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Table 2 Clinical application of CTCs in T cell lymphoma

From: Liquid biopsy in T-cell lymphoma: biomarker detection techniques and clinical application

Lymphoma subtypes

Author

PMID/doi

Biomarker

Liquid Biopsy

Method

No. of patients

Results

Clinical applications

CTCL, PTCL, NOS, T-LBL, nTFHL-AI

Assaf, C et al. [79]

10887129

CTCs

PB

PCR, TCR-beta

62

TCR-gamma PCR revealed an approximate 20% lower detection rate in the same set of samples than with the TCR-beta PCR method

diagnostic

PTCL, NOS, nTFHL-AI, ALCL, ENKTL

Pu Q et al. [80]

36466894

CTCs

PB

FC, 15 markers

81

NTFHL-AI: PD-1 + % > 38.01, CD10 + % > 7.46

ENKTL-N: CD56

ALCL: CD30 and HLA-DR

P MRD sensitivity, 85.71%

prognostic:

NTFHL-AI, CD7, CD38, Ki-67

PTCL, NOS, CD3, CD8

ENKTL, CD56 and HLA-DR

diagnostic, prognosis,

ALK-positive ALCL

Damm-Welk, Christine et al. [81]

17392503

CTCs

PB

RT-PCR,

RQ-PCR,

NPM::ALK expression

80

NPM::ALK: 47.5%

CI-Rs:

38 pts PCR-positive, 50% ± 10% vs 42 pts PCR-negative, 15% ± 7% (P < 0.001)

CI-R:

16 pts NPM::ALK > 10 NCNs, 71% ± 14% vs 59pts ≤ 10 NCNs, 18% ± 6% (P < 0.001)

prognosis

ALK-positive ALCL

Damm-Welk, Christine et al. [82]

31649129

CTCs

PB

dPCR,

RQ-PCR

NPM::ALK

91

Applying a cut-off of 30 copies NPM::ALK/104 copies ABL1 for quantification by dPCR, almost identical groups of patients were separated as those separated by RQ-PCR

prognosis

ALCL

Mussolin, Lara et al. [83]

32987765

CTCs

PB

qualitative PCR, NPM::ALK

420

high-risk group (bpHR): MDD-positive & SC/LH pattern; 10-year PFS 40%

low-risk group (bpLR): MDD-negative & without SC/LH pattern; 10-year PFS 86%

intermediate-risk group (bpIR): remaining patients. 10-year PFS 75%

(P < 0.0001)

prognosis

T-LBL

Coustan-Smith E et al. [84]

19546402

CTCs

PB

FC

99

Two-year EFS:

patients ≥ 1% T-LL cells in bone marrow vs < 1% vs ≥ 5%, 68.1% ± 11.1% (SE) vs 90.7% ± 4.4%(P = .031) vs 51.9% ± 18.0% (P = .009)

diagnostic Prognosis

longitudinal monitoring

PTCL, NOS, ALK-negative ALCL, nTFHL-AI

Gauthier, J et al. [85]

27775693

CTCs

PB

mpFC, 10-colour

FC, TCR V-beta,

29

7/29 patients were MDD + .pre-ASCT MDD + OS(19% vs 89%, P < 0.001), CIR, 85% vs 36%, P < 0.001)

prognosis

ALK-positive ALCL

Kalinova M et al. [86]

17320171

CTCs

PB

RQ-RT-PCR, NPM::ALK

10

RQ-RT-PCR revealed NPM::ALK positivity 100% from relapses and/or closely before a relapse in at least one of the iliac BM trephines

MRD

ALK-positive ALCL

Damm-Welk, Christine et al. [87]

24297868

CTCs

PB

RT-PCR, NPM::ALK

180

MDD + : 103/180. MRD + :52(before the second therapy course in 52 MDD + pts)

CIR: 26 MDD + /MRD + pts (81% ± 8%) vs 26 pts MDD + /MRD- (31% ± 9%) vs 77 pts MDD- (15% ± 5%) (P < 0.001)

Five-year survival: MDD- vs MDD + /MRD- vs MDD + /MRD + pts: 91% ± 3% vs 92% ± 5% vs 65% ± 9% (P < 0.001)

