INTRODUCTION AND OBJECTIVE: B-cell recovery has been reported as a unique feature of patients who attain long-term disease control in multiple myeloma (MM). The kinetics of B-cell reconstitution in bone marrow (BM) from MM patients during treatment was described but the recovery of B-cell subsets in peripheral blood (PB) after therapy remains an investigation. The goal of this study was to describe B-cell subsets in PB vs. BM from MM patients at D+100 after autologous stem cell transplantation (ASCT) and their potential relationship with measurable residual disease (MRD). MATERIAL AND METHODS: A total of 152 paired BM and PB samples from 76 active MM patients were studied at D+100 post-ASCT, receiving induction regimens based on immunomodulatory drugs and/or proteasome inhibitors as first-line therapy, followed by high dose melphalan prior ASCT. Age-matched healthy donors (HD) were studied as controls. All samples were processed within 24h after they had been collected at two different centers (UFRJ, n= 88; USAL, n= 64), following the EuroFlow standard operating procedures and stained with EuroFlow NGF MM MRD two-8 color antibody combinations. B-cell subsets identified: B-cell precursors (BCP – CD19+CD38highCD45loCD81hi), transitional (TR)/naive B-cells (CD19+CD45+CD38-/loCD27-cyIg+), memory B-cells (CD19+CD45+CD38-/loCD27+ cyIg+) and normal/polyclonal plasma cells (nPC – CD38hiCD138lo/hetCD45-/hetCD81hetCD56-/+cyIg+). RESULTS AND CONCLUSIONS: Fifty patients (66%) had MRD+. From these, 7/50 (14%) still presented circulating tumor plasma cells (CTPC) detectable in PB. All BM from MM patients had B-cell precursors (BCP) percentages above normal levels, while memory B-cells and nPC were under normal frequencies. However, MRD+CTPC+ patients had significantly lower frequencies of nPC CD19- (long-lived PC) in BM compared to MRD+or-/CTPC- patients. In PB, TR/naive B-cells recovery to normal values, but memory B-cells counts were significantly reduced in all groups of MM patients vs. HD. PB nPC CD19+ (plasmablasts) from MRD+or-/CTPC- patients were comparable to normal counts but significantly decreased in MRD+CTPC+. No significant association between PFS and B-cell counts in PB was observed. Relapses occurred in 28/76 (37%) of patients, 8/28 (29%) MRD-CTPC-, 16/28 (57%) MRD+CTPC- and 4/28 (14%) MRD+CTPC+. Mortality was 14% (11/76), 8/11 (72%) MRD+ (6 CTPC- and 2 CTPC+) and 3/11 (27%) MRD-CTPC- in 19 months (m) of median follow-up. MRD+CTPC+ patients had a significantly shorter PFS, 9m vs. 28m in MRD+CTPC- and not reached in MRD-CTPC- patients. Similarly, patients who achieved CR/sCR had a median PFS of 9m in MRD+CTPC+ vs. 28m in MRD+CTPC- and 36m in MRD-CTPC- patients. In the present study, the presence of CTPC at D+100 post-ASCT was associated with both: poor recovery of nPC counts in PB and a worse PFS. This seems to reinforce that cPC clearance post-ASCT would increase the availability of BM niches leading to a recovery of normal B cell maturation.