{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T03:03:52Z","timestamp":1789182232976,"version":"build-2803163510"},"reference-count":30,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2024,10,1]],"date-time":"2024-10-01T00:00:00Z","timestamp":1727740800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Introduction: The growing body of evidence around sexual and gender dimorphism in medicine, particularly in oncology, has highlighted differences in treatment response, outcomes, and side effects between males and females. Differences in drug metabolism, distribution, and elimination, influenced by factors like body composition and enzyme expression, contribute to these variations. Methods: We retrospectively analyzed data of 112 multiple myeloma (MM) patients treated with first-line high-dose chemotherapy (HDCT) with treosulfan and melphalan (TreoMel) followed by autologous stem cell transplantation (ASCT) at a single academic center between January 2020 and August 2022. We assessed response rate, progression-free survival (PFS), overall survival (OS), and toxicities in relation to gender and treosulfan exposure. Results: Our analysis revealed significant gender-specific differences in treosulfan exposure. Females had higher peak levels (343.8 vs. 309.0 mg\/L, p = 0.0011) and area under the curve (AUC) (869.9 vs. 830.5 mg*h\/L, p = 0.0427) compared to males. Higher treosulfan exposure was associated with increased mortality in females but not in males. Females with treosulfan AUC &gt; 900 mg*h\/L had significantly shorter overall survival, while PFS was unaffected by treosulfan exposure. Conclusion: Our study demonstrates that female patients undergoing TreoMel HDCT have higher treosulfan exposure than males and that females with higher levels are at increased risk for toxicity and adverse outcomes. These data suggest that higher treosulfan doses do not confer a benefit in terms of better outcomes for females. Therefore, exploring lower treosulfan doses for female MM patients undergoing TreoMel HDCT may be warranted to mitigate toxicity and improve outcomes.<\/jats:p>","DOI":"10.3390\/cancers16193364","type":"journal-article","created":{"date-parts":[[2024,10,1]],"date-time":"2024-10-01T03:57:52Z","timestamp":1727755072000},"page":"3364","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Gender-Specific Prognostic Impact of Treosulfan Levels in High-Dose Chemotherapy for Multiple Myeloma"],"prefix":"10.3390","volume":"16","author":[{"given":"Alexander D.","family":"Heini","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, University Hospital Inselspital and University of Bern, 3010 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Kammermann","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, University Hospital Inselspital and University of Bern, 3010 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8771-947X","authenticated-orcid":false,"given":"Ulrike","family":"Bacher","sequence":"additional","affiliation":[{"name":"Department of Hematology and Central Hematology Laboratory, University Hospital Inselspital and University of Bern, 3010 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Jeker","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, University Hospital Inselspital and University of Bern, 3010 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Hayoz","sequence":"additional","affiliation":[{"name":"Center of Laboratory Medicine (ZLM), University Hospital Inselspital and University of Bern, 3010 Bern, Switzerland"},{"name":"Department of Clinical Chemistry, University Hospital Inselspital and University of Bern, 3010 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yolanda","family":"Aebi","sequence":"additional","affiliation":[{"name":"Center of Laboratory Medicine (ZLM), University Hospital Inselspital and University of Bern, 3010 Bern, Switzerland"},{"name":"Department of Clinical Chemistry, University Hospital Inselspital and University of Bern, 3010 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0889-8922","authenticated-orcid":false,"given":"Carlo R.","family":"Largiad\u00e8r","sequence":"additional","affiliation":[{"name":"Center of Laboratory Medicine (ZLM), University Hospital Inselspital and University of Bern, 3010 Bern, Switzerland"},{"name":"Department of Clinical Chemistry, University Hospital Inselspital and University of Bern, 3010 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1323-3116","authenticated-orcid":false,"given":"Henning","family":"Nilius","sequence":"additional","affiliation":[{"name":"Center of Laboratory Medicine (ZLM), University Hospital Inselspital and University of Bern, 3010 Bern, Switzerland"},{"name":"Department of Clinical Chemistry, University Hospital Inselspital and University of Bern, 3010 Bern, Switzerland"},{"name":"Graduate School for Health Sciences, University of Bern, 3012 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6055-5257","authenticated-orcid":false,"given":"Thomas","family":"Pabst","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, University Hospital Inselspital and University of Bern, 3010 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.annonc.2021.11.011","article-title":"Investigation of sex and gender differences in oncology gains momentum: ESMO announces the launch of a Gender Medicine Task Force","volume":"33","author":"Adjei","year":"2022","journal-title":"Ann. 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