{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T02:35:50Z","timestamp":1764729350900,"version":"3.46.0"},"reference-count":21,"publisher":"Springer Science and Business Media LLC","issue":"11","license":[{"start":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T00:00:00Z","timestamp":1760054400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T00:00:00Z","timestamp":1760054400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Universit\u00e0 degli Studi di Bari Aldo Moro"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Ann Hematol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Autologous stem cell transplantation (ASCT), doubled in selected cases, followed by lenalidomide maintenance (LM) remains the standard treatment after induction therapy for newly diagnosed, transplant eligible patients with multiple myeloma (TEMM). Notwithstanding, evidences about how these approaches have been applied and how they have performed in the real-life setting, before the introduction of daratumumab within the induction regimens, are quite limited. Herein, we report the outcome of 300 MM patients, who underwent single (45%) or double (55%) ASCT, and received (42%) or not (58%) lenalidomide maintenance, outside of clinical trials, between December 2001 and February 2020, within the \u201cRete Ematologica Pugliese\u201d. After a median follow-up of 65 months (range: 9-186), median PFS was significantly longer in patients who underwent double ASCT compared to those who received single ASCT (66 vs. 53 months, respectively,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.01). Likewise, after a median follow-up of 62 months (range: 9-174), patients who received LM had a significantly better PFS respect to those who did not (72 vs. 36 months, respectively\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001). Concerning OS, it was not influenced by single or double ASCT (although a trend favoring double ASCT was observed), while LM significantly improved OS (142 vs. 108 months,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.01). At multivariable analysis factors influencing PFS were achievement of complete remission after first ASCT, double ASCT and LM, while those impacting on OS were high risk cytogenetics, LDH and LM. In the context of a rapidly changing therapeutic scenario, our data might contribute to a real-life, historical benchmark for current and future treatments of TEMM patients.\n                  <\/jats:p>","DOI":"10.1007\/s00277-025-06627-0","type":"journal-article","created":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T08:16:27Z","timestamp":1760084187000},"page":"6097-6104","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Single versus double autologous stem cell transplantation and lenalidomide maintenance versus no maintenance therapy in newly-diagnosed patients with multiple myeloma: a real-life, vintage snapshot after twenty-three years from the Rete Ematologica Pugliese"],"prefix":"10.1007","volume":"104","author":[{"given":"Nicola","family":"Di 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Nat Rev Clin Oncol 7. https:\/\/doi.org\/10.1038\/s41571-025-01041-xOnline ahead of print.PMID: 40624367","DOI":"10.1038\/s41571-025-01041-x"},{"issue":"3","key":"6627_CR2","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1038\/s41409-024-02490-1","volume":"60","author":"N Grieb","year":"2025","unstructured":"Grieb N, Oeser A, Ferle M, Hanke F, Flossdorf S, Sauer S, Goldschmidt H, M\u00fcller-Tidow C, Salwender HJ, Fenk R, Engelhardt M, Zeiser R, Vucinic V, Franke GN, Blau IW, Teschner D, Einsele H, Kimmich C, Kull M, Besemer B, Gagelmann N, Kr\u00f6ger N, Neumuth T, Platzbecker U, Merz M (2025) German registry for hematopoietic stem cell transplantation and cell therapy (DRST). Single versus tandem autologous stem cell transplantation in newly diagnosed multiple myeloma. Bone Marrow Transpl 60(3):335\u2013345. https:\/\/doi.org\/10.1038\/s41409-024-02490-1Epub 