Table 1.

Clinical impact of noninvasive disease detection at distinct disease milestones in lymphoid malignancies

DiagnosisPrecancerous conditionDiagnosis/pretreatmentDuring therapyPosttreatment/surveillanceRelapse/progression
ALLCTC or malignant BM cell: levels predict outcome before allo-SCT38,41,43,55CTC or malignant BM cell: positivity predicts clinical outcome29-35,38-43,54,55; positivity predicts relapse39,56; positivity might guide treatment decisions33,35Malignant BM cell: positivity identifies relapse39
HLctDNA: positivity tends to predict clinical outcome66,68
MMCTC or malignant BM cell: genotyping defines clinical risk (eg, t(4:14))71Autograft: positivity predicts clinical outcome82Malignant BM cell: positivity predicts clinical outcome72,73,77-79; positivity pre-lenalidomide maintenance predicts clinical outcome78
MCLCTC or malignant BM cell: positivity before auto-SCT predicts survival87CTC or malignant BM cell: positivity predicts clinical outcome85,86,88; detection might guide treatment decisions84
CLLCTC: genotyping defines clinical risk (eg, del(17p13), TP53)92,93; assessment might identify therapeutic targets (eg, del(17p13))92,93CTC or malignant BM cell: levels predict clinical outcome68,94-99,103,104; dynamics predict relapse97
FLHealthy PBMC: BCL2-IGH rearrangement levels >0.01% are associated with a 23-fold higher risk for malignant transformation112ctDNA or malignant BM cells: levels correlate with clinical outcome122,132CTC or malignant BM cells: positivity predicts clinical outcome116-120,125,127,129,131CTC: positivity identifies relapse116
DLBCLctDNA: levels correlate with tumor burden and PFS22,134,135; genotyping identifies COO subtypes22; profiling identifies DH and TH lymphomas22ctDNA: profiling identifies resistant clones22,137; negativity after 2 cycles predicts PFS134CTC or ctDNA: predicts relapse with 3-6 month lead time22,134,135; positivity predicts clinical outcome22,134CTC or ctDNA: positivity identifies relapse22,134,135,137; profiling detects histological transformation22
  • Role of PBMC, CTC, ctDNA, and BM cell profiling for detection of premalignant states in healthy individuals, identification of clinically relevant biomarkers, and prediction of outcome in lymphoid malignancies at distinct disease milestones.

  • COO, cell of origin; DH, double hit; DLBCL, diffuse large B-cell lymphoma; TH, triple hit.