Abu-Elmagd, K

Furukawa, H

Green, M

Irish, W

Kadry, Z

Kusne, S

Manez, R

Reyes, J

Starzl, TE

Todo, S

Tzakis, A

PubMed

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Factors Associated With Recurrent Cytomegalovirus Disease After Small Bowel Transplantation R. Maliez, S. Kusne, K. Abu-Elmagd, J. Reyes, W. Irish, M. Green, H. Furukawa, Z. Kadry, A. Tzakis, S. Todo, and T.E. Starzl CYTOMEGALOVIRUS (CMV) disease results from a complex interplay among a variety of factors. the consequences of which are differences in the incidence and severity of CMV disease across different transplant popu-lations. '-3 In May 1990. the small bowel transplantation (Sax) program was initiated at our institution. In this study we analyze the incidence and timing of CMV disease after sax and we assess risk factors for CMV disease in this new transplant population. MATERIALS AND METHODS Patient Population From May 1990 to March 1993.40 patients underwent SBx at the University of Pittsburgh Medical Center. Four patients died during the first month after transplantation and were excluded from the study. The study population included 36 patients who received 38 grafts. There were 20 adults and 16 children with an age range between 6 months and 50 years. Thirteen patients (36%) received an isolated SBx. 18 (50%) received SBx and liver and 5 (14%) receIved multi visceral grafts. Immunosuppression and CMV Prophylaxis Immunosuppression included FK 506 and steroids as previously described.' Twenty·five patients (69%) were treated also with azathioprine. Twenty·two patients received ganciclovir prophy· laxis between 21 and 90 days after SBx. Sixteen children and I adult received only CMV·seronegative blood products. RESULTS Fourteen patients t39%) developed 25 episodes of CMV disease. Six had a single episode. 5 had 2 episodes. 2 had :; episodes. and I had 4 episodes. The first. second. and third episodes of CMV disease occurred at a mean of 48 :!: 23. 131 :!: 68. and 173 :!: 19 days. respectively. after transplantation. The types ofCMV disease were: 20 (80%) enteritis. 2 (8%) hepatitis. 2 (8%) pneumonitis. and I (4%) syndrome. Table I shows the relationship between donor/ recipient CMV serologic status and the frequency ofCMV disease. Table 1. Incidence ot CMV Dlsea .. after Small 80_1 Transplantation Donor,Reclplent CMV Status In ~ 381 D-,R- (16) D-,R+ (8) Dr R+ (3) D+R- (11) Pahents In = 141 \ °0) o 4 (SO) 2 (75) 8 (73) Episooes In = 251 o 6 3 16 Univariate and multivariate analyses to study risk fac-tors for CMV disease were performed using Cox's propor-tional hazards model. Factors analyzed included age, type of transplantation. donor and recipient serologic status, use of ganciclovir prophylaxis. blood products transfused, the cumulative blood level of FK 506, and cumulative doses (adjusted to weight) of OKT3, azathioprine, and pulse and maintenance doses of steroids. Multivariate analysis showed that the factors associated with a first episode of CMV disease were: CMV-seronegative recipi-ent of a CMV-seropositive graft (relative risk [RR] 6.4. 95% confidence interval [CI] 1.7 to 24.7. P = .007). the cumulative blood level of FK 506 (RR 2.3,95% CI 1 to 5.2, P = .04). the cumulative dose of pulse of steroids (RR 2.6. 95% CI 1 to 6.9. P = .06) and the cumulative dose of maintenance steroids (RR 5.2. 95% CI 1.1 to 23.\. P = .03). The only 2 factors independently associated with recurrent CMV disease were CMV-seronegative recipient of CMV-seropositive graft (RR 10.1. 95% CI 1.9 to 52.5. P = .006) and the cumulative doses of steroid boluses (RR 15.1.95% CI 1.6 to 125.4. P = .01). DISCUSSION This study showed that sax transplantation is associated with a high incidence of CMV disease. Although the morbidity associated with CMV infection is quite variable. 2 factors have been associated with an elevated incidence of CMV disease: primary CMV infection after transplan-tation and the type and amount of immunosuppression given. Primary CMV infection occurred in 73% of CMV-seronegative recipients who received grafts from CMV· seropositive donors. and accounted for 64% of episodes of disease. This contrasts with the lack of infection and disease in seronegative recipients of seronegative grafts. However. the morbidity of CMV infection was also high in secondary infections. because 55% of CMs·~eropositive recipients developed disease. The multivariate analysis showed that the cumulative FK 506 levels. and amount of steroid given in boluses and for maintenance. were also risk factors for CMV disease. This suggests that the From the Departments of Surgery and MedICine. University of Pittsburgh. Pittsburgh. PennsylvanIa. Address repnnt requests to S. Kusne. MD. University of Pitts· burgh. Transplantation Institute. 3601 Fifth Avenue. 5C Falk. Pittsburgh. PA 15213. c 1994 by Appleton & Lange 0041·1345/94/$3.001 + 0 1422 Transplantation Proceec1mgs. Vol 26. No 3 (June). 1994: pp 1422-1423 RECURRENT CMV DISEASE increased immunosuppression that many of these patients required also played an important role in the high inci-dence of CMY disease after SBx. Because long courses of ganciclovir prophylaxis were not sufficient to prevent CMY disease. new strategies are needed. A voiding trans-plantation of CMY -seropositive grafts into CMY -seroneg-ative recipients and new approaches to prevent overimmu-nosuppression are 2 potential alternatives to decrease the incidence of CMY disease in SBx. -------- ---------------------------------1423 REFERENCES 1. Gorensek MJ. Stewart RW. Keys TF. et al: J Infect Dis 157:515. 1988 2. Rubin RH. Tolkotf-Rubin NE. Oliver D. et aI: Transplanta-tion 40:243. 1985 3. Bronster O. Makowka L. Jaffe R. et al: J Med ViroI24:423. 1988 4. Abu-Elmagd K. Todo S. Tzakis. et al: Transplant Proc (in press) 

Factors associated with recurrent cytomegalovirus disease after small bowel transplantation

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Factors associated with recurrent cytomegalovirus disease after small bowel transplantation

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