Reduction of Immunosuppression as Initial Therapy for Post-Transplantation Lymphoproliferative Disorder: Analysis of Efficacy, Safety and Prognostic Factors.

Abstract Abstract 103 Post-transplantation lymphoproliferative disorder (PTLD) is a heterogeneous group of lymphoid neoplasms arising in immunosuppressed organ transplant recipients. While it has long been known that reduction of immunosuppression (RI) is an effective therapy, previous reports on RI alone are of limited value due to small numbers of patients. We analyzed the efficacy, safety and predictors of response to therapy in a series of 162 organ transplant recipients diagnosed with PTLD at the University of Pennsylvania between 1988 and 2008. We analyzed clinical and pathological characteristics, response to therapy, graft outcome and survival of patients treated with RI alone as initial therapy for PTLD in comparison to patients who were treated with other therapies. We used logistic regression to identify predictors of response, and Cox regression to identify predictors of survival, in patients treated with RI. We identified 67 patients who were treated with RI alone and additional 30 patients who were treated with complete surgical excision of a localized lesion followed by adjuvant RI. We compared these patients with 51 evaluable patients who were treated with other modalities upfront. The overall response rate to RI alone was 45% (CR 37%, PR 8%). Sixty percent of the patients required additional therapy for failure or relapse, but of patients who experienced a complete response, only 17% later required therapy for relapsed disease. The most common second-line therapies were rituximab (40%), followed by chemotherapy (39%) and radiotherapy (15%). Forty percent of patients had an acute rejection episode. Five patients were re-transplanted successfully without recurrence of PTLD. In the group of patients who were treated with adjuvant RI following surgery, only 13% relapsed. Median survival was 44 months for RI alone (not reached for adjuvant RI). Lack of bulky disease, multiple previous allografts and younger age predicted better response to RI by univariate analysis. Notably, EBV status, pathological subtype and type of transplanted organ were not associated with significant differences in response to RI. A step-wise multivariate logistic regression analysis confirmed that older age and bulky disease were independent predictors of RI failure. Survival analysis was done on patients treated with RI alone and separately on our entire cohort of 153 evaluable patients, validating traditional prognostic factors such as B symptoms, visceral involvement (liver), abnormal LDH and anemia ( Table 1 ). To conclude, in our large, single-center series, RI resulted in responses in 45% of patients, with many patients cured. Although graft rejection was common, it was manageable in some patients and re-transplantation was feasible in others. The strongest predictors of response to RI are younger age and lack of bulky disease. These findings support the use of RI alone as initial therapy for PTLD. Table 1 . Predictors of mortality in patients treated with RI alone and in all evaluable patients. Variable RI alone (n=67) All evaluable patients (n=153) HR (95% CI) p-value HR (95% CI) p-value Transplanted organ (kidney vs. non-kidney) 0.635 (0.32, 1.26) 0.191 0.649 (0.41, 1.04) 0.071 Late (≥1 yr) vs. Early ( 1.137 (0.77, 1.68) 0.519 1.147 (0.88, 1.49) 0.308 Monomorphic vs. Polymorphic 1.159 (0.60, 2.25) 0.662 1.234 (0.78, 1.95) 0.37 EBV-positive vs. EBV-negative 0.781 (0.38, 1.61) 0.502 0.932 (0.54, 1.61) 0.8 B symptoms 2.04 (1.01, 4.10) 0.046 1.593 (0.998, 2.54) 0.051 Weight loss 2.03 (1.08, 3.82) 0.028 1.702 (1.09, 2.65) 0.018 Dyspnea 2.68 (1.17, 6.13) 0.02 2.337 (1.26, 4.33) 0.007 Stage (I/II vs. III/IV) 1.459 (0.78, 2.75) 0.242 1.526 (0.99, 2.36) 0.056 Bulky disease 1.06 (0.44, 2.56) 0.9 1.033 (0.52, 2.07) 0.928 Extranodal disease 1.675 (0.77, 3.65) 0.194 1.388 (0.77, 2.51) 0.279 Liver involvement 2.79 (1.26, 6.20) 0.012 1.668 (0.9, 3.09) 0.105 Renal failure 2.05 (0.99, 4.23) 0.052 1.45 (0.85, 2.46) 0.169 Abnormal LDH 1.821 (0.88, 3.78) 0.108 2.043 (1.13, 3.69) 0.018 Anemia 2.227 (0.78, 6.33) 0.133 2.476 (1.19, 5.16) 0.016 Thrombocytopenia 0.676 (0.33, 1.40) 0.29 0.701 (0.45, 1.1) 0.125 Disclosures: No relevant conflicts of interest to declare.