{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T13:59:01Z","timestamp":1777384741429,"version":"3.51.4"},"reference-count":24,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,4,26]],"date-time":"2026-04-26T00:00:00Z","timestamp":1777161600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Current Oncology"],"abstract":"<jats:p>Introduction: High-risk multiple myeloma (HRMM) is primarily defined by adverse cytogenetic abnormalities that are associated with inferior outcomes despite contemporary treatment with novel induction agents and autologous stem cell transplantation (ASCT). While the accumulation of high-risk lesions has been proposed to further stratify prognosis, the relative impact of single-hit versus double-hit HRMM on post-transplant outcomes in real-world clinical practice remains incompletely characterized. Methods: We conducted a multicenter retrospective cohort study of transplant-eligible adults with HRMM undergoing upfront ASCT between 2009 and 2024 at three U.S. academic centers. Patients were categorized as single-hit HRMM or double-hit HRMM based on the number of high-risk cytogenetic abnormalities at diagnosis. Response rates, progression-free survival (PFS), and overall survival (OS) were compared between groups using standard statistical methods. Results: A total of 154 patients were included, of whom 63 had SH-HRMM, and 91 had DH-HRMM. Following induction therapy, overall response rates (ORR) were high and comparable between groups. After ASCT, ORR was significantly higher in SH-HRMM compared with DH-HRMM (97% vs. 82%, p = 0.006), although depth of response did not differ significantly. With a median follow-up of 150 months, median OS was 103 months in SH-HRMM and 94 months in DH-HRMM (p = 0.40). Median PFS was 36 months and 31 months, respectively (p = 0.20). Restricted mean survival time analyses similarly demonstrated no significant differences in OS or PFS between groups. Although ORR differed, depth of response and long-term survival did not. Conclusions: In this real-world cohort of transplant-treated HRMM, single-hit disease was associated with a higher likelihood of achieving post-ASCT response; however, no significant differences in long-term survival outcomes were observed between single-hit and double-hit HRMM. These findings suggest that cytogenetic hit burden alone may be insufficient to predict post-transplant survival, highlighting the need for refined risk stratification incorporating additional biological and response-based markers.<\/jats:p>","DOI":"10.3390\/curroncol33050246","type":"journal-article","created":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T08:12:31Z","timestamp":1777363951000},"page":"246","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Outcomes of Double-Hit and Single High-Risk Cytogenetic Newly Diagnosed Myeloma in Transplant-Eligible Patients"],"prefix":"10.3390","volume":"33","author":[{"given":"Raeef","family":"Rahman","sequence":"first","affiliation":[{"name":"School of Medicine, University of Kansas, Kansas City, KS 66160, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7537-0112","authenticated-orcid":false,"given":"Anas","family":"Zayad","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hamad Medical Corporation, Doha P.O. Box 3050, Qatar"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmel","family":"Awadallah","sequence":"additional","affiliation":[{"name":"Division of Internal Medicine, St John Episcopal Hospital, Far Rockaway, NY 11691, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-5209-4848","authenticated-orcid":false,"given":"Beining","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Medicine at Shanghai Medical College, Fudan University, Shanghai 201399, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianzheng","family":"Wu","sequence":"additional","affiliation":[{"name":"Division of Biostatistics and Data Science, University of Kansas Medical Center, Kansas City, KS 66205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aroog","family":"Khaliq","sequence":"additional","affiliation":[{"name":"Division of Hematologic Malignancies & Cellular Therapeutics, University of Kansas Medical Center, Westwood, KS 66205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-7464-6898","authenticated-orcid":false,"given":"Prerna","family":"Mewawalla","sequence":"additional","affiliation":[{"name":"Division of Hematology and Cellular Therapy, Allegheny Health Network Cancer Institute, Pittsburgh, PA 15224, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4547-7534","authenticated-orcid":false,"given":"Shebli","family":"Atrash","sequence":"additional","affiliation":[{"name":"Levine Cancer Center, Atrium Health, Wake Forest University School of Medicine, Charlotte, NC 28204, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9767-1158","authenticated-orcid":false,"given":"Dinesh Pal","family":"Mudaranthakam","sequence":"additional","affiliation":[{"name":"Division of Biostatistics and Data Science, University of Kansas Medical Center, Kansas City, KS 66205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph","family":"McGuirk","sequence":"additional","affiliation":[{"name":"Division of Hematologic Malignancies & Cellular Therapeutics, University of Kansas Medical Center, Westwood, KS 66205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3168-2521","authenticated-orcid":false,"given":"Zahra","family":"Mahmoudjafari","sequence":"additional","affiliation":[{"name":"Division of Hematologic Malignancies & Cellular Therapeutics, University of Kansas Medical Center, Westwood, KS 66205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muhammad Umair","family":"Mushtaq","sequence":"additional","affiliation":[{"name":"Division of Hematologic Malignancies & Cellular Therapeutics, University of Kansas Medical Center, Westwood, KS 66205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6603-185X","authenticated-orcid":false,"given":"Al-Ola","family":"Abdallah","sequence":"additional","affiliation":[{"name":"Division of Hematologic Malignancies & Cellular Therapeutics, University of Kansas Medical Center, Westwood, KS 66205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nausheen","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Division of Hematologic Malignancies & Cellular Therapeutics, University of Kansas Medical Center, Westwood, KS 66205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jordan","family":"Snyder","sequence":"additional","affiliation":[{"name":"Division of Hematologic Malignancies & Cellular Therapeutics, University of Kansas Medical Center, Westwood, KS 66205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7899-7078","authenticated-orcid":false,"given":"Anita","family":"Mazloom","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Mitchell Cancer Institute, University of South Alabama, Mobile, AL 36604, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5299-4233","authenticated-orcid":false,"given":"Omar","family":"Alkharabsheh","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Mitchell Cancer Institute, University of South Alabama, Mobile, AL 36604, USA"},{"name":"Division of Hematology and Oncology, University of Cincinnati, Cincinnati, OH 45267, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mansi R.","family":"Shah","sequence":"additional","affiliation":[{"name":"Division of Hematology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08901, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1802","DOI":"10.1002\/ajh.27422","article-title":"Multiple myeloma: 2024 update on diagnosis, risk-stratification, and management","volume":"99","author":"Rajkumar","year":"2024","journal-title":"Am. 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