DOUGLAS, L

ESQUIVEL, CO

IWATSUKI, S

KONERU, B

MAKOWKA, L

MARSH, JW

SCANTLEBURY, VP

STARZL, TE

TODO, S

TZAKIS, AG

English

PubMed

Koneru, B

Scantlebury, VP

Makowka, L

Esquivel, CO

Todo, S

Tzakis, AG

Marsh, JW

Iwatsuki, S

Douglas, L

Starzl, TE

Name not available

Infections in pediatric liver recipients treated for acute rejection

D-Scholarship@Pitt

Infections in Pediatric Liver Recipients Treated for Acute Rejection Baburao Koneru, Velma P. Scantlebury, Leonard Makowka, Carlos O. Esquivel, Satoru Todo, Andreas G. Tzakis, J. Wallis Marsh, Shunzaburo Iwatsuki, Laura Douglas, and Thomas E. Slarzl M URINE MONOCLONAL antibody OKTJ (ortho-clone OKT3). is a powerful immunosuppressant and has been shown to be very effective in reversal of acute rejection following kidney, liver a nd heart transplants. I·) As with any kind of immunosuppression, one would expect that use of OKTJ might be associated with increased inci-dence of infections. However, there have been only a few detailed studies of infections following the usc of OKTJ and even fewer comparing them to infections that occur when steroids only were the mainstay of anti-rejection therapy.,·5 Hence we undertook a detailed retrospective review of infec-tions that occurred in children receiving OKT3 for hepatic allograft rejection and compared them to infections that occurred in a similar group of children whose rejection was treated with steroids only. PATIENTS AND METHODS Eighty cases were reviewed from a group of pediatric patients having li~er transplants at the Children's Hospital of Pittsburgh and the University of Pittsburgh betlloeen January 198 I and June 1986. To be included. patients should have received treatment for clinical or biopsy proven rejection within six months following the primary transplant and survived for at least seven or more days upon its completion. Patients were excluded if rejection therapy was aborted « 7 doses of OK T3 or less than 3 days of steroids in a five day oral recycle). or if they received polyclonal antilymphocyte globulin. Symptomatic infections lIoere identified and grouped by strict adher-ence to predefined criterta. The study spanned two periods of rejection therapy. Until October 1984. study patients received only addilional sleroids to treat rejection. From October 1984. OKT3 became available to treat rejection either alone. or in addition to steroids. The paticnl's course was rc:vie"'c:d from the time of trans-plant. up to 1 gOdays or 90 days after completion of rejection therapy ",hichevcr was longer. Data on pre-transplant characteristics. tech-nical complications. infections. lotal amount of immunosuppression. retransplants and deaths were collected. Statistical Analysis Analyses "'cre performed on a mainframc computer using a statisti-cal program for social sciences (SPSS) for comparing proportions and student's t-test for comparing mean values. P values or <0.05 were considered significant. RESULTS Twenty-seven patients had rejection treated with onl)' addi-tional steroids. Fifty-three received OKTJ as part of their rejection treatment. The patient characteristics in both groups arc outlined in Table I. Immunosuppression Baseline immunosuppression was essentially similar in both groups and has been described in detail before.' Maintenance cyclosporine (CyA) and steroids were continued during OKT3 treatment. Twenty of twenty·seven patients in steroid group and 27/53 in OK TJ selected at random. had their total amount of intravenous and oral CyA. bolus steroids and prednisone calculated for the entire follow-up period as mean dose in mg/kg/day. These values shown in Table I. showed no statistical significance between the groups. Infections The overall infection rate in the steroids only group was 66.6% (18/27). Viral infections occurred in 37% (10/27). fungal infections in 14.8% (4/27) and bacterial infections in 44.4% (12/27) of patients. Compared to this viral infections occurred in 45.2%. (24/53). fungal infections in 20.7% (II/53) and bacterial infections in 47.1 % (25/53) of patients receiving OKT3. Two in the OKTJ group (3.7%) but none in the steroid group developed pneumocystis pneumonitis. These results are tabulated in Table 2. There is no statisti-cally significant difference between the two groups either in the overall incidence of infections or in specific occurrence of viral. fungal or bacterial infections .. Technical Complications In the steroid group. 9 patients (33%) had 12 technical complications whereas 18 in OKT3 group (34%) had 31 complications. The o\erall infection rates in both groups were the same EUUKU~FK The majority of the infections in this subgroup of patients were bacterial. Retransplants and Dealhs Seven patients in the steroids group required 9 retransplants during the follow-up period. Approximately half of them (5/9) were for rejection. In the OKT3 group, 15 patients required 16 retransplants. 6/16 were for rejection. Three deaths occurred in the steroid group versus II in the OKT3 group. Two of the deaths in the steroid group and 9 of the deaths in the OKT3 group were directly attributable to infection. There was no statistical significance either in the rate of retransplants or deaths between the two groups. From the Department of Surgery. The Universily of Pillsburgh School of Medicine and the Children's Hospital of Pillsburgh. Pittsburgh, PA. USA. Address reprint requests to Baburao Koneru. MD. Universily Hospilal. Departmenl 01 Surgery·E325. 