{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T19:38:19Z","timestamp":1790797099766,"version":"4.1.0"},"reference-count":30,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2021,9,30]],"date-time":"2021-09-30T00:00:00Z","timestamp":1632960000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100014139","name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer","doi-asserted-by":"publisher","award":["CB16\/12\/00369"],"award-info":[{"award-number":["CB16\/12\/00369"]}],"id":[{"id":"10.13039\/501100014139","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014139","name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer","doi-asserted-by":"publisher","award":["CB16\/12\/00400"],"award-info":[{"award-number":["CB16\/12\/00400"]}],"id":[{"id":"10.13039\/501100014139","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014139","name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer","doi-asserted-by":"publisher","award":["CB16\/12\/00233"],"award-info":[{"award-number":["CB16\/12\/00233"]}],"id":[{"id":"10.13039\/501100014139","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014139","name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer","doi-asserted-by":"publisher","award":["CB16\/12\/00284"],"award-info":[{"award-number":["CB16\/12\/00284"]}],"id":[{"id":"10.13039\/501100014139","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI15\/01956"],"award-info":[{"award-number":["PI15\/01956"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI15\/02049"],"award-info":[{"award-number":["PI15\/02049"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI15\/02062"],"award-info":[{"award-number":["PI15\/02062"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI18\/01709"],"award-info":[{"award-number":["PI18\/01709"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI18\/01673"],"award-info":[{"award-number":["PI18\/01673"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Whereas, in most patients with multiple myeloma (MM), achieving undetectable MRD anticipates a favorable outcome, some others relapse shortly afterwards. Although one obvious explanation for this inconsistency is the use of nonrepresentative marrow samples due to hemodilution, there is no guidance on how to evaluate this issue. Methods: Since B-cell precursors, mast cells and nucleated red blood cells are normally absent in peripheral blood, we analyzed them in 1404 bone marrow (BM) aspirates obtained in numerous disease settings and in 85 healthy adults (HA). Results: First, we confirmed the systematic detection of the three populations in HA, as well as the nonreduced numbers with aging. Pairwise comparisons between HA and MM patients grouped according to age and treatment showed significant variability, suggesting that hemodilution should be preferably evaluated with references obtained from patients treated with identical regimens. Leveraging the MRD results from 118 patients, we showed that a comparison with HA of similar age could also inform on potential hemodilution. Conclusions: Our study supports the routine assessment of BM cellularity to evaluate hemodilution, since reduced BM-specific cell types as compared to reference values (either treatment-specific or from HA if the former are unavailable) could indicate hemodilution and a false-negative MRD result.<\/jats:p>","DOI":"10.3390\/cancers13194924","type":"journal-article","created":{"date-parts":[[2021,9,30]],"date-time":"2021-09-30T10:22:42Z","timestamp":1632997362000},"page":"4924","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Reference Values to Assess Hemodilution and Warn of Potential False-Negative Minimal Residual Disease Results in Myeloma"],"prefix":"10.3390","volume":"13","author":[{"given":"Noem\u00ed","family":"Puig","sequence":"first","affiliation":[{"name":"Hematology Department, Hospital Universitario de Salamanca (HUSAL), IBSAL, IBMCC (USAL-CSIC), CIBERONC (CB16\/12\/00233), 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1119-4387","authenticated-orcid":false,"given":"Juan","family":"Flores-Montero","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Research of Salamanca (IBSAL), Centro de Investigaci\u00f3n Biom\u00e9dica en Red C\u00e1ncer CIBERONC (CB16\/12\/00400), Cancer Research Center (IBMCC, USAL-CSIC), Cytometry Service (NUCLEUS) and Department of Medicine, University of Salamanca, 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0998-2496","authenticated-orcid":false,"given":"Leire","family":"Burgos","sequence":"additional","affiliation":[{"name":"Cl\u00ednica Universidad de Navarra, Centro de Investigaci\u00f3n Aplicada (CIMA), Instituto de Investigaci\u00f3n Sanitaria de Navarra (IDISNA), CIBERONC (CB16\/12\/00369), 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5851-3720","authenticated-orcid":false,"given":"Mar\u00eda-Teresa","family":"Cedena","sequence":"additional","affiliation":[{"name":"Hospital Universitario 12 de Octubre, CIBERONC (CB16\/12\/00369), 28041 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lourdes","family":"Cord\u00f3n","sequence":"additional","affiliation":[{"name":"Grupo de Investigaci\u00f3n en Hematolog\u00eda, Instituto de Investigaci\u00f3n Sanitaria La Fe (IIS La Fe), CIBERONC (CB16\/12\/00284), 46026 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9-Juan","family":"P\u00e9rez","sequence":"additional","affiliation":[{"name":"Hematology Department, Hospital Universitario de Salamanca (HUSAL), IBSAL, IBMCC (USAL-CSIC), CIBERONC (CB16\/12\/00233), 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9275-7793","authenticated-orcid":false,"given":"Luzalba","family":"Sanoja-Flores","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine of Seville, Department