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

Abstract

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.

Immunophenotypic Characteristics of Bone Marrow Microenvironment Cellular Composition at the Biochemical Progression of Multiple Myeloma

“…It should be noted that we report the relative distribution of the populations as a percentage of BM where cell numbers might be influenced by the recovery or changes of other populations. Nevertheless, the change in the composition of B-cell subpopulations noted in patients in BR confirms the gradual impairment of the immune system seen in both clinical recurrence and in newly diagnosed MM patients [8,21].…”

“…In our study, the BM immune profile of MRDneg patients in CR was assessed after the first treatment line with ASCT consolidation, at the interval of 100-180 days after the transplantation procedure. This does not fully correspond to the profile of healthy donors due to the increased or often incomplete regeneration after transplantation, but it may to some extent reflect the immunological status of the control over neoplastic cells [21]. However, in most patients, post-ASCT state of the myeloma-immune equilibrium is followed by immunological escape and subsequent progression, facilitated by multiple factors including alternations in cytokine production, T-cells exhaustion, and accumulation of macrophages protecting MM cells from apoptosis [22,23].…”

“…They highlighted the need to carefully design experiments that can lead toward a better understanding of the effects of treatment regimens on the anti-myeloma response [38]. It is worth noting that distribution of different subpopulation of BM cells might depend not only on prior treatment but also may differ in separate prognostic groups and may change during recovery from therapy [13,21,39]. The relapse status we referred not to healthy donors but to the MRD-negative status, which, from our point of view, is closest to the actual condition of the BM microenvironment of patients after effective treatment and which is modulated in the disease-progression process.…”

Development of a 27‐color panel for the detection of measurable residual disease in patients diagnosed with acute myeloid leukemia

“…Secondly, the degree of hemodilution can be assessed by incorporating markers used for defining immune cells that should only be found in bone marrow. In this regard, the presence of mast cells (bright for CD117) and hematogones (dim for CD45, CD38, CD10 and positive for CD19), and the ratio of immature/mature neutrophils based on CD16 intensity can be used [35,36]. This is not easily achievable in traditional 8-10 color methods without adding additional tubes.…”