MRD

ALK-positive ALCL

Rigaud, Charlotte et al. [88]

33687135

CTCs

PB

multiplex RT-PCR, NPM1::ALK

138

diagnosis: 87/138 pts MDD + 

Early MRD (before the second course (BM1)) + : 18/33, MRD-:15/33

Three-year PFS:81.1% in MDD − , 69.6% in MDD + /MRD − , 15.2% in MDD + /MRD + pts

MRD

ALK-positive ALCL

Pokorna P et al. [89]

35700412

CTCs

PB

RT-PCR, NPM1::ALK

1

intermittent dosing of lorlatinib improved treatment response and prolongation of the child’s EFS. MRD dynamics supported the selected administration schedule

MRD

CTCL

Wolfe, J T et al. [90]

7602365

CTCs

PB

PCR, T-cell receptor-beta (TCR-beta) rearrangements

1

a complete clinical response CTCL patient detected MRD

when clinical relapsed identified a common clonal origin for CTCL and LCT

MRD

ATLL, CTCL, T-LGLL, PTCL, NOS

Tembhare P et al. [91]

22261447

CTCs

CSF, FNA

FCM, TCR-V(β)-R

8

6 CSF FCM + , 1 was positive by cytomorphologic evaluation, 3 were negative, 2 were suspicious or atypical

All FNA specimens were FCM + . 4/8 were positive by cytomorphologic evaluation and four were suspicious or atypical

MRD

ATLL

Shao, Haipeng et al. [92]

20231613

CTCs

PB

FC, 25 marker

PCR: TRG Gene Rearrangements and HTLV-1

17

FC: 0.29% ATLL cells/WBC (4.9 cells/microL)

PCR: TRG gene rearrangement, 74% demonstrated. 14% suspicious;

HTLV-1,96%

MRD:

FC & PCR: 30/50, 60%

MRD

ATLL, T-LGLL, PTCL, NOS, T-PLL

Tembhare, Prashant et al.[93]

21571962

CTCs

PB

FC, TCR-Vβ

41

TCR-V(β)-R analysis is a sensitive method for detection of MRD (14/14,100%)

diagnostic MRD

T-ALL

Wu, David et al. [94]

22593176

CTCs

PB

mpFC, 18 marker

HTS, TCRG and TCRB CDR3

43

diagnosis:

TCRB-HTS: 31/43,

TCRG-HTS: 27/43

MRD:

TCRB-HTS & CRG-HTS: 25/35

mpFC: 13/35

MRD

MF

SS

Weng, Wen-Kai et al. [95]

24307695

CTCs

PB

mpFC, 7-marker, TCRβ

HTS, TCRβ

10

malignant clones were detected by TCRB-HTS in all ten cases, four of these patients achieved molecular clearance in skin after transplant

MRD

  1. CTCs circulating tumor cells, MRD Minimal residual disease, ATLL adult T-cell leukemia/lymphoma, T-LGLL T-large granular lymphocytic leukaemia. T-PLL, T-prolymphocytic leukemia, ALCL Anaplastic large cell lymphoma, nTFHL-AI Nodal T-follicular helper cell lymphoma, angioimmunoblastic-type, PTCL, NOS peripheral T-cell lymphoma, not otherwise specified, T-LBL T-cell lymphoblastic lymphoma, T-ALL T-cell lymphoblastic leukemia, CTCL cutaneous T-cell lymphoma, ENKTL extranodal NK/T-cell lymphoma, NGS Next-generation sequencing, GE genome equivalent, WES Whole-exome sequencing, HTS high-throughput sequencing, AS-PCR Allele-specific polymerase chain reaction, RQ-PCR Real-time quantitative PCR, dPCR digital polymerase chain reaction, CS-PCR clonal specific PCR, TCR T-cell receptor, SC/LH small cell/lymphohistiocytic, LCT large-cell transformation, CI-Rs cumulative incidence of relapses, PB peripheral blood, MF Mycosis fungoides, SS Sézary syndrome, CSF cerebrospinal fluid, MDD Minimal disseminated disease, FNA fine-needle aspirate, MFC multicolor flow cytometric, mpFC Multiparameter flow cytometry, OS overall survival, DFS disease-free survival. PFS progression-free survival, BM bone marrow