of Hematology, University Hospital Virgen del Roc\u00edo of the Consejo Superior de Investigaciones Cient\u00edficas (CSIC), University of Seville, Seville, Spain & CIBERONC (CB16\/12\/00480), Instituto Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Manrique","sequence":"additional","affiliation":[{"name":"Cl\u00ednica Universidad de Navarra, Centro de Investigaci\u00f3n Aplicada (CIMA), Instituto de Investigaci\u00f3n Sanitaria de Navarra (IDISNA), CIBERONC (CB16\/12\/00369), 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Rodr\u00edguez-Otero","sequence":"additional","affiliation":[{"name":"Cl\u00ednica Universidad de Navarra, Centro de Investigaci\u00f3n Aplicada (CIMA), Instituto de Investigaci\u00f3n Sanitaria de Navarra (IDISNA), CIBERONC (CB16\/12\/00369), 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Rosi\u00f1ol","sequence":"additional","affiliation":[{"name":"Hematology Department, IDIBAPS, Hospital Clinic, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7908-0063","authenticated-orcid":false,"given":"Joaqu\u00edn","family":"Mart\u00ednez-L\u00f3pez","sequence":"additional","affiliation":[{"name":"Hospital Universitario 12 de Octubre, CIBERONC (CB16\/12\/00369), 28041 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2390-1218","authenticated-orcid":false,"given":"Mar\u00eda-Victoria","family":"Mateos","sequence":"additional","affiliation":[{"name":"Hematology Department, Hospital Universitario de Salamanca (HUSAL), IBSAL, IBMCC (USAL-CSIC), CIBERONC (CB16\/12\/00233), 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3393-9570","authenticated-orcid":false,"given":"Juan-Jos\u00e9","family":"Lahuerta","sequence":"additional","affiliation":[{"name":"Hospital Universitario 12 de Octubre, CIBERONC (CB16\/12\/00369), 28041 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joan","family":"Blad\u00e9","sequence":"additional","affiliation":[{"name":"Hematology Department, IDIBAPS, Hospital Clinic, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9183-4857","authenticated-orcid":false,"given":"Jes\u00fas F.","family":"San Miguel","sequence":"additional","affiliation":[{"name":"Cl\u00ednica Universidad de Navarra, Centro de Investigaci\u00f3n Aplicada (CIMA), Instituto de Investigaci\u00f3n Sanitaria de Navarra (IDISNA), CIBERONC (CB16\/12\/00369), 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0007-7230","authenticated-orcid":false,"given":"Alberto","family":"Orfao","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Research of Salamanca (IBSAL), Centro de Investigaci\u00f3n Biom\u00e9dica en Red C\u00e1ncer CIBERONC (CB16\/12\/00400), Cancer Research Center (IBMCC, USAL-CSIC), Cytometry Service (NUCLEUS) and Department of Medicine, University of Salamanca, 37007 Salamanca, 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Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1186\/s13045-020-00911-4","article-title":"Measurable residual disease in multiple myeloma: Ready for clinical practice?","volume":"13","author":"Burgos","year":"2020","journal-title":"J. Hematol. Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1038\/s41375-020-01012-4","article-title":"International harmonization in performing and reporting minimal residual disease assessment in multiple myeloma trials","volume":"35","author":"Costa","year":"2021","journal-title":"Leukemia"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/S0140-6736(19)31240-1","article-title":"Bortezomib, thalidomide, and dexamethasone with or without daratumumab before and after autologous stem-cell transplantation for newly diagnosed multiple myeloma (CASSIOPEIA): A randomised, open-label, phase 3 study","volume":"394","author":"Moreau","year":"2019","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1056\/NEJMoa1714678","article-title":"Daratumumab plus Bortezomib, Melphalan, and Prednisone for Untreated Myeloma","volume":"378","author":"Mateos","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1953","DOI":"10.1182\/blood-2018-09-874396","article-title":"Carfilzomib or bortezomib with melphalan-prednisone for transplant-ineligible patients with newly diagnosed multiple myeloma","volume":"133","author":"Facon","year":"2019","journal-title":"Blood"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"5988","DOI":"10.1182\/bloodadvances.2020002827","article-title":"A large meta-analysis establishes the role of MRD negativity in long-term survival outcomes in patients with multiple myeloma","volume":"4","author":"Munshi","year":"2020","journal-title":"Blood Adv."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2104","DOI":"10.1056\/NEJMoa1817249","article-title":"Daratumumab plus Lenalidomide and Dexamethasone for Untreated Myeloma","volume":"380","author":"Facon","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1056\/NEJMoa1607751","article-title":"Daratumumab, Lenalidomide, and Dexamethasone for Multiple Myeloma","volume":"375","author":"Dimopoulos","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1056\/NEJMoa1611750","article-title":"Lenalidomide, Bortezomib, and Dexamethasone with Transplantation for Myeloma","volume":"376","author":"Attal","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2218","DOI":"10.1182\/blood.2019002610","article-title":"Blood monitoring of circulating tumor plasma cells by next generation flow in multiple myeloma after therapy","volume":"134","author":"Puig","year":"2019","journal-title":"Blood"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3295","DOI":"10.1182\/bloodadvances.2020002037","article-title":"Clinical value of measurable residual disease testing for assessing depth, duration, and direction of response in multiple myeloma","volume":"4","author":"Wong","year":"2020","journal-title":"Blood Adv."