{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:37:59Z","timestamp":1760060279399,"version":"build-2065373602"},"reference-count":31,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T00:00:00Z","timestamp":1755648000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation","award":["824B2004","2023ZD0501300","82341211","U22A20291","82270218","2023-I2M-2-007","2022-I2M-1-022"],"award-info":[{"award-number":["824B2004","2023ZD0501300","82341211","U22A20291","82270218","2023-I2M-2-007","2022-I2M-1-022"]}]},{"name":"Noncommunicable Chronic Diseases\u2014National Science and Technology Major Project","award":["824B2004","2023ZD0501300","82341211","U22A20291","82270218","2023-I2M-2-007","2022-I2M-1-022"],"award-info":[{"award-number":["824B2004","2023ZD0501300","82341211","U22A20291","82270218","2023-I2M-2-007","2022-I2M-1-022"]}]},{"name":"National Natural Science Foundation of China","award":["824B2004","2023ZD0501300","82341211","U22A20291","82270218","2023-I2M-2-007","2022-I2M-1-022"],"award-info":[{"award-number":["824B2004","2023ZD0501300","82341211","U22A20291","82270218","2023-I2M-2-007","2022-I2M-1-022"]}]},{"name":"Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences","award":["824B2004","2023ZD0501300","82341211","U22A20291","82270218","2023-I2M-2-007","2022-I2M-1-022"],"award-info":[{"award-number":["824B2004","2023ZD0501300","82341211","U22A20291","82270218","2023-I2M-2-007","2022-I2M-1-022"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: High-risk chromosomal abnormalities (HRCAs) detected by fluorescence in situ hybridization (FISH) have a well-established adverse prognostic impact in multiple myeloma (MM). It is increasingly recognized that the coexistence of two or more HRCAs identifies a particularly poor-risk subgroup, often referred to as double- or multiple-hit MM. However, there is currently no consensus on its definition. Methods: We retrospectively analyzed a multicenter cohort of 1122 newly diagnosed MM patients from 2008 to 2019. Double-hit MM was defined as the coexistence of at least two of the following four HRCAs: t(14;16), gain(1q), del(17p), and del(1p). Based on this definition, we constructed a novel prognostic model, the HBDH (Institute of Hematology &amp; Blood Diseases Hospital) double-hit model, and assessed its prognostic value for progression-free survival (PFS) and overall survival (OS). Results: According to the HBDH model, double-hit patients showed significantly inferior outcomes compared to non-double-hit patients, with median PFS of 20.6 vs. 53.3 months (p &lt; 0.001) and median OS of 40.2 vs. 84.2 months (p &lt; 0.001). The addition of del(13q), t(4;14), or t(11;14) did not improve the prognostic performance of the model. Importantly, the HBDH model was independent of the International Staging System (ISS), elevated LDH, and advanced age. Conclusions: The HBDH double-hit model identifies a subset of ultra-high-risk MM patients carrying at least two major HRCAs, providing a simple and robust framework for prognostic stratification and a potential reference for future biologically driven treatment approaches.<\/jats:p>","DOI":"10.3390\/cancers17162703","type":"journal-article","created":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T07:50:46Z","timestamp":1755676246000},"page":"2703","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Development of a Cytogenetic Double-Hit Model for Survival Prediction in Multiple Myeloma"],"prefix":"10.3390","volume":"17","author":[{"given":"Chenxing","family":"Du","sequence":"first","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China"},{"name":"Tianjin Institutes of Health Science, Tianjin 301600, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3885-6782","authenticated-orcid":false,"given":"Jian","family":"Cui","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China"},{"name":"Tianjin Institutes of Health Science, Tianjin 301600, China"},{"name":"LeBow Institute for Myeloma Therapeutics and Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingyu","family":"Xu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China"},{"name":"Tianjin Institutes of Health Science, Tianjin 301600, China"},{"name":"LeBow Institute for Myeloma Therapeutics and Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenqiang","family":"Yan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese 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& Peking Union Medical College, Tianjin 300020, China"},{"name":"Tianjin Institutes of Health Science, Tianjin 301600, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuhui","family":"Deng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China"},{"name":"Tianjin Institutes of Health Science, Tianjin 301600, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuhua","family":"Yi","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China"},{"name":"Tianjin Institutes of Health Science, Tianjin 301600, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6167-3319","authenticated-orcid":false,"given":"Yan","family":"Xu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China"},{"name":"Tianjin Institutes of Health Science, Tianjin 301600, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chengwen","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China"},{"name":"Tianjin Institutes of Health Science, Tianjin 301600, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiawei","family":"Zhao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China"},{"name":"Tianjin Institutes of Health Science, Tianjin 301600, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dehui","family":"Zou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China"},{"name":"Tianjin Institutes of Health Science, Tianjin 301600, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8752-0644","authenticated-orcid":false,"given":"Lugui","family":"Qiu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China"},{"name":"Tianjin Institutes of Health Science, Tianjin 301600, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gang","family":"An","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & 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