Pre-treatment [¹⁸F]FDG PET/CT for assessing bone marrow involvement and prognosis in patients with newly diagnosed peripheral T-cell lymphoma

Figures & data

Figure 1. A flowchart of patient selection, diagnostic performance, and survival analysis. Abbreviations: PTCL, peripheral T-cell lymphoma; PET/CT, positron emission tomography/computed tomography; SUV, standardized uptake value; PTCL-NOS, peripheral T-cell lymphoma, not otherwise specified; AITL, angioimmunoblastic T-cell lymphoma; PTCL-TFH, nodal T-follicular helper (TFH) cell lymphoma; ALCL, anaplastic large cell lymphoma; HSTCL, hepatosplenic T-cell lymphoma; MEITCL, monomorphic epitheliotropic intestinal T-cell lymphoma.

Table 1. Baseline characteristics in all PTCL patients.

Characteristic	Total	PET (-) (n = 170)	PET (+) (n = 31)	P-value
Male, no. (%)	114/201	95 (56.2)	19 (59.4)	0.846
Age >60 years, no. (%)	120/201	102 (60.4)	18 (56.3)	0.697
Stage III/IV, no. (%)	176/201	144 (85.2)	32 (100)	0.017
ENSs ≥2, no. (%)	12/201	9 (5.3)	3 (9.4)	0.411
B symptom, no. (%)	80/201	69 (40.8)	11 (34.4)	0.558
ECOG PS ≥2, no. (%)	49/201	43 (25.4)	6 (18.8)	0.506
LDH >250U/L, no. (%)	109/196	91 (55.5)	18 (56.3)	1.000
B2M > 2.53ug/L, no. (%)	100/135	81 (73.0)	19 (79.2)	0.616
WBC (median ± SD, 10^9 /L)	n = 200	n = 168	n = 32	0.510
		8.05 ± 6.18	7.28 ± 5.64
HB (median ± SD, g/L)	n = 200	n = 168	n = 32	0.038
		113.30 ± 25.02	103.13 ± 26.78
PLT (median ± SD, 10^9 /L)	n = 200	n = 168	n = 32	0.299
		196.30 ± 107.18	174.84 ± 104.30
Albumin (median ± SD, g/L)	n = 199	n = 167	n = 32	0.311
		37.78 ± 7.13	36.38 ± 6.92
CRP (median ± SD, mg/L)	n = 189	n = 157	n = 32	0.006
		18.07 ± 26.34	33.12 ± 35.68
High level of M/L, no. (%)	32/201	7 (21.9)	25 (78.1)	<0.001
BMB (+), no. (%)	37/201	21 (12.4)	16 (50.0)	<0.001
EBER positive, no. (%)	32/182	28 (18.5)	4 (12.9)	0.607
IPI, no. (%)	n = 196	n = 164	n = 32	0.195
0–1	41/196	38 (23.2)	3 (9.4)
2	71/196	55 (33.5)	16 (50.0)
3	60/196	50 (30.5)	10 (31.3)
4–5	24/196	21 (12.8)	3 (9.4)
PIT, no. (%)	n = 196	n = 164	n = 32	0.850
0	26/196	22 (13.4)	4 (12.5)
1	66/196	55 (33.5)	11 (34.4)
2	70/196	57 (34.8)	13 (40.6)
3–4	34/196	30 (18.3)	4 (12.5)
First-line treatment, no. (%)	n = 195	n = 164	n = 31	0.626
CHOP or COP	82/195	72 (43.9)	10 (32.3)
CHOPE	51/195	42 (25.6)	9 (29.0)
CHOP + AZA	27/195	21 (12.8)	6 (19.4)
Combined with brentuximab vedotin	14/195	10 (6.1)	4 (12.9)
Combined with lenalidomide	4/195	3 (1.8)	1 (3.2)
Combined with chidamide	6/195	6 (3.7)	0 (0.0)
Others	11/195	10 (6.1)	1 (3.2)
Transplantation, no. (%)	19/201	16 (9.5)	3 (9.4)	0.987
Subgroup, no. (%)	n = 201	n = 169	n = 32	0.942
PTCL-NOS	39/201	33 (19.5)	6 (18.8)
AITL	108/201	90 (53.3)	18 (56.3)
ALCL	29/201	24 (14.2)	5 (15.6)
PTCL-TFH	13/201	11 (6.5)	2 (6.3)
MEITCL	6/201	6 (3.6)	0 (0)
HSTCL	6/201	5 (3.0)	1 (3.1)

Abbreviations: PTCL, peripheral T-cell lymphoma; PET (+), bone marrow involvement confirmed by PET/CT; PET (-), no bone marrow involvement confirmed by PET/CT; ENSs, extranodal sites; ECOG PS, Eastern Cooperative Oncology Group performance status; LDH, lactate dehydrogenase; B2M, Beta2-microglobulin; WBC, white blood cell; SD, standard deviation; HB, hemoglobin; PLT, platelet count; CRP, C-reactive protein; M/L, the highest SUV of BM divided by the mean SUV of the liver; BMB (+), bone marrow infiltration comfiremd by biopsy; EBER, EBV-encoded RNA; IPI, International Prognostic Index; PIT, prognostic index for PTCL; CHOP, cyclophosphamide, doxorubicin, vincristine, and prednisone; COP, cyclophosphamide, vincristine, and prednisone; CHOPE, etoposide plus CHOP; AZA, azacytidine; PTCL-NOS, peripheral T-cell lymphoma, not otherwise specified; AITL, angioimmunoblastic T-cell lymphoma; PTCL-TFH, nodal T-follicular helper (TFH) cell lymphoma; ALCL, anaplastic large cell lymphoma; HSTCL, hepatosplenic T-cell lymphoma; MEITCL, monomorphic epitheliotropic intestinal T-cell lymphoma.

