Reduction of immunosuppression as initial therapy for posttransplantation lymphoproliferative disorder(★)

Abstract

Reduction of immunosuppression (RI) is commonly used to treat posttransplant lymphoproliferative disorder (PTLD) in solid organ transplant recipients. We investigated the efficacy, safety and predictors of response to RI in adult patients with PTLD. Sixty-seven patients were managed with RI alone and 30 patients were treated with surgical excision followed by adjuvant RI. The response rate to RI alone was 45% (complete response-37%, partial response-8%). The relapse rate in complete responders was 17%. Adjuvant RI resulted in a 27% relapse rate. The acute rejection rate following RI-containing strategies was 32% and a second transplant was feasible without relapse of PTLD. The median survival was 44 months in patients treated with RI alone and 9.5 months in patients who remained on full immunosuppression (p = 0.07). Bulky disease, advanced stage and older age predicted lack of response to RI. Survival analysis demonstrated predictors of poor outcome-age, dyspnea, B symptoms, LDH level, hepatitis C, bone marrow and liver involvement. Patients with none or one of these factors had a 3-year overall survival of 100% and 79%, respectively. These findings support the use of RI alone in low-risk PTLD and suggest factors that predict response and survival.

Figure 1

Overall survival of patients with PTLD who were treated with reduction of immunosuppression (RI) alone as initial therapy (n=67), complete surgical excision of a PTLD lesion, followed by adjuvant RI (n=30), and no RI throughout treatment (n=23). Survival estimates are plotted using the Kaplan-Meier method. P=0.07 for RI alone versus No RI represents a logrank test.

Figure 2

Proportions of responding (Complete Response + Partial Response) and non-responding (Stable Disease + Progressive Disease) patients with PTLD following treatment with RI alone analyzed according to clinical and pathologic characteristics. Odds ratios indicate the difference in likelihood of response between subgroups and P-values indicate significance level in a logistic regression model. * P<0.05. A. Representative variables from Table 4. B. Prediction of response to RI using a summary of 3 independent adverse factors: Age≥50, advanced stage (3–4 vs. 1–2) & bulky disease (mass>7cm).

Figure 3

Overall survival of patients with PTLD who were treated with reduction of immunosuppression (RI) alone as initial therapy stratified using a survival model that includes 7 prognostic factors: Age≥50, serum LDH>2.5×ULN, hepatitis C, liver involvement, bone marrow involvement, B symptoms, dyspnea at presentation. Survival estimates are plotted using the Kaplan-Meier method. P-values represent a logrank test across strata. Total n=64 patients with complete data.