Salgado, A.B. (Anna Beatriz)

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    B-cell regeneration profile and minimal residual disease status in bone marrow of treated multiple myeloma patients
    (2021) Aguilera-Sanz, C. (Carmen); Durie, B. (B.); Montero, J. (Juan); Marvelde, J. (Jeroen) te; Aguilar, C. (Carlos); Pérez-Morán, J. (José); García-Mateo, A. (A.); Mendonca-de-Pontes, R. (Robéria); Corral-Mateos, A. (A.); Orfao, A. (Alberto); Maiolino, A. (Angelo); Mateos, M.V. (María Victoria); Barez, A. (A.); Leoz, P. (Pilar); Sobral-da-Costa, E. (Elaine); Puig, N. (Noemí); Labrador, J. (Jorge); Burgos, L. (Leire); García-Sanchez, O. (O.); Dongen, J.J.M. (Jacques J. M.) van; Paiva, B. (Bruno); EuroFlow-Consortium; Sanoja-Flores, L. (L.); Salgado, A.B. (Anna Beatriz); Pessoa-de-Magalhaes, R.J. (Roberto J.); Velden, V.H.J. (Vicent H. J.) van der
    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.