Table 1.

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

Diagnosis	Precancerous condition	Diagnosis/pretreatment	During therapy	Posttreatment/surveillance	Relapse/progression
ALL		CTC or malignant BM cell: levels predict outcome before allo-SCT38,41,43,55		CTC or malignant BM cell: positivity predicts clinical outcome29-35,38-43,54,55; positivity predicts relapse39,56; positivity might guide treatment decisions33,35	Malignant BM cell: positivity identifies relapse39
HL				ctDNA: positivity tends to predict clinical outcome66,68
MM		CTC or malignant BM cell: genotyping defines clinical risk (eg, t(4:14))71Autograft: positivity predicts clinical outcome82		Malignant BM cell: positivity predicts clinical outcome72,73,77-79; positivity pre-lenalidomide maintenance predicts clinical outcome78
MCL		CTC or malignant BM cell: positivity before auto-SCT predicts survival87		CTC or malignant BM cell: positivity predicts clinical outcome85,86,88; detection might guide treatment decisions84
CLL		CTC: genotyping defines clinical risk (eg, del(17p13), TP53)92,93; assessment might identify therapeutic targets (eg, del(17p13))92,93		CTC or malignant BM cell: levels predict clinical outcome68,94-99,103,104; dynamics predict relapse97
FL	Healthy PBMC: BCL2-IGH rearrangement levels >0.01% are associated with a 23-fold higher risk for malignant transformation112	ctDNA or malignant BM cells: levels correlate with clinical outcome122,132		CTC or malignant BM cells: positivity predicts clinical outcome116-120,125,127,129,131	CTC: positivity identifies relapse116
DLBCL		ctDNA: levels correlate with tumor burden and PFS22,134,135; genotyping identifies COO subtypes22; profiling identifies DH and TH lymphomas22	ctDNA: profiling identifies resistant clones22,137; negativity after 2 cycles predicts PFS134	CTC or ctDNA: predicts relapse with 3-6 month lead time22,134,135; positivity predicts clinical outcome22,134	CTC 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.