期刊
CANCERS
卷 13, 期 7, 页码 -出版社
MDPI
DOI: 10.3390/cancers13071704
关键词
multiple myeloma; B-cell regeneration; hemodilution; measurable residual disease; immunophenotyping
类别
资金
- International Myeloma Foundation-Black Swan Research Initiative
- EuroFlow Consortium [LSHB-CT-2006-018708]
- Centro de Investigacion Biomedica en Red de Cancer (CIBER-ONC) [CB16/12/00400, CB16/12/00233, CB16/12/00369, CB16/12/00489, CB16/12/00480]
- Centro de Investigacion Biomedica en Red de Cancer (Instituto de Salud Carlos III, Ministerio de Economia y Competitividad, Madrid, Spain) [CB16/12/00400, CB16/12/00233, CB16/12/00369, CB16/12/00489, CB16/12/00480]
- Centro de Investigacion Biomedica en Red de Cancer (FONDOS FEDER) [CB16/12/00400, CB16/12/00233, CB16/12/00369, CB16/12/00489, CB16/12/00480]
- Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior-CAPES (Brasilia/Brazil)
- Direccion General de Politicas Universitarias (DGPU)-Ministerio de Educacion, Cultura y Deportes (Madrid/Spain) [DGPU 311/15]
- Fundacao de Amparo a Pesquisa do Estado do Rio de Janeiro of Brazil (FAPERJ) [E26/110.105/2014, E26/102.191/2013, E01/200/537/2018]
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico of Brazil (CNPQ) [400194/2014-7]
- Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES/DGPU), Brazil [000281/2016-06, CAPES/PROEX 641/2018]
The study found that B-cell regeneration during therapy in multiple myeloma patients is not significantly associated with patient outcomes, and therapy and hemodilution impact bone marrow B-cell recovery to some extent.
Simple Summary B-cell regeneration during therapy has been associated with the outcome of multiple myeloma (MM) patients. However, the effects of therapy and hemodilution in bone marrow (BM) B-cell recovery have not been systematically evaluated. Here, we show that hemodilution is present in a significant fraction of MM BM samples, leading to lower total B-cell, B-cell precursor (BCP), and normal plasma cell (nPC) counts. Among MM BM samples, decreased percentages (vs. healthy donors) of BCP, transitional/naive B-cell (TBC/NBC) and nPC populations were observed at diagnosis. BM BCP, but not TBC/NBC, increased after induction therapy. At day+100 post-autolo-gous stem cell transplantation, a greater increase in BCP with recovered TBC/NBC 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(-) nPC counts vs. non-CR specimens with no clear association between BM B-cell regeneration profiles and patient outcomes. 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 (>= 50y) 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/naive 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(-) 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.
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