Comparative Study of Post-Transplant Lymphoproliferative Disorders after Solid Organ Transplantation Versus Hematopoietic Stem Cell Transplantation

Introduction.

Post-transplant lymphoproliferative disorder (PTLD) is a well-recognized complication of both solid organ transplantation (SOT) and allogeneic hematopoietic stem cell transplantation (HSCT). However, differences in clinical and biological characteristics between the two procedures are not well established. 

Methods.

We retrospectively evaluated 84 consecutive patients diagnosed of PTLD at a single institution between 1993 and 2014.

Results.

Sixty-three cases occurred after SOT (25 hepatic, 20 renal, 10 cardiac, 9 pulmonary and 1 double-leg transplant) and 21 after HSCT (18 unrelated donor, 16 umbilical cord blood, 2 haploidentical and 2 HLA-identical sibling). There was a male predominance (73% in SOT and 62% in HSCT).  Median age at transplant was 53 years (range, 11-76) in SOT and 43 years (range, 18-59) in HSCT (p=0.03). EBV serostatus before transplant was positive in 78% and 92% for SOT and HSCT recipients, respectively.

Table 1 summarizes clinical and biological characteristics at diagnostic of PTLD. Briefly, HSCT patients had 89% of B symptoms compared to 60% in the SOT group (p<0.001). Waldeyer's ring, spleen and liver involvement was 25%, 45% and 45%, respectively, in the HSCT group; and 5% (p=0.03), 17% (p=0.03) and 13% (p=0.007), respectively, in the SOT group. There was a higher Ann Arbor stage in the HSCT group compare to the SOT group (p<0,05). Time from transplant to PTLD was 4 months (range, 1-27) and 60 months (range, 3-246) for HSCT and SOT group, respectively.

Table 1. Clinical and biological characteristics at diagnostic of PTLD
	SOT	HSCT	p-value
Time from transplant to PTLD (months), median (range)	60 (3 - 246)	4 (1- 27)	<0.0001
Early onset, n (%)	14 (22)	19 (90.5)
Late onset, n (%)	28 (44)	2 (9.5)
Very late onset, n (%)	20 (32)	0 (0)
B symptoms, n (%)	33 (60)	16 (89)	<0.001
Nodal involvement, n (%)	33 (59)	12 (67)	0.75
Waldeyer's ring	3 (5)	5 (25)	0.03
Spleen	10 (17)	9 (45)	0.03
Extranodal involvement, n (%)	35 (58)	16 (80)	0.1
Bone marrow	8 (14)	6 (30)	0.2
Central nervous system	4 (7)	5 (25)	0.07
Liver	8 (13)	9 (45)	0.007
Gastrointestinal	13 (22)	2 (10)	0,4
Lung	7 (12)	1 (5)	0,7
Kidney	6 (10)	1 (5)	0,8
LDH (U/L), median (range)	568 (201 - 2415)	702 (328 - 1515)	0.24
ECOG			1
0-1	41 (87)	8 (89)
2-4	6 (13)	1 (11)
Ann Arbor stage			<0.05
I	12 (21.4)	1 (4.8)
II	8 (14.3)	3 (14.3)
III	8 (14.3)	0 (0)
IV	28 (50.0)	17 (81.0)
WHO classification, n (%)			0.2
Early lesion	0 (0)	0 (0)
Polymorphic	7 (12.3)	4 (20)
Monomorphic B	45 (79)	16 (80)
DLBCL	36 (63.2)	16 (80)
Others	9 (15.8)	0 (0)
Monomorphic T/NK	3 (5.3)	(0)
Monomorphic E. Hodgkin	2 (3.5)	(0)
ND	6 (9.5)	1 (5)
CD20+, n (%)	42 (86)	13 (68)	0.2

Most patients (95%) had received calcineurine inhibitors with other immunosuppressive agents. PTLD treatment was different between both groups (p=0.0001); in the SOT group, 22% received rituximab as monotherapy and 63% chemotherapy, as compared with 62% and 19% in the HSCT group, respectively. In SOT, 42 (70%) patients died at a median of 208 days (range, 0-4178) while in HSCT 19 (91%) patients died at a median of 26 days (range, 0-485) (p=0.002). Overall survival at 4 years was 35% for SOT and 7% for HSCT (p<0.0001). Most deaths were directly related to PTLD.

Conclusions.

PTLD after HSCT appears to be a different entity because of the earlier appearance after transplant, a more aggressive clinical presentation (B symptoms, nodal and extranodal involvement, higher Ann Arbor staging system) and a poorer survival outcome compared with PTLD after SOT.