":"2010","unstructured":"Rees DC, Williams TN, Gladwin MT. Sickle-cell disease. Lancet. 2010;376(9757):2018\u201331.","journal-title":"Lancet"},{"key":"4052_CR2","doi-asserted-by":"crossref","unstructured":"Platt OS, Orkin SH, Dover G, Beardsley GP, Miller B, Nathan DG. Rapid publication hydroxyurea enhances fetal hemoglobin production in sickle cell anemia. J Clin Invest. 1984;74(2):652-6.","DOI":"10.1172\/JCI111464"},{"issue":"1","key":"4052_CR3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/00498254.2021.2018628","volume":"52","author":"C S\u00e4ll","year":"2022","unstructured":"S\u00e4ll C, Fogt Hjorth C. In vitro drug-drug interactions of decitabine and tetrahydrouridine involving drug transporters and drug metabolising enzymes. Xenobiotica. 2022;52(1):1\u201315.","journal-title":"Xenobiotica"},{"issue":"3","key":"4052_CR4","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1056\/NEJMoa2031054","volume":"384","author":"H Frangoul","year":"2021","unstructured":"Frangoul H, Altshuler D, Cappellini MD, Chen YS, Domm J, Eustace BK, et al. CRISPR-Cas9 gene editing for sickle cell disease and \u03b2-Thalassemia. N Engl J Med. 2021;384(3):252\u201360.","journal-title":"N Engl J Med"},{"issue":"1","key":"4052_CR5","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1172\/JCI32322","volume":"118","author":"LA Moutouh-De Parseval","year":"2008","unstructured":"Moutouh-De Parseval LA, Verhelle D, Glezer E, Jensen-Pergakes K, Ferguson GD, Corral LG, et al. Pomalidomide and Lenalidomide regulate erythropoiesis and fetal hemoglobin production in human CD34 + cells. J Clin Invest. 2008;118(1):248\u201358.","journal-title":"J Clin Invest"},{"issue":"4","key":"4052_CR6","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1080\/14653240902849788","volume":"11","author":"CD Fitzhugh","year":"2009","unstructured":"Fitzhugh CD, Hsieh MM, Bolan CD, Saenz C, Tisdale JF. Granulocyte colony-stimulating factor (G-CSF) administration in individuals with sickle cell disease: time for a moratorium? Cytotherapy. 2009;11(4):464\u201371.","journal-title":"Cytotherapy"},{"issue":"2","key":"4052_CR7","first-page":"86","volume":"2","author":"M Nygaard","year":"2013","unstructured":"Nygaard M, Petersen J, Bjerrum OW. Haemoglobinopathia Ypsilanti - A rare, but important differential diagnosis to polycythaemia Vera. Leuk Res Rep. 2013;2(2):86\u20138.","journal-title":"Leuk Res Rep"},{"key":"4052_CR8","volume-title":"Rapid and automated quantitation of dense red blood cells: A robust biomarker of hydroxyurea treatment response","author":"A Sadaf","year":"2021","unstructured":"Sadaf A, Quinn CT, Korpik JB, Pfeiffer A, Reynaud M, Niss O, et al. Rapid and automated quantitation of dense red blood cells: A robust biomarker of hydroxyurea treatment response. Volume 90. Molecules, and Diseases. Academic Press Inc.;: Blood Cells; 2021."},{"issue":"15","key":"4052_CR9","doi-asserted-by":"publisher","first-page":"3136","DOI":"10.1182\/blood-2012-04-424184","volume":"120","author":"P Bartolucci","year":"2012","unstructured":"Bartolucci P, Brugnara C, Teixeira-Pinto A, Pissard S, Moradkhani K, Jouault H, et al. Erythrocyte density in sickle cell syndromes is associated with specific clinical manifestations and hemolysis. Blood. 2012;120(15):3136\u201341.","journal-title":"Blood"},{"issue":"2","key":"4052_CR10","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1172\/JCI200316672","volume":"111","author":"VP Cokic","year":"2003","unstructured":"Cokic VP, Smith RD, Beleslin-Cokic BB, Njoroge JM, Miller JL, Gladwin MT, et al. Hydroxyurea induces fetal hemoglobin by the nitric oxide\u2013dependent activation of soluble Guanylyl cyclase. J Clin Invest. 2003;111(2):231\u20139.","journal-title":"J Clin Invest"},{"issue":"1","key":"4052_CR11","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1016\/0006-291X(68)90266-0","volume":"33","author":"HL Elford","year":"1968","unstructured":"Elford HL. Effect of hydroxyurea on ribonucleotide reductase. Biochem Biophys Res Commun. 1968;33(1):129\u201335.","journal-title":"Biochem Biophys Res Commun"},{"issue":"11","key":"4052_CR12","doi-asserted-by":"publisher","first-page":"1481","DOI":"10.1182\/blood-2015-09-667923","volume":"127","author":"BM Dulmovits","year":"2016","unstructured":"Dulmovits BM, Appiah-Kubi AO, Papoin J, Hale J, He M, Al-Abed Y, et al. Pomalidomide reverses \u03b3-globin Silencing through the transcriptional reprogramming of adult hematopoietic progenitors. Blood. 2016;127(11):1481\u201392.","journal-title":"Blood"},{"issue":"4","key":"4052_CR13","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1038\/jhg.2011.12","volume":"56","author":"P Bhatnagar","year":"2011","unstructured":"Bhatnagar P, Purvis S, Barron-Casella E, DeBaun MR, Casella JF, Arking DE, et al. Genome-wide association study identifies genetic variants influencing F-cell levels in sickle-cell patients. 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Am J Blood Res. 2014;4(1):27\u201332.","journal-title":"Am J Blood Res"}],"container-title":["Orphanet Journal of Rare Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-025-04052-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13023-025-04052-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-025-04052-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T13:20:49Z","timestamp":1760707249000},"score":1,"resource":{"primary":{"URL":"https:\/\/ojrd.biomedcentral.com\/articles\/10.1186\/s13023-025-04052-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,17]]},"references-count":14,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["4052"],"URL":"https:\/\/doi.org\/10.1186\/s13023-025-04052-0","relation":{},"ISSN":["1750-1172"],"issn-type":[{"value":"1750-1172","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,17]]},"assertion":[{"value":"31 January 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 September 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 October 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Written informed consent for participation in this case report was obtained from the patient in accordance with Danish law. A copy of the written consent is available for review by the Editor-in-Chief of this journal.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare the following conflicts of interest: JH: Consultant for Sanofi and Disc Medicine. Received research funding and a conference travel grant from Sanofi. AG: Consultant for Agios Pharmaceuticals, Inc., Bristol Myers Squibb, Novartis Pharmaceuticals, Novo Nordisk A\/S, Pharmacosmos UK Ltd, and Vertex Pharmaceuticals. Received research support from Agios Pharmaceuticals, Inc., Novo Nordisk A\/S, Saniona, and Sanofi. AGS: Consultant for Janssen, Sanofi, Takeda. Research funding from Bristol Myers Squibb, GSK and Takeda. All other authors declare no conflicts of interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"522"}}