Abstract:

The Posttrasplant Lymphoproliferative Disease (PTLD) is a group of

disorders that includes uncontrolled plasmatic or lymphoid
proliferations, associated with the use of immunosuppression and the
Epstein-Barr Virus(EBV) infection. In the posttrasplant patients it
represents one of the most serious and potentially fatal complications.
The main risk factors are: pediatric receptors, intensity of
immunosuppression, type of transplant and EBV negative serostatus. Up
to 15% of the pediatric Liver Transplant(LT) receptors develop PTLD
with mortality rates between 40-70%.
We conducted a cohort, retrospective, comparative study that included
all LT recipients from a single center from May 1998-July 2015, with
graft survival greater than one month. Patients were divided into two
groups according to the type of Epstein Barr viral load monitoring.
Group I (1998-2007): PCR was not available or it was only qualitative
with limited access. Group II (2008-2015): Serial quantitative PCR in
plasma and leukocytes(in the postransplant period: every 15 days
during the first 6 months, then one time per month for the next 6
months and finally every 3-6 months) with aggressive tapering of
immunosuppression as soon as viral replication was detected. The
analized variables were: age at the moment of the transplant, recipients
in each group with age < 4 years, diagnose, EBV serostatus previous to
the transplant, reject episodes, incidence of PLTD and survival rates of
the patient. SPSS for the stadistic bivarated analysis was used. Fisher’s
exact test for categoric variables was used, Students-T test with
continuous variables and survival rates with Kaplan Meier and Log-
Rank.
Results: A total of 98 receptors were included, 41 (41.8%) were EBV-
seronegative before LT. EBV-replication was confirmed in 74 patients
(75.5%) during posttransplant follow-up, being more frequent in the
seronegative (primoinfection 87.8%) than in seropositive patients
(reactivation 66.6%). In eight receptors(8.1%) PLTD was developed in
average at 14.3 months post transplant(8-26 months), 7/8 were <3
years at the transplant, 4/8 were D+/R- for EBV and all of them had EBV
replication postransplant confirmed with PCR.
The patients diagnose were 4 Biliary atresia, 3 tyrosinemia and 1
familial hypercholesterolemia. PTLD was in 4 patients Lymphoma(2
Burkitt, 1 B-cell, 1 T-cell) 2 polyclonal polymorphic plasmocytoid and 1
lymphoid hyperplasia. Five patients with PLTD died (2 due to
complications with chemotherapy, 2 due to chronical reject of the graf
and 1 sepsis) 3 cleared the PTLD after diminishing or suspending the
immunosupresion(1 is nowadays tolerant). Analyzing both groups
there were no significative differences in the initial diagnose, age at the
transplant(5.6 vs 7.3 years, p=0.069), total of patients <4 years (53.2%
vs 35,3%, p=0.103) or seronegative status for the EBV (44.7% vs 37.3%,
p=0.54); however the incidence of the PTLD deacreased with statistical
significance 14.9% to 1.9% (p=0.026), and so did the frequency of graft
rejection 51.1% vs 29.4%, p=0.039.
Results: The survival rates of the patient at the first year and 5 years
were 94.7% and 85%, with no statistical significance between both
groups (93.6% vs 95.% y 83% vs 91.1%, respectively, p=0.427).
Conclusion: Our results show that the strict molecular screening of the
EBV replication with cuantitative PCR and an aggressive reduction of
the immunosuppression manage to reduce dramatically the incidence of
PTLD (14.9% vs 1.9%), without meaning a greater incidence of graft
rejection, that in fact also dimished with statistical significance. We
suggest that this strategy should be used in the follow up from all the
pediatric LT recipients.