{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T19:25:29Z","timestamp":1783797929435,"version":"3.55.0"},"reference-count":30,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2024,7,29]],"date-time":"2024-07-29T00:00:00Z","timestamp":1722211200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>Multiple myeloma (MM) first-line treatment algorithms include immuno-chemotherapy (ICT) induction, high-dose chemotherapy (HDCT) and autologous stem cell transplant (ASCT) consolidation, followed by lenalidomide maintenance. After these initial therapies, most patients suffer a disease relapse and require subsequent treatment lines including ICT, additional HDCT and ASCT, or novel immunotherapies. The presence of somatic mutations in peripheral blood cells has been associated with adverse outcomes in a variety of hematological malignancies. Nonsense and frameshift mutations in the PPM1D gene, a frequent driver alteration in clonal hematopoiesis (CH), lead to the gain-of-function of Wip1 phosphatase, which may impair the p53-dependent G1 checkpoint and promote cell proliferation. Here, we determined the presence of PPM1D gene mutations in peripheral blood cells of 75 subsequent myeloma patients in remission after first or second HDCT\/ASCT. The prevalence of truncating PPM1D gene mutations emerged at 1.3% after first HDCT\/ASCT, and 7.3% after second HDCT\/ASCT, with variant allele frequencies (VAF) of 0.01 to 0.05. Clinical outcomes were inferior in the PPM1D-mutated (PPM1Dmut) subset with median progression-free survival (PFS) of 15 vs. 37 months (p = 0.0002) and median overall survival (OS) of 36 vs. 156 months (p = 0.001) for the PPM1Dmut and PPM1Dwt population, respectively. Our data suggest that the occurrence of PPM1D gene mutations in peripheral blood cells correlates with inferior outcomes after ASCT in patients with multiple myeloma.<\/jats:p>","DOI":"10.3390\/cimb46080484","type":"journal-article","created":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T15:24:16Z","timestamp":1722957856000},"page":"8197-8208","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Rising Prevalence of Low-Frequency PPM1D Gene Mutations after Second HDCT in Multiple Myeloma"],"prefix":"10.3390","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3128-1573","authenticated-orcid":false,"given":"Katja","family":"Seipel","sequence":"first","affiliation":[{"name":"Department for Biomedical Research, University of Bern, 3008 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuria Z.","family":"Veglio","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, University Hospital 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":"Department of Clinical Chemistry, 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 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, University Hospital Bern, 3010 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 Bern, 3010 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2962","DOI":"10.1182\/blood-2007-10-078022","article-title":"Multiple Myeloma","volume":"111","author":"Kyle","year":"2008","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1056\/NEJMra1011442","article-title":"Multiple Myeloma","volume":"364","author":"Palumbo","year":"2011","journal-title":"N. 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