Bueno, J

Green, M

Jabbour, N

Kauffman, M

Kocoshis, S

Nalesnik, M

Reyes, J

Starzl, TE

Todo, S

Yunis, E

PubMed

Name not available

Epstein Barr Virus associated posttransplant lymphoproliferative disease after intestinal transplantation

D-Scholarship@Pitt

I ! ; I i: . __ ._------------Epstein Barr Virus Associated Posttransplant LYmphO~~Ii~r~e Disease After Intestinal Transplantation J. Reyes, M. Green, J. Bueno, N. Jabbour, M. Nalesnik, E. Yunis, S. Kocoshis, M. Kauffman, S. Todo, and T.E. Starzl PREVIOUS reports of posttransplant lymphoprolifera-tive disease (PTLD) after intestinal transplantation described a high incidence with consequent significant morbidity and mortality. 1 We present the clinicaVpatholog-ical spectrum of PTLD occurring after intestinal transplan-tation with particular emphasis on risk factors and effect on patient and graft survival. MATERIALS AND METHODS Case Material Between May 1990 and June 1995, 73 patients received 78 intesti-nal transplants under tacrolimus and steroid immunosuppression. These included the following grafts: small bowel (SB) (n = 28), liver/small bowel (LSB) (n = 35), and multivisceral (MV) (n = 15) recipients. There were 41 children and 32 adults transplanted; their ages ranged between 0.5 and 58.1 years. Immunosuppression, donor. and recipient surgical procedures, and nutritional manage-ment have been described elsewhere." Pathological Studies All available surgical and autopsy specimens were reviewed. The evaluation of PTLD lesions included histopathology, analysis of clonal status. and demonstration of EBV (by in-situ hybridization [EBERl). PTLD was defined as the presence of lymphoid growths from any site after transplantation. These lymphoid growths may present as tumor. destructive infiltrates. with or without clonal proliferations. and show EBER positivity. Recipient EBV serology was obtained preoperatively. RESULTS Patient Population and Tumor Incidence Fourteen cases (19%) of PTLD were identified. The overall incidence in the adult and pediatric recipients was 9.3% and 26.8%. respectively. Seven occurred in males and 7 oc-curred in females (male/female ratio 1/1). Eleven patients were children with a median age of 2.8 years. The time between the date of organ transplant and the date of disease presentation ranged between 24 days to 5 years (median time of 9 months). The recurrence of PTLD at retransplantation produced 16 cases which were distributed relative to graft type as follows: three cases after SB (10.77<). seven cases after LSB graft (20%). and 6 cases after MV grafts (40%). There were a tot a I of 18 episodes of PTLD among these 14 recipicnts (recurrence rate of 28.5%). Persistent. intractahle diseuse was seen in four patients. with eventual dcuth in three. Pathological Features of PTLD The range of histology was that of lymphocytic infiltrates with a monomorphic and/or polymorphic appearance. Plas-macytoid features were seen in the chronic cases. Depend-ing on the stage of the PTLD, there was some admixture of immunoblastic cells as well as eosinophils and polymorpho-nuclear cells. Reed-Sternberg-like cells were seen in only three cases in a setting of very atypical lymphocytes and immunoblastic cells, with necrosis. Two patients presented a unique spindle cell tumor (of smooth muscle origin) in the native and allograft intestine as previously reported.3 Clonal analysis was performed in nine patients: the lesions were monoclonal in seven patients and polyc1onal in two. Evidence of EBER positivity was seen in all cases. Serologic evidence of prior EBV infection was found in 10 patients. The most common region of involvement was the gastro-intestinal tract, principally allograft but also native. A lymphadenopathic presentation was seen in only one pa-tient and was amenable to rapid and complete remission of disease with preservation of graft function. Seven of 14 patients received OKT3. A history of splenectomy was noted in 12 of 14 recipients. Treatment of PTLD Therapy consisted of reduction of immunosuppression combined with intravenous acyclovir or ganciclovir for as long as the lesions were present. Alpha interferon and foscarnet were used in selected cases. Two of the patients who were placed on interferon suffered significant rejection episodes post-interferon therapy. In two cases the immuno-suppression was stopped completely while there was evi-dence of clinical disease: however. one patient suffered severe rejection post-withdrawal of immunosuppression which required augmentation of immunosuppression. Hy-perimmuneglobulin therapy was used in four patients. Chemotherapy was used in one patient with fulminant disease. OUTCOME Seven of the 14 patients diagnosed with PTLD have sur-vived (mortality of 50%). Only five of the surviving patients have had complete remission of their disease. whereas two From the Pittsburgh Transplantation Institute, UniverSity of Pittsburgh. Pittsburgh Medical Center and Children's Hospital of Pittsburgh. Departments of Infectious Disease (M.G.), Pathology (E.Y.). and Gastroenterology (S.K .. T.E.S.). Address reprint requests to Jorge Reyes. MD, Associate Professor of Surgery. Pittsburgh Transplantation Institute, 3601 Fifth Avenue. 4C, Falk Clinic. Pittsburgh, PA 15213. c) 1996 by Appleton & Lange 0041-1345/96/$3.00/ +0 2768 Transplantation Proceedings, Vol 28. No 5 (October). 1996: pp 2768-2769 INTESTINAL TRANSPLANTATION patients continue to have lesions and are under therapy. Four of the surviving patients have retained their original grafts and are TPN free. Retransplantation was performed in two cases, with one death. A SB recipient was retrans-planted after complete resolution of disease and has sur-vived. He is presently off TPN. Of the seven patients who died, all were identified to have residual PTLD. Causes of death included: PTLD (n = 4), intestinal allograft rejection (n = 2), and iatrogenic hypematremia (n = 1). DISCUSSION The mainstay of therapy continues to be judicious reduction of immunosuppression with antiviral therapy. However, though this has been generally successful for the treatment of PTLD in recipients of other organs, this has not been so in the intestinal transplant population. Rebound intestinal allograft rejection has occurred early, without complete resolution of the PTLD disease. This has percipiated sig-nificant morbidity as well as patient and graft loss not only from PTLD, but also as a result of rejection. The addition of hyperimmuneglobulin therapy in this 2769 patient population was stimulated by the use of EBV PCR, and its consequent decrease in one patient. However, the role of this type of therapy as well as the use of alpha interferon or foscamet remains to be determined. In light of the experience reported with EBV peR in this issue,5 it is likely that both early diagnosis added to immunemodulation and antiviral therapy may be successful in the future. PTLD was treated successfully in three surviving patients, who presently maintain a base line immunosuppression using tacrolimus and steroids. REFERENCES 1. Reyes J, Tzakis AG, Bonet H, et al: Transplant Proc 26(3): 1426, 1994 2, Todo S, Tzakis AG, Abu-Elamgd 1(, et al: Ann of Surgery 216(3):223, 1992 3. Lee ES, Locker J, Nalesnik M, et al: N Eng J of Med 332:19, 1995 4. Nalesnik MA and Starzl TE: Transplantation Science 4(1):61, 1994 5. Green M, Reyes J, Jabbour N: Transplant Proc 28:(this issue), 1996 

Epstein Barr virus associated posttransplant lymphoproliferative disease after intestinal transplantation

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Epstein Barr virus associated posttransplant lymphoproliferative disease after intestinal transplantation

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