Table 1. Clinical impact of noninvasive... | American Society of Hematology

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-SCT^38,41,43,55		CTC or malignant BM cell: positivity predicts clinical outcome^{29-35,38-43,54,55}; positivity predicts relapse^39,56; positivity might guide treatment decisions^33,35	Malignant BM cell: positivity identifies relapse³⁹
HL				ctDNA: positivity tends to predict clinical outcome^66,68
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 outcome^72,73,77-79; 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 outcome^85,86,88; 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 outcome^{68,94-99,103,104}; 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 outcome^122,132		CTC or malignant BM cells: positivity predicts clinical outcome^{116-120,125,127,129,131}	CTC: positivity identifies relapse¹¹⁶
DLBCL		ctDNA: levels correlate with tumor burden and PFS^22,134,135; genotyping identifies COO subtypes²²; profiling identifies DH and TH lymphomas²²	ctDNA: profiling identifies resistant clones^22,137; negativity after 2 cycles predicts PFS¹³⁴	CTC or ctDNA: predicts relapse with 3-6 month lead time^22,134,135; positivity predicts clinical outcome^22,134	CTC or ctDNA: positivity identifies relapse^{22,134,135,137}; profiling detects histological transformation²²

Diagnosis	Precancerous condition	Diagnosis/pretreatment	During therapy	Posttreatment/surveillance	Relapse/progression
ALL		CTC or malignant BM cell: levels predict outcome before allo-SCT^38,41,43,55		CTC or malignant BM cell: positivity predicts clinical outcome^{29-35,38-43,54,55}; positivity predicts relapse^39,56; positivity might guide treatment decisions^33,35	Malignant BM cell: positivity identifies relapse³⁹
HL				ctDNA: positivity tends to predict clinical outcome^66,68
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 outcome^72,73,77-79; 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 outcome^85,86,88; 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 outcome^{68,94-99,103,104}; 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 outcome^122,132		CTC or malignant BM cells: positivity predicts clinical outcome^{116-120,125,127,129,131}	CTC: positivity identifies relapse¹¹⁶
DLBCL		ctDNA: levels correlate with tumor burden and PFS^22,134,135; genotyping identifies COO subtypes²²; profiling identifies DH and TH lymphomas²²	ctDNA: profiling identifies resistant clones^22,137; negativity after 2 cycles predicts PFS¹³⁴	CTC or ctDNA: predicts relapse with 3-6 month lead time^22,134,135; positivity predicts clinical outcome^22,134	CTC or ctDNA: positivity identifies relapse^{22,134,135,137}; 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.

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