CD30 expression and survival in posttransplant lymphoproliferative disorders

Figures & data

Table 1. Clinicopathological characteristics of PTLD cases by CD30 status.

	N (%) or median (range, min-max)
	All	CD30-positive	CD30-negative	p value
N	50 (100)	35 (70)	15 (30)
PTLD subtype
Polymorphic PTLD	3 (6)	3 (9)	0 (0)
DLBCL	22 (44)	14 (40)	8 (53)
Germinal center	5/21 (24)	0 (0)	5/7 (71)	.001
Non-germinal center	16/21 (76)	14/14 (100)	2/7 (29)
Burkitt lymphoma	2 (4)	0 (0)	2 (13)
Aggressive B-cell lymphoma, unclassifiable	6 (12)	4 (11)	2 (13)
T cell PTLD	12 (24)	9 (26)	3 (20)
ALCL, ALK-negative	4/12 (33)	4 (11)	0 (0)
Other T cell subtype	8/12 (67)	5 (14)	3 (20)
Hodgkin-like PTLD	3 (6)	3 (9)	0 (0)
Lymphoma, unclassifiable	2 (4)	2 (6)	0 (0)
EBER-status of PTLD	49/50 (98)	34	15
EBER+	26 (53)	21 (62)	5 (33)	.07
EBER-	23 (47)	13 (38)	10 (67)
LMP-1-status of PTLD	21/50 (42)	13	8
LMP-1+	12 (57)	9/13 (69)	3/8 (38)	.20
LMP-1-	9 (43)	4/13 (31)	5/8 (63)
Age at PTLD diagnosis, years	53 (0.9-76)	53 (0.9-76)	49 (15–74)
Sex, male	31 (62)	24 (63)	7 (47)	.14
Type of transplant
Kidney ± pancreas	27 (54)	18 (51)	9 (60)
Heart	8 (16)	5 (14)	3 (20)
Liver	7 (14)	6 (17)	1 (6.7)
Lung	8 (16)	6 (17)	2 (13)
Immunosuppressive regimen
Corticosteroids (ever)	50 (100)	35 (100)	15 (100)
Calcineurin inhibitors^a (ever)	48 (96)	33 (94)	15 (100)
Antiproliferative agents^b (ever)	46 (92)	31 (89)	15 (100)
Antithymocyte globulin (ever)	19/48 (40)	14/33 (42)	5 (33)
Time from last SOT to PTLD, years	4.1 (0.18–19.7)	2.1 (0.18–17.8)	8.2 (0.26–19.7)	.01
Localization of PTLD
Nodal, only	10 (20)	9 (26)	1 (7)
Extranodal	40 (80)	26 (74)	14 (93)
Gastrointestinal tract	14 (28)	9 (26)	5 (33)
Allograft	7 (14)	5 (14)	2 (13)
Blood/bone marrow	8 (16)	5 (14)	3 (20)
Liver^c	8 (16)	7 (20)	1 (7)
Central nervous system	3 (6)	0 (0)	3 (20)	.02
Lung^d	7 (14)	3 (9)	4 (27)
Presentation stage (Ann Arbor)	47/50 (94)	34	13
I-III	26/47 (55)	22 (65)	4 (31)	.05
IV	21/47 (45)	12 (35)	9 (69)
Performance status (ECOG)	46/50 (92)	34	12
0–1	29/46 (63)	20 (59)	9 (75)	.49
2–4	17/46 (37)	14 (41)	3 (25)
B symptoms at baseline	47/50 (94)	33	14
Yes	26/47 (55)	20 (61)	6 (43)	.26
No	21/47 (45)	13 (39)	8 (57)
Serum LDH	35/50 (70)	23	12
Normal	9/35 (26)	8 (35)	1 (8)	.12
Elevated	26/35 (74)	15 (65)	11 (92)
Age-adjusted IPI	41/50 (82)	30	11
0–1 point	21/41 (51)	18 (60)	3 (27)	.09
2–3 points	20/41 (49)	12 (40)	8 (73)
PTLD treatment^e	47/50 (94)	34	13
RIS only	5 (11)	4 (12)	1 (8)
Chemotherapy (± RIS)	14 (30)	10 (29)	4 (31)
Rituximab + chemotherapy	5 (11)	3 (9)	2 (15)
Rituximab only	1 (2)	1 (3)	0 (0)
Rituximab + chemotherapy + radiation	2 (4)	0 (0)	2 (15)
Chemotherapy + radiation	4 (9)	4 (12)	0 (0)
Chemotherapy + surgery	7 (9)	4 (12)	3 (23)
Radiation only	1 (2)	1 (3)	0 (0)
Surgery only	4 (9)	3 (9)	1 (8)
Radiation + surgery	1 (2)	1 (3)	0 (0)
None	3 (6)	3 (9)	0 (0)
Treatment response^f	40/44 (91)	27	13
Complete	23/40 (58)	14 (52)	9 (69)
PTLD diagnosis at autopsy	3 (6)	1 (3)	2 (13)
Calendar year of PTLD
1980–1989	2 (4)	2 (6)	0 (0)
1990–1999	24 (48)	19 (54)	5 (33)
2000–2006	24 (48)	14 (40)	10 (67)

