Survival Analysis of Hepatosplenic T Cell Lymphoma: A Population-Based Study Using SEER

Figures & data

Table 1 Baseline Characteristics of Patients with Hepatosplenic T Cell Lymphoma from the SEER database

Characteristics	Original Data Set				P value	Matched-1 Data Set			Matched-2 Data Set
	HSTCL	PTCL-NOS	P value	ALK+ ALCL		HSTCL	PTCL-NOS	P value	HSTCL	ALK+ ALCL	P value
	N=123	N=6794		N= 4017		N= 116	N=116		N=113	N=113
Year of diagnosis, N(%)			0.002		0.006
1975–1995	0(0.0)	496(7.3)		236(5.9)		0	0		0	0
1996–2016	123(100.0)	6298(92.7)		3781(94.1)		116	116		113	113
Median age (range)	40(6–83)	64(0–100)	0.125	54(0–103)	0.011	41 (6–83)	53(10–94)	0.831	43(6–83)	46(11–88)	0.973
Age group, N(%)			<0.001		<0.001			1			1
≤60	100(81.3)	2802(41.2)		2440(60.7)		93(80.2)	93(80.2)		90(79.6)	90(79.6)
>60	23(18.7)	3992(58.8)		1577(39.3)		23(19.8)	23(19.8)		23(20.4)	23(20.4)
Gender, N (%)			0.033		0.084			1
Female	38(30.9)	2744(40.4)		1550(38.6)		36(31.0)	36(31.0)		34(30.1)	34(30.1)	1
Male	85(69.1)	4050(59.6)		2467(61.4)		80(69.0)	80(69.0)		79(69.9)	79(69.9)
Ann-Arbor Stage, N (%)			<0.001		<0.001			1			1
I–II	22(17.9)	2153(31.7)		1784(44.4)		20(17.2)	20(17.2)		19(16.8)	19(16.8)
III–IV	87(70.7)	3548(52.2)		1821(45.3)		84(72.4)	84(72.4)		82(72.6)	82(72.6)
Unknown	14(11.4)	1093(16.1)		412(10.3)		12(10.3)	12(10.3)		12(10.6)	12(10.6)
OSLI, N (%)			<0.001		<0.001			<0.001			<0.001
Nodal	0(0.0)	4549(67.0)		2941(73.2)		0(0.0)	80(69.0)		19(13.5)	89(78.8)
Head and neck	0(0.0)	299(4.3)		89(2.2)		0(0.0)	4(3.4)		0(0.0)	3(2.7)
GI	0(0.0)	305(4.5)		160(4.0)		0(0.0)	7(6.0)		0(0.0)	3(2.7)
CNS	0(0.0)	64(0.9)		38(0.9)		0(0.0)	1(0.9)		0(0.0)	0(0.0)
Liver	2(1.6)	36(0.5)		17(0.4)		1(0.9)	1(0.9)		2(1.8)	0(0.0)
Spleen	121(98.4)	67(1.0)		17(0.4)		115(99.1)	2(1.7)		111(98.2)	0(0.0)
Skin	0(0.0)	957(14.1)		382(9.5)		0(0.0)	7(6.0)		0(0.0)	5(4.4)
Bone marrow	0(0.0)	162(2.4)		12(0.3)		0(0.0)	0(0.0)		0(0.0)	0(0.0)
Others	0(0.0)	329(4.8)		353(8.8)		0(0.0)	14(12.1)		2(1.4)	13(11.5)
Unknown	0(0.0)	26(0.4)		8(0.2)		0(0.0)	0(0.0)		0(0.0)	0(0.0)
Surgery of OSLI, N (%)			<0.001		<0.001			NA			1
No/unknown	118(95.9)	6749(99.3)		3987(99.3)		116(100.0)	116(100.0)		113(100.0)	113(100.0)
Yes	5(4.1)	45(0.7)		30(0.7)		0(0.0)	0(0.0)		0(0.0)	0(0.0)
Radiation alone, N (%)			0. 901		0.048			1			1
No/unknown	107(87.0)	5884(86.6)		3203(79.7)		101(87.1)	101(87.1)		100(88.5)	100(88.5)
Yes	16(13.0)	910(13.4)		814(20.3)		15(12.9)	15(12.9)		13(11.5)	13(11.5)
Chemotherapy alone, N (%)			<0.001		0.004			1			1
No/unknown	21(17.1)	2730(40.2)		1169(29.1)		18(15.5)	18(15.5)		17(15.0)	17(15.0)
Yes	102 (82.9)	4064(59.8)		2848(70.9)		98 (84.5)	98 (84.5)		96(85.0)	96(85.0)