2024 Dec 5. PMID: 39638882; PMCID: PMC11893441","journal-title":"Bone Marrow Transpl"},{"key":"6627_CR3","doi-asserted-by":"publisher","unstructured":"Baril\u00e0 G, Grassi A, Conticello C, Mina R, Marcon C, Fazio F, Cartia CS, Tinelli M, Del Giudice ML, Pilerci S, Belotti A, Pascarella A, Tafuri M, Rocchi S, Mancuso K, Sgherza N, Mele G, Scomazzon E, Gentile M, Porrazzo M, Pescosta N, Furlan A, Febbo MA, Clissa C, Casson A, Ribolla R, Maroccia A, Lisi C, Martino EA, Annibali O, Buda G, Antonioli E, Mangiacavalli S, Tosetto A, Musto P, Gay F, Zamagni E, Petrucci MT, Di Raimondo F, Patriarca F, Zambello R (2025)Lenalidomide maintenance after bortezomib, thalidomide and dexamethasone (VTD) induction and autologous stem cell transplantation: an Italian real-life study of 602 patients. haematol.\u00a0https:\/\/doi.org\/10.3324\/haematol.2024.286825. Online ahead of print. PMID: 40304063.","DOI":"10.3324\/haematol.2024.286825"},{"issue":"26","key":"6627_CR4","doi-asserted-by":"publisher","first-page":"2495","DOI":"10.1056\/NEJMoa032290","volume":"349","author":"M Attal","year":"2003","unstructured":"Attal M, Harousseau JL, Facon T, Guilhot F, Doyen C, Fuzibet JG, Monconduit M, Hulin C, Caillot D, Bouabdallah R, Voillat L, Sotto JJ, Grosbois B, Bataille R, InterGroupe Francophone du My\u00e9lome (2003) Single versus double autologous stem-cell transplantation for multiple myeloma. N Engl J Med 349(26):2495\u20132502. https:\/\/doi.org\/10.1056\/NEJMoa032290. Erratum in: N Engl J Med. 2004;350(25):2628. PMID: 14695409","journal-title":"N Engl J Med"},{"issue":"17","key":"6627_CR5","doi-asserted-by":"publisher","first-page":"2434","DOI":"10.1200\/JCO.2006.10.2509","volume":"25","author":"M Cavo","year":"2007","unstructured":"Cavo M, Tosi P, Zamagni E, Cellini C, Tacchetti P, Patriarca F, Di Raimondo F, Volpe E, Ronconi S, Cangini D, Narni F, Carubelli A, Masini L, Catalano L, Fiacchini M, de Vivo A, Gozzetti A, Lazzaro A, Tura S, Baccarani M (2007) Prospective, randomized study of single compared with double autologous stem-cell transplantation for multiple myeloma: Bologna 96 clinical study. J Clin Oncol 25(17):2434\u20132441. https:\/\/doi.org\/10.1200\/JCO.2006.10.2509","journal-title":"J Clin Oncol"},{"issue":"6","key":"6627_CR6","doi-asserted-by":"publisher","first-page":"e456","DOI":"10.1016\/S2352-3026(20)30099-5","volume":"7","author":"M Cavo","year":"2020","unstructured":"Cavo M, Gay F, Beksac M, Pantani L, Petrucci MT, Dimopoulos MA, Dozza L, van der Holt B, Zweegman S, Oliva S, van der Velden VHJ, Zamagni E, Palumbo GA, Patriarca F, Montefusco V, Galli M, Maisnar V, Gamberi B, Hansson M, Belotti A, Pour L, Ypma P, Grasso M, Croockewit A, Ballanti S, Offidani M, Vincelli ID, Zambello R, Liberati AM, Andersen NF, Broijl A, Troia R, Pascarella A, Benevolo G, Levin MD, Bos G, Ludwig H, Aquino S, Morelli AM, Wu KL, Boersma R, Hajek R, Durian M, von dem Borne PA, di Toritto T, Zander T, Driessen C, Specchia G, Waage A, Gimsing P, Mellqvist UH, van Marwijk Kooy M, Minnema M, Mandigers C, Cafro AM, Palmas A, Carvalho S, Spencer A, Boccadoro M, Sonneveld P (2020) Autologous haematopoietic stem-cell transplantation versus bortezomib-melphalan-prednisone, with or without bortezomib-lenalidomide-dexamethasone consolidation therapy, and lenalidomide maintenance for newly diagnosed multiple myeloma (EMN02\/HO95): a multicentre, randomised, open-label, phase 3 study. Lancet Haematol 7(6):e456\u2013e468. https:\/\/doi.org\/10.1016\/S2352-3026(20)30099-5. (Epub 2020 Apr 30. PMID: 32359506)","journal-title":"Lancet Haematol"},{"key":"6627_CR7","doi-asserted-by":"publisher","unstructured":"Tacchetti P, Pantani L, Patriarca F, Petrucci MT, Zamagni E, Dozza L, Galli M, Di Raimondo F, Crippa C, Boccadoro M, Barbato S, Tosi P, Narni F, Montefusco V, Testoni N, Spadano A, Terragna C, Pescosta N, Marzocchi G, Cellini C, Galieni P, Ronconi S, Gobbi M, Catalano L, Lazzaro A, De Sabbata G, Cangialosi C, Ciambelli F, Musto P, Elice F, Cavo M (2020) GIMEMA (Gruppo Italiano Malattie Ematologiche dell\u2019Adulto Italian Myeloma Network). Bortezomib, thalidomide, and dexamethasone followed by double autologous haematopoietic stem-cell transplantation for newly diagnosed multiple myeloma (GIMEMA-MMY-3006): long-term follow-up analysis of a randomised phase 3, open-label study. Lancet Haematol. 