Limits of disease detection during therapy. (A) Tumor clonotype was detected at varying levels within 1 mL of plasma from 7 of 8 patients before treatment. At an interim time point after 4 cycles of R-CHOP, disease was not detectable in any patient (red circles, detectable molecular disease; gray circles, undetectable molecular disease; red patients, detectable disease on PET/CT; black patients, no detectable disease on PET/CT). (B) PET/CT scans show the disease burden for 8 patients before treatment (left) and after 4 cycles of R-CHOP (right). NHL-75, with no tumor clonotype detected within the plasma at diagnosis, can be seen to have a large tumor burden. Although no patients had detectable disease at the interim time point, 1 case showed residual disease by PET scan. This patient relapsed 376 days later (NHL-11). Two additional cases showed no disease by PET/CT at the interim time point but went on to relapse 247 (NHL-75) and 267 days (NHL-68) later.