title: Lymphoproliferative disorders and de novo malignancies in intestinal and multivisceral recipients: improved outcomes with new outlooks.
abstract: 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.
authors.affiliation: Department of Surgery, Thomas E. Starzl Transplant Institute, University of Pittsburgh, Pittsburgh, PA 15213, USA. abuelmagdkm@upmc.edu
authors.forename: Kareem M
authors.initials: KM
authors.lastname: Abu-Elmagd
authors.forename: George
authors.initials: G
authors.lastname: Mazariegos
authors.forename: Guilherme
authors.initials: G
authors.lastname: Costa
authors.forename: Kyle
authors.initials: K
authors.lastname: Soltys
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Bond
authors.forename: Rakesh
authors.initials: R
authors.lastname: Sindhi
authors.forename: Michael
authors.initials: M
authors.lastname: Green
authors.forename: Ronald
authors.initials: R
authors.lastname: Jaffe
authors.forename: Tong
authors.initials: T
authors.lastname: Wu
authors.forename: Darlene
authors.initials: D
authors.lastname: Koritsky
authors.forename: Laura
authors.initials: L
authors.lastname: Matarese
authors.forename: Bonnie
authors.initials: B
authors.lastname: Schuster
authors.forename: Lillian
authors.initials: L
authors.lastname: Martin
authors.forename: Igor
authors.initials: I
authors.lastname: Dvorchik
authors.forename: Michael A
authors.initials: MA
authors.lastname: Nalesnik
mesh_terms: 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*
chemical_list: D000961:Antilymphocyte Serum; D000998:Antiviral Agents; D007166:Immunosuppressive Agents