^aCyclosporine A or tacrolimus, ^bMycophenolic acid or azathioprine, ^cPTLD in a transplanted liver is reported as allograft and not liver, ^dPTLD in a transplanted lung is reported as allograft and not lung, ^ePTLDs diagnosed at autopsy are excluded, ^fTreatment response on first and secondary treatment, patients who did not receive treatment were excluded.

PTLD: posttransplant lymphoproliferative disorder; DLBCL: diffuse large B-cell lymphoma; ALCL: anaplastic large cell lymphoma; ALK: anaplastic lymphoma kinase; EBER: Epstein-Barr virus-encoded RNA; LMP: Latent Membrane Protein; SOT: solid organ transplantation; ECOG: Eastern Cooperative Oncology Group; LDH: lactate dehydrogenase; IPI: International Prognostic Index; RIS: reduction of immunosuppression.

Figure 1. Immunohistochemical staining of CD30 in PTLD after solid organ transplantation. (A) Polymorphic PTLD with approximately 10% CD30+ cells. (B) Diffuse large B-cell lymphoma, non-germinal center type, with approximately 80% CD30+ tumor cells. (C) Anaplastic large cell lymphoma with 100% CD30+ tumor cells D) Hodgkin lymphoma-like PTLD with 100% CD30+ Hodgkin and Reed/Sternberg (HRS) cells.

Figure 2. Overall survival in PTLD after solid organ transplantation by CD30-status overall (A), in the subgroup of DLBCL (B), and the subgroup of T-cell PTLD (C).

Table 2. Uni- and multivariate analysis of CD30 and overall survival with the use of Cox proportional hazards regression, adjusting for age, sex, and stage according to Ann Arbor.

	Univariate analysis		Multivariate analysis
	All PTLD subtypes (n = 47)		All PTLD subtypes (n = 47)		DLBCL PTLD (n = 22)		T-cell PTLD (n = 12)
Factor	Hazards ratio (95% CI)	p	Hazards ratio (95% CI)	p	Hazards ratio (95% CI)	p	Hazards ratio (95% CI)	p
Age	1.03 (1.00–1.05)	.02	1.03 (1.01–1.06)	.02	1.02 (0.99–1.06)	.19	1.00 (0.91–1.10)	.99
Sex (male)	0.96 (0.49–1.89)	.91	1.05 (0.50–2.22)	.90	0.88 (0.28–2.73)	.82	0.39 (0.06–2.59)	.33
Stage (I-III vs. IV)	0.61 (0.41–0.90)	.01	0.33 (0.16–0.70)	.004	0.48 (0.15–1.53)	.22	4.23 (0.33–54.7)	.27
CD30	1.33 (0.64–2.75)	.44	1.55 (0.68–3.52)	.30	1.61 (0.49–5.28)	.43	2.99 (0.25–35.2)	.38

PTLD: posttransplant lymphoproliferative disorder; DLBCL: diffuse large B-cell lymphoma.

Figure 3. Association between expression of CD30 and FoxP3, a biomarker for regulatory T-cells.