Expression of CD20 but Not EBV Is Associated with Significantly Improved Overall (OS) and Event Free Survival (EFS) in Children with Post Transplant Lymphoproliferative Disease (PTLD) Following Solid Organ Transplantation (SOT).
Authors: Orjuela Manuela A. , Alobeid Bachir , Liu Xinhua , Siebert Aisha L. , Kott Emily R. , Addonizio Linda J. , Morris Erin , Garvin James H. , Lobritto Steven J. , Cairo Mitchell S. 
Published: April 2020

Abstract
The risk of developing post transplant lymphoproliferative disease (PTLD) following solid organ transplantation (SOT) in children is in large part dependent on the specific organ transplanted and the degree of immune suppression post SOT (Webber et al Lancet 2006; Dharnidharka et al Transplantation 2001; Newell et al Transplantation 1996). However, the importance of expression of CD20 and/or Epstein-Barr virus (EBV) as prognostic factors for development and survival of pediatric PTLD after SOT in young patients are poorly understood. We previously demonstrated the safety and efficacy of cyclophosphamide, prednisone and rituximab (CPR) in CD20+ PTLD (Orjuela/Cairo, CCR 2005). We now report on our experience in children, adolescents and young adults with PTLD following SOT treated at a single institution from 1990–2008 and on the prognostic significance of expression of CD20 and EBV in this population. 45 SOT pts (28 heart, 11 liver, 6 kidney) were diagnosed with PTLD (53.3 % female) at a mean onset of 45±43 months (mo) post primary SOT (4–153). Three patients had multiple SOT. Age at diagnosis of PTLD ranged from14 to 287 mo with mean 118 (SD=77) mo. EBV and CD20 status were evaluated in all evaluable tumor sites. CD20 status was categorized as positive when all tumor sites expressed CD20 (by IHC) and negative when only some or no tumor sites expressed CD20. EBV status was categorized as positive when any tumor sites were EBV positive (by ISH), and negative when no tumor sites were EBV positive. Of 40 evaluable tumors (11 monomorphic, 19 polymorphic, 5 early lesions, 2 T-cell lymphomas, and 3 rarer types (2 HD, 1 multiple myeloma like), 32 (80%) had detectable EBV, while 28 (70%) were classified as CD20 positive. EBV expression was unrelated to age at SOT. Those patients whose PTLD expressed CD20 and/or EBV had shorter time interval between last SOT and the onset of PTLD (CD20 positive vs negative (mean±SD): 28±31 mo vs 64±44 mo, p&lt;0.01, EBV positive vs negative: 29±24 vs 77±59 mos, p&lt;0.02, Wilcoxon test). After controlling for the age at last SOT in the regression model for the time interval between last SOT and PTLD, expression of either CD20 or EBV was significantly associated with the shorter length of the interval. All patients had immunosuppression reduced, followed by chemo-and immunotherapy as needed. Patients with CD20 positive PTLD had a higher 5-year overall and PTLD related EFS than those patients whose PTLD was CD20 negative (92 vs 56%, p=0.02; 84 vs 29%, p&lt;0.001, Chi-square test). The survival curve for EFS differed by CD20 status, log rank test, p&lt;0.01 (Figure one). Organ transplant type and morphology subtype were unrelated to OS or EFS. There was no significant difference in OS or EFS based on EBV expression. In summary, expression of CD20 and/or EBV in young patients with PTLD post SOT are both important predictors of the length of time that elapses between SOT and development of PTLD. CD20 positive PTLD is associated with significantly improved 5-year OS and EFS for PTLD in young SOT patients. Patients with CD20 negative PTLD appear to have lower 5-year survival and EFS suggesting a need for alternative treatment strategies.
Figure Figure