Abbreviations: ALCL, anaplastic large cell lymphoma; ALK, anaplastic lymphoma kinase; OSLI, Organs or systems with lymphoma infiltration; GI, gastrointestinal; CNS, central nervous system; HSTCL, hepatosplenic T cell lymphoma; NA, not available; PTCL-NOS, peripheral T cell lymphoma-not otherwise specified.

Table 2 Clinical Characteristics of Five Chinese Patients with Hepatosplenic T Cell Lymphoma

Characteristics	No of Patients (%)
Age (median, range), year	43 (18–68)
Gender (Male: Female)	4:1
Marital status (Married: Unmarried)	4:1
Advanced Stage	4 (80%)
B symptoms	3 (60%)
BM involvement	4 (80%)
Splenomegaly	5 (100%)
Hepatomegaly	3 (60%)
Lymphadenopathy	0 (0%)
Leukopenia	3 (60%)
Thrombocytopenia	4 (80%)
Anemia	4 (80%)
Elevated TB	3 (60%)
Elevated ALT	3 (60%)
Elevated AST	3 (60%)
Elevated ALP	4 (80%)
Elevated LDH	4 (80%)
Splenectomy	5 (100%)
Radiation alone	0 (0%)
Chemotherapy	5 (100%)
Chemo with anthracycline	2 (40%)
CR/CRu to first line therapy	2 (40%)
PFS (median, range), mos	6.9 (1.3–11.9)
OS (median, range), mos	13.3 (1.5–45.3)

Abbreviations: ALT, alanine aminotransferase; ALP, alkaline phosphatase; AST, aspartate aminotransferase; BM, bone marrow; CR/Cru, complete remission/ unconfirmed complete remission; LDH, lactate dehydrogenase; OS, overall survival; PFS, progression free survival; TB, total bilirubin.

Table 3 The Main Immunophenotypic Features of 5 Chinese Cases with Hepatosplenic T Cell Lymphoma

Marker	Patient 1	Patient 2	Patient 3	Patient 4	Patient 5
CD2	+	NA	NA	NA	+
CD3	+	–	+	+	+
CD5	+	NA	–	–	NA
CD7	+	NA	+	NA	–
CD4	+	NA	–	–	+
CD8	NA	NA	–	–	+
CD79a	NA	NA	–	NA	–
CD56	–	+	+	+	+
CD68	NA	+	–	+	+
CD20	–	–	–	–	–
CD30	–	NA	–	NA	–
GrB	+	NA	+	NA	NA
Pax5	–	–	–	NA	–
ALK	–	NA	–	NA	–
TIA1	+	NA	+	+	+
MPO	+	–	NA	NA	+
TdT	–	NA	NA	–	NA
EBERS	–	–	–	–	–
Ki67	35%+	30%+	80%+	35%+	5%+
TCR expression	NA	NA	NA	TCRγ(+)	NA

Abbreviation: NA, not available.

Table 4 The Staging, Treatment, Outcome, and Survival of 5 Chinese Cases with Hepatosplenic T Cell Lymphoma

	Ann-Arbor Stage	Therapy and Response for Therapy	Outcome	Survival (Months)
Patient 1	IVB	Gem+VP-16+DXM×1, PD; EPOCH+ Chidamide×2, SD; BFM×2, CR	AND	31.6
Patient 2	IB	COP×4, CR; VP-16×2, PD; P-Gemox×6, CR	AND	45.3
Patient 3	IVA	CHOP-B×1, PD; VP-16×1, PD	DOD	1.3
Patient 4	IVA	P-Gemox+Thalidomide×1, PR; Doxorubicin liposome×1, PR; Doxorubicin liposome+ Paclitaxel×1, CR	AND	12.5
Patient 5	IVB	VP-16 PO for 1year, PD	DOD	13.3

