{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T23:08:13Z","timestamp":1781305693739,"version":"3.54.1"},"reference-count":55,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,4,3]],"date-time":"2021-04-03T00:00:00Z","timestamp":1617408000000},"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\/00400, CB16\/12\/00233, CB16\/12\/00369, CB16\/12\/00489, CB16\/12\/00480"],"award-info":[{"award-number":["CB16\/12\/00400, CB16\/12\/00233, CB16\/12\/00369, CB16\/12\/00489, CB16\/12\/00480"]}],"id":[{"id":"10.13039\/501100014139","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior (CAPES\/DGPU)","award":["000281\/2016-06"],"award-info":[{"award-number":["000281\/2016-06"]}]},{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior (CAPES-PROEX)","award":["641\/2018"],"award-info":[{"award-number":["641\/2018"]}]},{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico of Brazil (CNPQ)","award":["400194\/2014-7"],"award-info":[{"award-number":["400194\/2014-7"]}]},{"name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado do Rio de Janeiro of Brazil (FAPERJ)","award":["E26\/110.105\/2014, E26\/102.191\/2013 and E01\/200\/537\/2018"],"award-info":[{"award-number":["E26\/110.105\/2014, E26\/102.191\/2013 and E01\/200\/537\/2018"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>B-cell regeneration during therapy has been considered as a strong prognostic factor in multiple myeloma (MM). However, the effects of therapy and hemodilution in bone marrow (BM) B-cell recovery have not been systematically evaluated during follow-up. MM (n = 177) and adult (\u226550y) healthy donor (HD; n = 14) BM samples were studied by next-generation flow (NGF) to simultaneously assess measurable residual disease (MRD) and residual normal B-cell populations. BM hemodilution was detected in 41 out of 177 (23%) patient samples, leading to lower total B-cell, B-cell precursor (BCP) and normal plasma cell (nPC) counts. Among MM BM, decreased percentages (vs. HD) of BCP, transitional\/na\u00efve B-cell (TBC\/NBC) and nPC populations were observed at diagnosis. BM BCP increased after induction therapy, whereas TBC\/NBC counts remained abnormally low. At day+100 postautologous stem cell transplantation, a greater increase in BCP with recovered TBC\/NBC cell numbers but persistently low memory B-cell and nPC counts were found. At the end of therapy, complete response (CR) BM samples showed higher CD19\u2212 nPC counts vs. non-CR specimens. MRD positivity was associated with higher BCP and nPC percentages. Hemodilution showed a negative impact on BM B-cell distribution. Different BM B-cell regeneration profiles are present in MM at diagnosis and after therapy with no significant association with patient outcome.<\/jats:p>","DOI":"10.3390\/cancers13071704","type":"journal-article","created":{"date-parts":[[2021,4,3]],"date-time":"2021-04-03T22:03:36Z","timestamp":1617487416000},"page":"1704","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["B-Cell Regeneration Profile and Minimal Residual Disease Status in Bone Marrow of Treated Multiple Myeloma Patients"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3608-8254","authenticated-orcid":false,"given":"Rob\u00e9ria","family":"Mendon\u00e7a de Pontes","sequence":"first","affiliation":[{"name":"Internal Medicine Postgraduate Program, Faculty of Medicine, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro 21941-617, Brazil"},{"name":"Cytometry Service, Institute of Paediatrics and Puericultura Martag\u00e3o Gesteira (IPPMG), Faculty of Medicine, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro 21941-912, Brazil"}],"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":"Translational and Clinical Research Program, Cancer Research Center (IBMCC, USAL-CSIC), Cytometry Service (NUCLEUS) and Department of Medicine, University of Salamanca, Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer (CIBERONC) (CB16\/12\/00400, CB16\/12\/00233, CB16\/12\/00369, CB16\/12\/00489 and CB16\/12\/00480), Instituto Carlos III, 28029 Madrid, 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":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer (CIBERONC) (CB16\/12\/00400, CB16\/12\/00233, CB16\/12\/00369, CB16\/12\/00489 and CB16\/12\/00480), Instituto Carlos III, 28029 Madrid, Spain"},{"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, 41013 Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noemi","family":"Puig","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer (CIBERONC) (CB16\/12\/00400, CB16\/12\/00233, CB16\/12\/00369, CB16\/12\/00489 and CB16\/12\/00480), Instituto Carlos III, 28029 Madrid, Spain"},{"name":"Service of Hematology, University Hospital of Salamanca (USAL) and IBSAL, 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto J.","family":"Pessoa de Magalh\u00e3es","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University Hospital Clementino Fraga Filho, Faculty of Medicine, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro 21941-617, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alba","family":"Corral-Mateos","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Program, Cancer Research Center (IBMCC, USAL-CSIC), Cytometry Service (NUCLEUS) and Department of Medicine, University of Salamanca, Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer (CIBERONC) (CB16\/12\/00400, CB16\/12\/00233, CB16\/12\/00369, CB16\/12\/00489 and CB16\/12\/00480), Instituto Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Beatriz","family":"Salgado","sequence":"additional","affiliation":[{"name":"Internal Medicine Postgraduate Program, Faculty of Medicine, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro 21941-617, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar","family":"Garc\u00eda-S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer (CIBERONC) (CB16\/12\/00400, CB16\/12\/00233, CB16\/12\/00369, CB16\/12\/00489 and