B-Cell Regeneration Profile and Minimal Residual Disease Status in Bone Marrow of Treated Multiple Myeloma Patients
Robéria Mendonça de Pontes, Juan Flores-Montero, Luzalba Sanoja-Flores, Noemi Puig, Roberto J Pessoa de Magalhães, Alba Corral-Mateos, Anna Beatriz Salgado, Omar García-Sánchez, José Pérez-Morán, Maria-Victoria Mateos, Leire Burgos, Bruno Paiva, Jeroen Te Marvelde, Vincent H J van der Velden, Carlos Aguilar, Abelardo Bárez, Aranzazú García-Mateo, Jorge Labrador, Pilar Leoz, Carmen Aguilera-Sanz, Brian Durie, Jacques J M van Dongen, Angelo Maiolino, Elaine Sobral da Costa, Alberto Orfao
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/naïve 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.