7(12):e861-e873. https:\/\/doi.org\/10.1016\/S2352-3026(20)30323-9. 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Blood 132(Supplement 1):124. https:\/\/doi.org\/10.1182\/blood-2018-99-112899","journal-title":"Blood"},{"issue":"11","key":"6627_CR9","doi-asserted-by":"publisher","first-page":"2134","DOI":"10.1016\/j.bbmt.2019.07.004","volume":"25","author":"N Gagelmann","year":"2019","unstructured":"Gagelmann N, Eikema DJ, Koster L, Caillot D, Pioltelli P, Lleonart JB, Rem\u00e9nyi P, Blaise D, Schaap N, Trneny M, Passweg J, Porras RP, Cahn JY, Musso M, Poir\u00e9 X, Fenk R, It\u00e4l\u00e4-Remes M, Pavone V, Fouillard L, Maertens J, Bron D, Pouli A, Schroyens W, Sch\u00f6nland S, Garderet L, Yakoub-Agha I, Kr\u00f6ger N (2019) Tandem autologous stem cell transplantation improves outcomes in newly diagnosed multiple myeloma with extramedullary disease and High-Risk cytogenetics: A study from the chronic malignancies working party of the European society for blood and marrow transplantation. Biol Blood Marrow Transpl 25(11):2134\u20132142. https:\/\/doi.org\/10.1016\/j.bbmt.2019.07.004Epub 2019 Jul 6. PMID: 31288095","journal-title":"Biol Blood Marrow Transpl"},{"issue":"20","key":"6627_CR10","doi-asserted-by":"publisher","first-page":"2029","DOI":"10.1182\/blood.2023023597","volume":"143","author":"C Touzeau","year":"2024","unstructured":"Touzeau C, Perrot A, Hulin C, Manier S, Macro M, Chretien ML, Karlin L, Escoffre M, Jacquet C, Tiab M, Leleu X, Avet-Loiseau H, Jobert A, Planche L, Corre J, Moreau P (2024) Daratumumab, carfilzomib, lenalidomide, and dexamethasone with tandem transplant for high-risk newly diagnosed myeloma. Blood 143(20):2029\u20132036. https:\/\/doi.org\/10.1182\/blood.2023023597","journal-title":"Blood"},{"issue":"1","key":"6627_CR11","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1200\/JCO.23.01696","volume":"42","author":"LB Leypoldt","year":"2024","unstructured":"Leypoldt LB, Tichy D, Besemer B, H\u00e4nel M, Raab MS, Mann C, Munder M, Reinhardt HC, Nogai A, G\u00f6rner M, Ko YD, de Wit M, Salwender H, Scheid C, Graeven U, Peceny R, Staib P, Dieing A, Einsele H, Jauch A, Hundemer M, Zago M, Po\u017eek E, Benner A, Bokemeyer C, Goldschmidt H, Weisel KC (2024) Isatuximab, carfilzomib, lenalidomide, and dexamethasone for the treatment of High-Risk newly diagnosed multiple myeloma. J Clin Oncol 42(1):26\u201337 Epub 2023 Sep 27. 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Blood Cancer J 14(1):69. https:\/\/doi.org\/10.1038\/s41408-024-01030-w.PMID","journal-title":"Blood Cancer J"},{"issue":"5","key":"6627_CR13","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1111\/bjh.13994","volume":"173","author":"EK Mai","year":"2016","unstructured":"Mai EK, Benner A, Bertsch U, Brossart P, H\u00e4nel A, Kunzmann V, Naumann R, Neben K, Egerer G, Ho AD, Hillengass J, Raab MS, Neubauer A, Peyn A, Ko YD, Peter N, Scheid C, Goldschmidt H (2016) Single versus tandem high-dose Melphalan followed by autologous blood stem cell transplantation in multiple myeloma: long-term results from the phase III GMMG-HD2 trial. Br J Haematol 173(5):731\u2013741. https:\/\/doi.org\/10.1111\/bjh.13994Epub 2016 Mar 17. 