Clinical lung and heart/lung transplantation
Lymphoproliferative disease after lung transplantation: comparison of presentation and outcome of early and late cases

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Abstract

Background: Post-transplantation lymphoproliferative disease (PTLD) after lung transplantation has not been fully characterized. In previous studies, the incidence has varied substantially, and most cases have been reported during the first year after transplantation. The purpose of this study was to review our center’s experience with PTLD and to analyze the pattern of disease and determinants of outcome.

Methods

Among 494 adult lung (n = 491) or heart–lung (n = 3) recipients, 30 cases of PTLD were retrospectively identified. The cases were classified by site(s) of involvement, histology and time of onset (early, ≤1 year, and late, >1 year after transplantation). The outcome of each case was ascertained, and risk factors for death were analyzed in a multivariate model.

Results

PTLD was identified in 30 (6.1%) of the recipients during 1,687 patient-years (median 2.8 years) of follow-up. The incidence density was 1.8 cases per 100 patient-years. Fourteen cases were diagnosed during the first year after transplantation, and 16 cases in subsequent years. The incidence density was significantly higher in the first year than in later years (3.3 cases/100 patient-years versus 1.3 cases/100 patient years; p < .008). Presentation in the thorax and involvement of the allograft were significantly more common in the early cases (thorax: 12 of 14, 86%; allograft: 9 of 14, 64%) than in the late cases (thorax: 2 of 16, 12%; allograft: 2 of 16, 12%). There was no difference in survival after the diagnosis of PTLD between the early and late cases, but survival time after diagnosis was significantly longer in cases with, than those without, allograft involvement (median 2.6 years vs 0.2 year, respectively; log rank p = 0.007).

Conclusions

The presentation and pattern of organ involvement of PTLD after lung transplantation is related to the time of onset. Disease in the thorax and involvement of the allograft are common in the first year after transplantation, but other sites, especially the gastrointestinal tract, predominate later. PTLD that is confined to the allograft appears to have a somewhat better prognosis than disease that involves other sites.

Section snippets

Patients

All patients who underwent lung or heart–lung transplantation at Barnes–Jewish Hospital, a tertiary care affiliate of Washington University School of Medicine, St Louis, MO, between July 1, 1988 and January 1, 2000, were included in this study. The assessment of outcomes was continued through April 15, 2000, the end of the study period.

PTLD was diagnosed in 30 of 494 recipients. For reference in this study, the cases of PTLD were serially numbered in chronologic order according to the

Diagnosis, classification and management of PTLD

Throughout the study period, evaluation of clinically apparent abnormalities led to the detection of PTLD. The diagnosis was confirmed by biopsy or surgical excision (n = 26), fine needle aspiration (n = 2) or autopsy (n = 2). One of the cases that was initially diagnosed by needle aspiration was subsequently corroborated by post-mortem pathology. The date of confirmation was used as the date of diagnosis in the analyses.

A pathologist (M.D.K.) who was blinded to the clinical information

Data analysis

The date of transplantation, date of death or last follow-up, cause of death, site(s) of PTLD, treatment for PTLD and response to treatment were recorded. Age at transplantation and age at PTLD diagnosis were calculated. For statistical analysis, cases were classified according to the time of onset and the site(s) of PTLD and were analyzed in several ways: “Early” vs “Late”; “Thoracic” (any site in chest, with or without an extrathoracic site) vs “Extrathoracic” (sites exclusively outside

Results

Between July 1, 1988 and January 1, 2000, 494 adult patients underwent lung (n = 491) or heart–lung (n = 3) transplantation at Barnes–Jewish Hospital (Table I). Kaplan–Meier survival rates for these recipients were 84% at 1 year, 70% at 3 years and 52% at 5 years after transplantation. The mean (±SD) duration of observation for the recipients was 3.4 ± 2.6 years (median 2.8 years), and the study included 1687 patient-years of follow-up. Three hundred eighty-four recipients had follow-up beyond

Discussion

Post-transplantation lymphoproliferative disease has become a well-known complication of lung transplantation, but it has not been characterized completely. A synopsis of the published series of PTLD after lung transplantation is presented in Table IV. Most studies have reported small cohorts of recipients that have been monitored for a relatively short time after transplantation. Although the follow-up period has varied and has not always been clearly specified, the incidence of PTLD in these

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    Supported by the National Heart, Lung and Blood Institute; National Institutes of Health (Grant K23 HL04236) (Dr Yusen); and by the Rosemary and I. Jerome Flance Professorship in Pulmonary Medicine (Dr. Trulock).

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