150Bergen St, Newark NJ 07103. USA. Supported by Research GranlS from the Veterans Administra· tion Project Granl OK 29961 Irom the National Institutes of Health, Be:hesda, Maryland. USA. e 1989 by Appleton & Lange. Inc. 0041-1345/89/$3.001 +0 Transplantation Proc •• dings. Vo121. No 1 (February). 1989: pp 2251-2252 2251 K--"K----~-· -----------2252 Table 1. CharacterllUes of the Patient. Treated for Rejection Mean age (months) Sex males:lemales Mean weight (kg) Pretransplant (mean values) WBC/mm' Steroid. Only (n - 27) 60 13: 14 16 .• 6.08 OKT3 (n - 63) 66 26:27 19.7 7." Total bilirubin mg/dl 18 18.1 Prothrombin time in sec. 16.1 16.8 Biliary atresia 55% 45% Prior abdominal surgery 55% 56% Immunosuppression given as mgm/kg/d (mean values) I.V. CyA 1.29 1.49 P.O. CyA 19.8 29.2 Bolus steroida 0.92 0.85 Oral prednisone Mean lollow·up days DISCUSSION 1.31 171 1.21 161 Most of the reports describing the clinical use of OKT3 have dealt with its efficacy in reversing established allograft reject ions. 1.1.' The problems of infections had not been reported in detail. Since then a few reports have studicd the topic of infections in renal recipients. Sanoh et al in their comparison of infections in 2 groups of renal recipients with acute rejection treated and not treated with OKT3 found higher incidence of viral and bacterial infections in the OKT3 group.s The number of cases with fungal infections were too small to compare. In adult liver recipients receiving OKT3. Singh et al reported a higher incidence and more serious infections with herpes group of viruses.' However. the other patients in that report have nct all been treated for rejection. In 51 consecu-tive pediatric liver recipients Breinig et al showed a different pattern of viral infections compared to adults.' Fewer of them had primary CMV and HSV infections. Adenoviral infections. not seen in adult liver recipients. were encoun-tered. Our study shows no difference in the overall rate of infections between the two groups of patients. This is still true even when individual categories of infections are consid-ered separately (Table 2). Liver transplant patients also have higher incidence of fungal infections compared to other organ allograft recipients. This is probably related to higher incidence of technical problems and longer operative time in liver recipients.' Fungal infections also increase with increased amounts of steroids. The incidence of fungal infections in our two groups of patients were similar and were not statistically significant (14.8% in steroids versus 20. T~ in OKT3). Pediatric liver recipients have higher incidence of techni-cal complications compared to adults. 1o These patients develop a variety of fungal and bacterial infections. The KONERU. SCANTLEBURY. MAKOWKA ET AL Table 2. Various Infections Encountered In Patient. Treated for Rejection Total number of palienlS wilh in·· fections Patients with viral infections Cytomegalovirus Herpes simplex virus (HSV) Adenovirus (A V) Varicella zoster Epstein·Barr virus (EBV) Parainftuenza Patients with fungal infections Candida Aspergillus Nocardia Patients with bacterial infec· tions Steroida Only n - 27 18 (66.6%) 10 (37%) 3 4 4 (t 4.8%) 3 12 (44.<4%) OKT3 n - 53 36 (67.9%) 24 (45.2%) 10 8 4 1 4 1 1 1 (20.7%) 10 2 25 (.7.1otb) overall incidence of infections in patients with technical complications in the present series has been very high but it is the same in both groups. In a report on hepatic retransplantation Shaw et al found that approximately 50% of retransplants in children were for rejection:o In our study retransplantation rate for rejection was 55% in the steroid group and 37.5% for OKT3 group, but was not significant statistically. In conclusion. our present study shows that overall infec-tion rate. rates of viral. fungal and bacterial infections and deaths secondary to infection were similar in groups of patients receiving OKT3 compared to patients whose rejec· tion was treated .... ith only steroids. The retransplantation rates for rejection .... ere again not significantly different in the two groups. REFERENCES 1 Goldsleln G. Schindler J. Tsai H. et al: ~eII" Engl J Mcd 313:337·342. 1985 2. Fung JJ. Markus BH. Gordon RD. et al: Transplant Proc 19:37·44. 1987 3. Gilbert EM. Eis\loinh CC. Renlund DC. ct al: Transplanl Proc 19(suppl 1):45·50. 1987 4. pingh~K Dummer JS. Kusnc S. Breinig MK. Armstrong JA. Ma kowka L. Slarzl TE. Ho ~1 J Infccl Dis 158: 124·131. 1988 S. Sanoh C. Stralla RJ. Fox Be. Sollinger HW. Belzer FO. ~1aki DC: Transplantation 45:68-73. 1988 6. Starzl TE. Iwalsuki S. Shallo BW. el al: 17:250. 1985 7. Delmonico FL. Cosimi AB: Surg Gynecol Obstel 166:89·98. 1988 8. Breinig MI<. Zilelli B. Slarzl TE. et al: J Infecl DIS 156:273· 279. 1987 9. Wajslculuk CP, Dummer JS. Ho M. cl al: Transplantation 40:3<47·353. 1985 10. Shaw BW. Gordon RD. I"'alsuki S. el al: Transplant Proc 17:264-271.1985 .......... ____ A--C''''J ___ u"''s .. -:.jO!;_ec __ .n' __ • __________ ---------------------------------~-------K-

INFECTIONS IN PEDIATRIC LIVER RECIPIENTS TREATED FOR ACUTE REJECTION

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INFECTIONS IN PEDIATRIC LIVER RECIPIENTS TREATED FOR ACUTE REJECTION

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