B-Cell Regeneration Profile and Minimal Residual Disease Status in Bone Marrow of Treated Multiple Myeloma Patients

Año de publicación
2021
Autores
de Pontes, RM; Flores-Montero, J; Sanoja-Flores, L; Puig, N; de Magalhaes, RPJ; Corral-Mateos, A; Salgado, AB; Garcia-Sanchez, O; Perez-Moran, J; Mateos, MV; Burgos, L; Paiva, B; te Marvelde, J; van der Velden, VHJ; Aguilar, C; Barez, A; Garcia-Mateo, A; Labrador, J; Leoz, P; Aguilera-Sanz, C; Durie, B; van Dongen, JJM; Maiolino, A; da Costa, ES; Orfao, A
Grupo de Trabajo
Revista
CANCERS
Volumen
13
Article number
1704
Issue
7

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.