Post Transplant Lymphoproliferative Disorders: Prognostic Features and Rituximab Impact In a 120 Case Single Institution Series
Authors: Montanari Francesca , Bhagat Govind , Seshan Venkatraman , Clark-Garvey Sean , Zain Jasmine M. , Diefenbach Catherine S. , McCormick Erin , Conroy Meaghan , Crook Meghan , Alobeid Bachir , O'Connor Owen A. 
Published: October 2019

Abstract
Abstract 4151
Post-transplant lymphoproliferative disorder (PTLD) is a broad spectrum of lymphoproliferative disorders that can occur after solid organ transplant or hematopoietic stem cell transplant. The incidence ranges from 1% to 20% depending on the type of organ graft, the intensity of the immunosuppression and the Epstein-Barr virus (EBV) serostatus. It represents a serious and potentially life threatening complication, with reported mortality rate up to 40–50%. According to the World Health Organization classification system, PTLD are classified as early lesions (EL), polymorphic (p-PTLD), monomorphic (m-PTLD), and Hodgkin-like (HL). Here we analyzed the prognosis and clinical characteristics of 120 patients diagnosed and treated over a 19-year period (from 1990 to 2009). To the best of our knowledge, this is the largest series of PTLD to be reported by a single Institution.
The cases were classified as follows: 70 (58.3%) m-PTLD, 34 (28.3%) p-PTLD, 14 (11.7%) EL, and 2 (1.7%) HL. In the m-PTLD group, 59 were of B-cell origin (52 DLBCL, 4 BL, 2 plasmacytoma-like, 1 multiple myeloma and 1 pleural effusion) and 10 were of T/NK cell lineage (4 peripheral T-cell lymphomas, 2 CTCL, 2 HSTCL, 1 T-ALL and 1 NK-cell lymphoma).
The age of the patients ranged from 1 to 76 years, with 39 pediatric patients (<16 year old) and 81 adult patients. The EBV status of the PTLD, was determined in 94 cases, 58 (61.7%) were positive and 38 (38.3%) were negative, with no difference between pediatric and adult patients (p=0.11). CD 20 positivity was available in 106 specimens and was highly expressed in our series (87.6%) with no differences between adult and pediatric patients (p=0.4). Approximately half of the patients were diagnosed in stage I or II of disease (44.2%), and the other half in advanced stage III or IV (55.8%) with no substantial differences between adults and pediatrics (p=1). ECOG score 0 or 1 was observed in 2/3 of the patients (67.2%), and it was more frequently observed in pediatrics than in adults (respectively 80% and 61%) but the difference was not statistically significant (p=0.06).
Younger age, CD 20 positivity, good ECOG score, platelet and absolute neutrophil count within normal limits correlated with a longer OS (p=0.001, P<0.001, P<0.001, P<0.001 and p=0.003 respectively). PTLD subtype (i.e. EL, pPTLD, mPTLD, HL), gender, decade of diagnosis (1990-1999 vs 2000–2009), organ transplanted, EBV status, anemia, hypoalbuminemia, elevated LDH, extranodal sites involvement, grafted organ involvement, stage at diagnosis did not correlate with the OS in the univariate analysis.
Using the recursive partitioning modeling, a new prognostic score was developed: ECOG score (0-1 vs 2–3), age (pediatrics [<16 year old], adults [>= 16 and <60 year old] and elderly [>60 year old]) and CD 20 status (positive vs negative) provided a tree with 5 nodes (figure 1), separating the patients into 4 risk categories. The low-risk group included pediatric patients with ECOG score of 0–1 (median OS not reached); the intermediate-low-risk group included adults with an ECOG score of 0–1 (median OS of 6.8 years); the intermediate-high-risk group included elderly with ECOG score 0–1 or pediatrics and adults with an ECOG score of 2–4 and CD20 positive or n/a (median OS of 1.8 years); the high-risk group included any patient with an ECOG score of 2–4 and CD20 negative, and elderly patients with CD20 positive or n/a (median OS of 1.3 months).
In addition, in the group of adult patients with DLBCL PTLD and pPTLD (61 total), we analyzed the impact on OS of Rituximab treatment, as single agent or in combination with chemotherapy, compared to chemotherapy or immunosuppressant tapering alone. OS curves of patients treated with and without Rituximab adjusted by ECOG score, are shown in figure 2. The median OS of patients treated without rituximab with ECOG score 0–1 (18 patients) was 10.5 years, with ECOG 2–4 (13 patients) was 1.5 months compared to a median OS of 2.7 years in the rituximab group with ECOG score 0–1 (19 patients), and 1.2 years in the rituximab group with ECOG score 2–4 (11 patients) (p=0.8).
This series proposed a new prognostic model for patients with PTLD, based on ECOG score, age and CD 20 expression. Interestingly, in our series, in a homogeneous population of adult patients with DLBCL and p-PTLD, the use of rituximab as single agent or in combination, compared to chemotherapy and immunosuppression tapering, did not show a survival benefit.

Disclosures:
O'Connor: Allos Therapeutics, Inc.: Research Funding.