194

Practical Urology: EssEntial PrinciPlEs and PracticE

posttransplant. The allograft vessels are most

is a relatively uncommon complication of both

often involved and not the parenchyma.Therapy

solid organ and bone marrow transplantation.

is not often helpful secondary to the antibody

Most cases of PTLD are associated with an

mechanism and most of the drugs are directed

Epstein-Barr virus (EBV) infection. This occurs

toward T-cells.However,IVIG and plasmaphere-

as a consequence of reactivation of the recipi-

sis may play a role.

ent’s virus after transplantation or from a donor-

Acute rejection is T-cell-mediated. These types

acquired

primary

posttransplantation EBV

of rejections are more common, and their onset

infection. T-cell lymphoproliferative disorders

can be weeks to months to years. Lymphocytes

not associated with EBV infection have also

and macrophages infiltrate the allograft. Damage

been documented, yet the vast majority are

ensues to the parenchyma, and scarring damages

B-cell proliferations.17

the structural integrity of the organ. The initial

Most cases of PTLD are observed in the first

hint that a rejection episode has begun is usually

year following transplant. Higher levels of

organ dysfunction, fever, malaise, or allograft

immunosuppressive

regimens are associated

tenderness.Thedifferentialdiagnosismustalways

with a higher incidence of PTLD. Successful

include rejection; however, the patient’s presen-

treatment of PTLD involves the reduction or

tation is most often not easily discernible. A

withdrawal of immunosuppressive medications.

biopsy of the organ can confirm or dismiss the

Unfortunately, this approach risks significant

diagnosis. Fortunately, therapies are usually suc-

allograft rejection and possible allograft loss.

cessful in reversing this type of rejection if treated

Other treatment modalities that have been dem-

promptly.The treatments often include the use of

onstrated as effective include surgical excision

large pulse doses of steroids and/or antilympho-

of the lesion, radiation therapy, chemotherapy,

cyte antibody preparations as described above.

monoclonal antibodies, and interferon.

The successful treatment of rejection is often

PTLD is an uncommon phenomenon; how-

accompanied with the adjustment of the patient’s

ever, it has been described in all types of solid

maintenance immunosuppression.

and bone marrow transplants. Up to 60% of

Chronic allograft rejection appears to affect

patients with renal allografts who develop PTLD

nearly every transplanted organ. Most often it

do so within 6 months of their transplant.

occurs over the lifetime of a transplanted organ

Cardiac transplant patients had an incidence

at clinically undetectable levels. Its etiology is

ranging from 5% to13% with half developing

unknown; however, its incidence is increased in

PTLD within 6 months of transplantation. In

those patients who have experienced previous

liver transplantation, the incidence is 2% with

acute rejection episodes. Its onset is months to

most developing PTLD within 1 year of trans-

years following the transplant. The appearance

plantation.17 Renal allograft patients had an

on organ biopsy presents as persistent perivascu-

overall incidence of PTLD of approximately 2%;

lar and interstitial inflammation. There is little to

however, it was slightly higher in the pediatric

no lymphocyte involvement.Tailoring the immu-

population (1–10%).18,19

nosuppression regimen aims to prevent persis-

tent rejection while attempting to minimize the

Summary

side effects of the drugs on the allograft. This

strategy occasionally will extend graft survival;

however, the results are not overly encouraging.

Overall,

immunosuppression has transformed

Unfortunately, the only definitive remedy for this

the field of transplantation. Unfortunately with

type of rejection remains re-transplantation.

great advances, confounding factors are often

encountered. Immunosuppression is a powerful

Posttransplant

tool in combating rejection; however, the under-

lying auspices of infection must not be allowed to

Lymphoproliferative Disease

prevail.Initially,induction therapy prevents early

rejection and allows for the titration of mainte-

nance therapy.Maintenance therapy is frequently

Posttransplant lymphoproliferative disease

adjusted for the life of the allograft to accommo-

(PTLD) is the other spectrum of chronically

date physiologic changes in the recipient. The

immunosuppressed transplant patients. PTLD

ultimate goal remains the prevention of rejection

and avoidance of over-immunosuppression and

9.

von Andrian UH, Mackay CR. T-cell function and migra-

opportunistic infections. The use of combined

tion: two sides of the same coin. N Engl J Med. 2003;

therapies allows for lower doses and minimiza-

343:1020

10.

Genestier L, Fournel S, Flacher M, Assossou O, Revillard

tion of potential side effects as well as a multifac-

JP, Bonnefoy-Berard N. Blood. 1998;91:2360

eted approach to suppress the innate immune

11.

Préville X, Flacher M, LeMauff B, et al. Mechanisms

response.

involved in antithymocyte globulin immunosuppressive

activity in a nonhuman primate model. Transplantation.

2001;71:460

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