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2456","DOI":"10.1182\/blood-2018-06-858613","article-title":"Minimal residual disease negativity using deep sequencing is a major prognostic factor in multiple myeloma","volume":"132","author":"Perrot","year":"2018","journal-title":"Blood"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1200\/JCO.19.01231","article-title":"Measurable residual disease by next-generation flow cytometry in multiple myeloma","volume":"38","author":"Paiva","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e300","DOI":"10.1097\/HS9.0000000000000300","article-title":"Impact of Minimal Residual Disease Detection by Next-Generation Flow Cytometry in Multiple Myeloma Patients with Sustained Complete Remission after Frontline Therapyfile:\/\/\/Users\/noemipuig\/Documents\/CALIDAD DE LAS MUESTRAS\/for CANCERS\/Martinez-Lopez Blood","volume":"3","author":"Terpos","year":"2019","journal-title":"HemaSphere"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2911","DOI":"10.1200\/JCO.2017.72.2975","article-title":"Prospective Evaluation of Magnetic Resonance Imaging and [18F] Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography at Diagnosis and Before Maintenance Therapy in Symptomatic PatientsWith Multiple Myeloma Included in the IFM\/DFCI 2009 Trial","volume":"35","author":"Moreau","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1038\/s41375-018-0329-0","article-title":"Combination of flow cytometry and functional imaging for monitoring of residual disease in myeloma","volume":"33","author":"Rasche","year":"2019","journal-title":"Leukemia"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.1182\/blood.2019000241","article-title":"Bortezomib, lenalidomide, and dexamethasone as induction therapy prior to autologous transplant in multiple myeloma","volume":"134","author":"Oriol","year":"2019","journal-title":"Blood"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/s41408-021-00490-8","article-title":"Lenalidomide and dexamethasone with or without clarithromycin in patients with multiple myeloma ineligible for autologous transplant: A randomized trial","volume":"11","author":"Puig","year":"2021","journal-title":"Blood Cancer J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2094","DOI":"10.1038\/leu.2017.29","article-title":"Next Generation Flow for highly sensitive and standardized detection of minimal residual disease in multiple myeloma","volume":"31","author":"Paiva","year":"2017","journal-title":"Leukemia"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3165","DOI":"10.1182\/blood-2016-03-705319","article-title":"Minimal residual disease monitoring and immune profiling in multiple myeloma in elderly patients","volume":"127","author":"Paiva","year":"2016","journal-title":"Blood"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1182\/blood-2015-08-666537","article-title":"Sequential vs. alternating administration of VMP and Rd in elderly patients with newly diagnosed MM","volume":"127","author":"Mateos","year":"2016","journal-title":"Blood"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1038\/s41408-018-0153-9","article-title":"Next generation flow for minimally-invasive blood characterization of MGUS and multiple myeloma at diagnosis based on circulating tumor plasma cells (CTPC)","volume":"8","author":"Paiva","year":"2018","journal-title":"Blood Cancer J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1038\/leu.2017.320","article-title":"Prognostic value of antigen expression in multiple myeloma: A PETHEMA\/GEM study on 1265 patients enrolled in four consecutive clinical trials","volume":"32","author":"Arana","year":"2018","journal-title":"Leukemia"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.1038\/s41375-018-0308-5","article-title":"Flow cytometry for fast screening and automated risk assessment in systemic light-chain amyloidosis","volume":"33","author":"Puig","year":"2019","journal-title":"Leukemia"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2358","DOI":"10.3324\/haematol.2020.247015","article-title":"Multiple myeloma: The (r) evolution of current therapy and a glance into the future","volume":"105","author":"Gulla","year":"2020","journal-title":"Haematologica"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1182\/blood-2017-06-740944","article-title":"CD38 antibodies in multiple myeloma: Back to the future","volume":"131","author":"Richardson","year":"2018","journal-title":"Blood"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1038\/leu.2009.236","article-title":"Mechanism of action of immunomodulatory drugs (IMiDS) in multiple myeloma","volume":"24","author":"Quach","year":"2010","journal-title":"Leukemia"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1172\/JCI129205","article-title":"Immunotherapy of multiple myeloma","volume":"130","author":"Minnie","year":"2020","journal-title":"J. Clin. Investig."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1726","DOI":"10.1056\/NEJMoa1817226","article-title":"Anti-BCMA CAR T-Cell Therapy bb2121 in Relapsed or Refractory Multiple Myeloma","volume":"380","author":"Raje","year":"2019","journal-title":"N. Engl. J. Med."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/19\/4924\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:07:52Z","timestamp":1760166472000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/19\/4924"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,30]]},"references-count":30,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2021,10]]}},"alternative-id":["cancers13194924"],"URL":"https:\/\/doi.org\/10.3390\/cancers13194924","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,30]]}}}