CB16\/12\/00480), Instituto Carlos III, 28029 Madrid, Spain"},{"name":"Service of Hematology, University Hospital of Salamanca (USAL) and IBSAL, 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9","family":"P\u00e9rez-Mor\u00e1n","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer (CIBERONC) (CB16\/12\/00400, CB16\/12\/00233, CB16\/12\/00369, CB16\/12\/00489 and CB16\/12\/00480), Instituto Carlos III, 28029 Madrid, Spain"},{"name":"Service of Hematology, University Hospital of Salamanca (USAL) and IBSAL, 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2390-1218","authenticated-orcid":false,"given":"Maria-Victoria","family":"Mateos","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer (CIBERONC) (CB16\/12\/00400, CB16\/12\/00233, CB16\/12\/00369, CB16\/12\/00489 and CB16\/12\/00480), Instituto Carlos III, 28029 Madrid, Spain"},{"name":"Service of Hematology, University Hospital of Salamanca (USAL) and IBSAL, 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leire","family":"Burgos","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer (CIBERONC) (CB16\/12\/00400, CB16\/12\/00233, CB16\/12\/00369, CB16\/12\/00489 and CB16\/12\/00480), Instituto Carlos III, 28029 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n M\u00e9dica Aplicada (CIMA), Instituto de Investigaci\u00f3n Sanitaria de Navarra (IDISNA), Cl\u00ednica Universidad de Navarra, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1977-3815","authenticated-orcid":false,"given":"Bruno","family":"Paiva","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer (CIBERONC) (CB16\/12\/00400, CB16\/12\/00233, CB16\/12\/00369, CB16\/12\/00489 and CB16\/12\/00480), Instituto Carlos III, 28029 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n M\u00e9dica Aplicada (CIMA), Instituto de Investigaci\u00f3n Sanitaria de Navarra (IDISNA), Cl\u00ednica Universidad de Navarra, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeroen","family":"te Marvelde","sequence":"additional","affiliation":[{"name":"Department of Immunology, Erasmus MC, (EMC) University Medical Center Rotterdam, 3015 GA Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent H. J.","family":"van der Velden","sequence":"additional","affiliation":[{"name":"Department of Immunology, Erasmus MC, (EMC) University Medical Center Rotterdam, 3015 GA Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5225-6687","authenticated-orcid":false,"given":"Carlos","family":"Aguilar","sequence":"additional","affiliation":[{"name":"Department of Hematology, Hospital General de Santa B\u00e1rbara, 42005 Soria, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8982-6105","authenticated-orcid":false,"given":"Abelardo","family":"B\u00e1rez","sequence":"additional","affiliation":[{"name":"Department of Hematology, Complejo Asistencial de \u00c1vila, 05071 \u00c1vila, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aranzaz\u00fa","family":"Garc\u00eda-Mateo","sequence":"additional","affiliation":[{"name":"Department of Hematology, Complejo Asistencial de Segovia, 40002 Segovia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3696-0287","authenticated-orcid":false,"given":"Jorge","family":"Labrador","sequence":"additional","affiliation":[{"name":"Department of Hematology and Research Unit, Hospital Universitario de Burgos, 09006 Burgos, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pilar","family":"Leoz","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer (CIBERONC) (CB16\/12\/00400, CB16\/12\/00233, CB16\/12\/00369, CB16\/12\/00489 and CB16\/12\/00480), Instituto Carlos III, 28029 Madrid, Spain"},{"name":"Service of Hematology, University Hospital of Salamanca (USAL) and IBSAL, 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Aguilera-Sanz","sequence":"additional","affiliation":[{"name":"Department of Hematology, Hospital El Bierzo, 24404 Ponferrada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Durie","sequence":"additional","affiliation":[{"name":"Cedars-Sinai Samuel Oschin Cancer Center, Los Angeles, CA 90048, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques J. M.","family":"van Dongen","sequence":"additional","affiliation":[{"name":"Department of Immunology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo","family":"Maiolino","sequence":"additional","affiliation":[{"name":"Internal Medicine Postgraduate Program, Faculty of Medicine, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro 21941-617, Brazil"},{"name":"Department of Internal Medicine, University Hospital Clementino Fraga Filho, Faculty of Medicine, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro 21941-617, Brazil"},{"name":"Americas Centro de Oncologia Integrado, Rio de Janeiro 22290-030, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5340-5816","authenticated-orcid":false,"given":"Elaine","family":"Sobral da Costa","sequence":"additional","affiliation":[{"name":"Internal Medicine Postgraduate Program, Faculty of Medicine, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro 21941-617, Brazil"},{"name":"Cytometry Service, Institute of Paediatrics and Puericultura Martag\u00e3o Gesteira (IPPMG), Faculty of Medicine, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro 21941-912, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0007-7230","authenticated-orcid":false,"given":"Alberto","family":"Orfao","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Program, Cancer Research Center (IBMCC, USAL-CSIC), Cytometry Service (NUCLEUS) and Department of Medicine, University of Salamanca, Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer (CIBERONC) (CB16\/12\/00400, CB16\/12\/00233, CB16\/12\/00369, CB16\/12\/00489 and CB16\/12\/00480), Instituto Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1860","DOI":"10.1056\/NEJMra041875","article-title":"Multiple myeloma","volume":"351","author":"Kyle","year":"2004","journal-title":"N. 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