Lymphoproliferative disorders and de novo malignancies in intestinal and multivisceral recipients: improved outcomes with new outlooks.
BACKGROUND
Early experience with intestinal and multivisceral transplantation was plagued with high risk of rejection and posttransplant lymphoproliferative disorders (PTLD). To improve outcome, innovative management and immunosuppressant strategies were sequentially evolved.


METHODS
With initiation of the program in 1990, serial monitoring of Epstein-Barr-Viral load was introduced in 1994 with adoption of preemptive antiviral therapy. In 1995, cyclophosphamide or daclizumab induction was added to the tacrolimus-steroid-based multiple drug immunosuppressions. Such a conventional approach was replaced in 2001 with a novel immunosuppressive protocol consisting of recipient pretreatment with a single dose of rabbit antithymocyte globulin or alemtuzumab and posttransplant tacrolimus monotherapy.


RESULTS
With a total of 395 consecutive primary recipients, de novo malignancy(s) developed in 61 (15%) patients, with PTLD in 52 (13%), and nonlymphoid cancer (NLC) in 13 (3.2%). Malignancy was donor driven in 3 (4.6%) recipients and associated with graft-versus-host disease in 7 (11.4%). Children were at a significantly higher risk (P<0.001) of PTLD, and adults were more vulnerable (P=0.01) to NLC. With multivariate analyses, type of immunosuppression, recipient age, splenectomy, and treatment of rejection were significant PTLD risk factors.


CONCLUSIONS
Despite pretransplant lymphoid depletion, preemptive antiviral therapy and minimization of posttransplant immunosuppression significantly reduced PTLD morbidity (P=0.0001) and mortality (P=0.001) with no impact on NLC. Patient survival was also improved (P=0.0001) with 91% at 1 year and 75% at 5 years.
Abu-Elmagd
Kareem M
KM
Department of Surgery, Thomas E. Starzl Transplant Institute, University of Pittsburgh, Pittsburgh, PA 15213, USA. abuelmagdkm@upmc.edu
Mazariegos
George
G
Costa
Guilherme
G
Soltys
Kyle
K
Bond
Geoffrey
G
Sindhi
Rakesh
R
Green
Michael
M
Jaffe
Ronald
R
Wu
Tong
T
Koritsky
Darlene
D
Matarese
Laura
L
Schuster
Bonnie
B
Martin
Lillian
L
Dvorchik
Igor
I
Nalesnik
Michael A
MA
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000818:Animals; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D000998:Antiviral Agents / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D004359:Drug Therapy, Combination; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007422:Intestines / Q000637:transplantation*; D008212:Lymphocyte Depletion / Q000401:mortality; D008232:Lymphoproliferative Disorders / Q000453:epidemiology* / Q000401:mortality; D008875:Middle Aged; D009369:Neoplasms / Q000453:epidemiology* / Q000401:mortality; D016377:Organ Transplantation / Q000401:mortality / Q000706:statistics & numerical data; D011183:Postoperative Complications / Q000453:epidemiology* / Q000401:mortality; D011817:Rabbits; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate; D014781:Viscera / Q000637:transplantation*
D000961:Antilymphocyte Serum; D000998:Antiviral Agents; D007166:Immunosuppressive Agents