Table 2. Diagnostic performance in all PTCL patients.

PTCL		BMB		kappa
		(+)	(-)
PET/CT	(+)	16	16	κ = 0.353
	(-)	21	148
Sensitivity = 43.2% Specificity = 90.2%

Abbreviations: PTCL, peripheral T-cell lymphoma; PET/CT, positron emission tomography/computed tomography; BMB, bone marrow biopsy.

Figure 2. OS and PFS in patients with PTCL according to PET status (2A and 2B), BMB finding (2C and 2D) and level of M/L (2E and 2F). Abbreviations: OS, overall survival; PFS, progression-free survival; PTCL, peripheral T-cell lymphoma; PET (+), bone marrow involvement confirmed by PET/CT; PET (-), no bone marrow involvement confirmed by PET/CT; BMB (+), bone marrow involvement confirmed by biopsy; BMB (-), no bone marrow involvement confirmed by biopsy; M/L, the highest SUV of BM divided by the mean SUV of the liver.

Table 3. Univariate and multivariate statistical analysis of prognostic factors for OS and PFS in PTCL Patients.

Prognostic factors	OS			PFS
	Univariate analysis	Multivariate analysis		Univariate analysis	Multivariate analysis
		HR (95%CI)	P-value		HR (95%CI)	P-value
Age	0.042			0.018
Symptom	0.060			0.302
BMB (+)	0.023			0.712
LDH	0.027			0.004
ECOG PS	<0.001	3.501 (2.083-5.884)	<0.001	<0.001	2.340 (1.543-3.547)	<0.001
HB	<0.001			<0.001
PLT	0.005			0.002
Albumin	<0.001	0.955 (0.915-0.996)	0.033	0.002	0.963 (0.934-30.992)	0.015
M/L	<0.001	1.825 (1.071-3.110)	0.027	0.002
Transplantation	0.054			0.073

Notes: *Some parts are blank because the data is not statistically significant in multivariate analysis.

Abbreviations: OS, overall survival; PFS, progression-free survival; HR, hazard ratio; CI, confidence interval; BMB (+), bone marrow involvement confirmed by biopsy; LDH, lactate dehydrogenase; ECOG PS, Eastern Cooperative Oncology Group performance status; HB, hemoglobin; PLT, platelet count; M/L, the highest SUV of BM divided by the mean SUV of the liver.

Table 4. Relative retrospective studies about the diagnostic value of PET/CT for the identification of the involvement of bone marrow.

Investigation (year)	Total number	No. of patients BMB+	No. of patients PET+	Sensitivity	Specificity	PPV	NPV	complement
Sundaram et al. (2020) [2]	53 PTCL + 7 NKTCL	15	8	53.3% (95% CI 29.4, 76.1)	100% (95% CI 94.6, 100)	100% (95% CI 73.8, 100)	86.5% (95% CI 75.4, 93.8)
Abe et al. (2019) [14]	83 PTCL	28	25	89.3%	100%	100%	94.8%	BMB (+): BMB specimens positive for PTCL or the lack of an initially abnormal bone marrow uptake on follow-up PET/CT indicative of a successful treatment response.
Koh et al. (2019) [16]	63 PTCL + 46 NKTCL	39	41	61.5%	75.7%	N/A	N/A	PET (+): moderately increased diffuse uptake that is higher than the liver uptake; markedly increased diffuse uptake and multifocal uptakes in the bone marrow
Pham et al. (2017) [35]	16 PTCL	16	N/A	50%	N/A	N/A	N/A
El-Galaly et al. (2015) [15]	125 PTCL	17	13	18% (95% CI 4–43)	90% (95% CI 82–95)	N/A	N/A

Abbreviations: PTCL: peripheral T-cell lymphoma; NKTCL: natural killer/T cell lymphoma; PET/CT: positron emission tomography/computed tomography; BMB+: bone marrow involvement by bone marrow biopsy; PET+: bone marrow involvement by PET/CT; PPV: positive predictive value; NPV: negative predictive value; BMB: bone marrow biopsy; CI: confidence interval; N/A: not applicable.

Sundaram S, et al. Utility of bone marrow aspirate and biopsy in staging of patients with T-cell lymphoma in the PET-Era - tissue remains the issue. Leuk Lymphoma. 2020;61:3226–3233. doi:10.1080/10428194.2020.1798950

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