Abbreviations: Gem, gemcitabine; VP −16, etoposide; DXM, dexamethasone; PD, progressive disease; EPOCH, etoposide+prednisone+ vincristine+ doxorubicin+ cyclophosphamide; SD, stable disease; BFM, Berlin Frankfurt Munster; CR, complete remission; AND, alive with no evidence of disease; COP, cyclophosphamide+vincristine+ prednisone; P-Gemox, peg-asparaginase+ gemcitabine+oxaliplatin; CHOP-B, cyclophosphamide+ doxorubicin +vincristine+ prednisone+ bleomycin; DOD, died of disease; PR, partial remission.

Figure 1 Overall survival curves of patients with hepatosplenic T cell lymphoma. OS of patients with HSTCL were compared with that in patients with PTCL-NOS among the entire cohort (A) and the same comparison also made between the entire HSTCL cohort and the entire ALK+ ALCL cohort (B). OS of patients with HSTCL were compared with that of patients with PTCL-NOS among the match cohort (C), and OS of patients with HSTCL were compared with that in patients with ALK+ ALCL among the matched cohort (D).

Abbreviations: ALCL, anaplastic large cell lymphoma; ALK, anaplastic lymphoma kinase; HSTCL, hepatosplenic T cell lymphoma; OS, overall survival; PTCL-NOS, peripheral T cell lymphoma-not otherwise specified.

Table 5 Cox Regression Analysis for Survival of Hepatosplenic T Cell Lymphoma Patients

Characteristics	Overall Survival		Lymphoma-Specific Survival
	HR (95% CI)	P value	HR (95% CI)	P value
Age group
≤60	Ref		Ref
>60	1.184(0.592–2.369)	0.632	1.304(0.606–2.806)	0.497
Gender
Female	Ref		Ref
Male	0.860(0.526–1.404)	0.546	0.886(0.508–1.547)	0.671
Race
White	Ref		Ref
Black	1.293(0.644–2.597)	0.470	1.440(0.642–3.232)	0.376
Other	1.704(0.797–3.642)	0.169	1.834(0.772–4.356)	0.170
Marital status
Married	Ref		Ref
Unmarried	2.019(0.688–5.927)	0.201	2.248(0.650–7.771)	0.201
Unknown	1.792(0.617–5.204)	0.283	2.041(0.596–6.994)	0.256
Ann-Arbor Stage
I–II	Ref		Ref
III–IV	0.529(0.177–1.577)	0.253	0.423(0.119–1.501)	0.183
Unknown	0.913(0.351–2.371)	0.851	0.943(0.325–2.739)	0.914
Treatment
No/unknown	Ref
Chemotherapy alone	2.195(0.705–6.830)	0.175	2.089(0.577–7.572)	0.262
Surgery alone	1.978(0.766–5.108)	0.159	2.128(0.737–6.145)	0.163
Surgery + radiotherapy + chemotherapy	48.105(4.659–496.691)	0.001	92.026(7.828–1081.818)	0.000
Radiotherapy + chemotherapy	1.175(0.217–6.378)	0.852	0.826(0.088–7.771)	0.868

Figure 2 Kaplan–Meier survival curves according to the different treatment. Overall survival curves (A) and disease-specific survival curves (B) were made in the patients with primary spleen and liver HSTCL, respectively.

Abbreviation: HSTCL, hepatosplenic T cell lymphoma.

Figure 3 Disease-specific survival curves of patients with hepatosplenic T cell lymphoma. DSS of patients with HSTCL were compared with that in patients with PTCL-NOS among the entire cohort (A) and the same comparison also made between the entire HSTCL cohort and the entire ALK+ ALCL cohort (B). DSS of patients with HSTCL were compared with that of patients with PTCL-NOS among the match cohort (C), and DSS of patients with HSTCL were compared with that in patients with ALK+ ALCL among the matched cohort (D).

Abbreviations: ALCL, anaplastic large cell lymphoma; ALK, anaplastic lymphoma kinase; HSTCL, hepatosplenic T cell lymphoma; DSS, disease-specific survival; PTCL-NOS, peripheral T cell lymphoma-not otherwise specified.