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N Engl J Med. https:\/\/doi.org\/10.1056\/NEJMoa2505133","journal-title":"N Engl J Med"},{"issue":"2","key":"6627_CR16","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1056\/NEJMoa2204925","volume":"387","author":"PG Richardson","year":"2022","unstructured":"Richardson PG, Jacobus SJ, Weller EA, Hassoun H, Lonial S, Raje NS, Medvedova E, McCarthy PL, Libby EN, Voorhees PM, Orlowski RZ, Anderson LD Jr, Zonder JA, Milner CP, Gasparetto C, Agha ME, Khan AM, Hurd DD, Gowin K, Kamble RT, Jagannath S, Nathwani N, Alsina M, Cornell RF, Hashmi H, Campagnaro EL, Andreescu AC, Gentile T, Liedtke M, Godby KN, Cohen AD, Openshaw TH, Pasquini MC, Giralt SA, Kaufman JL, Yee AJ, Scott E, Torka P, Foley A, Fulciniti M, Hebert K, Samur MK, Masone K, Maglio ME, Zeytoonjian AA, Nadeem O, Schlossman RL, Laubach JP, Paba-Prada C, Ghobrial IM, Perrot A, Moreau P, Avet-Loiseau H, Attal M, Anderson KC, Munshi NC (2022) DETERMINATION investigators. Triplet therapy, transplantation, and maintenance until progression in myeloma. N Engl J Med 387(2):132\u2013147. https:\/\/doi.org\/10.1056\/NEJMoa2204925Epub 2022 Jun 5. PMID: 35660812; PMCID: PMC10040899","journal-title":"N Engl J Med"},{"issue":"29","key":"6627_CR17","doi-asserted-by":"publisher","first-page":"3279","DOI":"10.1200\/JCO.2017.72.6679","volume":"35","author":"PL McCarthy","year":"2017","unstructured":"McCarthy PL, Holstein SA, Petrucci MT, Richardson PG, Hulin C, Tosi P, Bringhen S, Musto P, Anderson KC, Caillot D, Gay F, Moreau P, Marit G, Jung SH, Yu Z, Winograd B, Knight RD, Palumbo A, Attal M (2017) Lenalidomide maintenance after autologous Stem-Cell transplantation in newly diagnosed multiple myeloma: A Meta-Analysis. J Clin Oncol 35(29):3279\u20133289 Epub 2017 Jul 25. PMID: 28742454; PMCID: PMC5652871","journal-title":"J Clin Oncol"},{"issue":"4","key":"6627_CR18","doi-asserted-by":"publisher","first-page":"1159","DOI":"10.1111\/bjh.19353","volume":"204","author":"A Hwang","year":"2024","unstructured":"Hwang A, Hayden P, Pawlyn C, McLornan D, Garderet L (2024) The role of maintenance therapy following autologous stem cell transplantation in newly diagnosed multiple myeloma: considerations on behalf of the chronic malignancies working party of the EBMT. Br J Haematol 204(4):1159\u20131175. https:\/\/doi.org\/10.1111\/bjh.19353","journal-title":"Br J Haematol"},{"issue":"Supplement 1","key":"6627_CR19","doi-asserted-by":"publisher","first-page":"1371","DOI":"10.1182\/blood-2022-165376","volume":"140","author":"C Pawlyn","year":"2022","unstructured":"Pawlyn C, Menzies T, Davies FE, de Tute RM, Henderson R, Cook G, Jenner MW, Jones JR, Kaiser MF, Drayson MT, Owen RG, Cairns D, Morgan JG, Jackson G (2022) Defining the optimal duration of Lenalidomide maintenance after autologous stem cell transplant - data from the myeloma XI trial. 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Expert Rev Hematol 18:1\u201316. https:\/\/doi.org\/10.1080\/17474086.2025.2525457","journal-title":"Expert Rev Hematol"}],"container-title":["Annals of Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00277-025-06627-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00277-025-06627-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00277-025-06627-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T02:31:42Z","timestamp":1764729102000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00277-025-06627-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,10]]},"references-count":21,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["6627"],"URL":"https:\/\/doi.org\/10.1007\/s00277-025-06627-0","relation":{},"ISSN":["1432-0584"],"issn-type":[{"type":"electronic","value":"1432-0584"}],"subject":[],"published":{"date-parts":[[2025,10,10]]},"assertion":[{"value":"19 July 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 September 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 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":"This study was conducted in accordance with the Declaration of Helsinki and approved by the local ethics committee (Comitato Etico ASL Lecce, 73100, Italy; date of approval: 13 February 2023). Informed consent was obtained from all the subjects involved in this study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}