Molecular disease in plasma vs leukocytes. (A) By analyzing cellular and plasma fractions isolated from 82 samples acquired from 25 patients, we found that clonotype was more abundant per million genome equivalent (G.E.) in the plasma fraction. This included 2 types of cellular fractions: peripheral blood mononuclear cells (blue circles) and plasma-depleted whole blood (purple squares). For 11 samples from 7 different patients, tumor clonotype was detected solely within the plasma fraction and not the cellular fraction, including 2 samples taken at the time of CNS relapse. A total of 7 samples from 4 patients had the tumor clonotype detected only in the cellular fraction and not in the plasma. (B) Thirty-four paired samples with both plasma Ig-HTS and LDH and (C) 26 paired samples with both cellular Ig-HTS and LDH at time points of overt disease (diagnosis or progression/relapse). Plasma Ig-HTS was significantly more sensitive than LDH (88% vs 59%, P = .01). Cellular Ig-HTS was not more sensitive than LDH (62% vs 59%, P = 1.0). (D) Detection of molecular disease in the plasma fraction of blood was significantly correlated with MTV as measured by PET/CT scans (n = 32) at paired time points across 27 patients (P = .002, Pearson r = 0.53). No significant correlation was seen between MTV and cellular Ig-HTS. Plasma samples were taken within 28 days of PET/CT scan (median, 1.5 days).