Immunophenotyping of Paired Bone Marrow and Peripheral Blood: Implications for Monitoring Plasma Cell Disorders

Background: Although peripheral blood (PB) immunophenotyping is used to monitor immune reconstitution after transplant, there is almost no understanding of how closely the PB is correlated with the bone marrow (BM)—the tumor immune microenvironment (TIME)—in plasma cell disorders (PCD). The invasiveness of BM biopsies and spatial heterogeneity of cancer infiltration limit their use. Methods: To address this gap in knowledge, paired pre-treatment PB and BM aspirate (BMA) samples from 60 patients with PCDs were immunophenotyped with multicolor flow cytometry. Thirty lymphocyte populations and 11 ratios were quantified for each compartment. Abundance was expressed as median and BMA-PB correlation as Spearman’s correlation (ρ). Results: The largest differences in abundance are in CD8+ T cells: effector memory (+26% in BMA); and cells co-expressing ≥ 2 exhaustion-associated markers (+33% in BMA). Despite differential abundance, the BMA and PB of all markers are significantly correlated, with almost all having very strong or strong correlations, the strongest being the cytotoxic populations gamma-delta T cells (ρ = 0.95), CD8+ T cells (ρ = 0.96), and CD57+ NKT (ρ = 0.97). Exploratory stratified analyses revealed that most correlations remained strong even in subgroups defined by age, sex, obesity, symptom burden, purity of BMA sample, and days between PB and BMA sample. An illustrative single-patient exploratory analysis reveals that the focal lesion immune composition is closer to the PB than BMA. Conclusions: This study suggests that the PB provides insight into the PCD TIME, and further evaluation of PB immunophenotyping as a less-invasive approach for estimating selected BMA immune populations is warranted.