Pathologic and Clinical Features Of CD30+ Post-Transplant Lymphoproliferative Disorders: A Large Retrospective Single Institutional Study

Abstract Introduction B-cell post-transplant lymphoproliferative disorders (B-PTLD) represent a spectrum of lymphoid neoplasms arising as a consequence of impaired T-cell surveillance secondary to immunosuppressive medications. Epstein-Barr Virus (EBV) has been implicated in the development of B-PTLD. B-PTLDs diagnosed within one year post-transplant are more likely to be associated with EBV whereas B-PTLD diagnosed after a year are more likely to be EBV-negative and are associated with worse prognosis. Studies have shown that EBV up-regulates CD30 expression, a member of the TNF-receptor superfamily (Haque et al 2011). Novel agents are now available that target cells expressing CD30. Hence, knowledge of the expression profiles and the clinical characteristics of CD30+ neoplasms is warranted. In this study, we evaluated CD30 expression in 59 cases of B-PTLD and correlated CD30 and EBV status with clinical characteristics. Methods Consecutive cases of B-PTLD diagnosed between 1997 and 2013 were retrieved from our archives. Immunohistochemistry (ISH) for CD30 was performed on formalin-fixed, paraffin embedded biopsies using the BerH2 monoclonal antibody (BioSB, Santa Barbara, CA) according to standard methods. Positive expression was pre-defined as CD30 expression by ≥20% of the lesional cells (Figure 1). Log-rank and Fischer's Exact 2-sided Test were performed in STATA 11, as appropriate. Results The 59 B-PTLDs occurred in 54 patients. Three patients had two different sites biopsied during the diagnostic workup. Two other patients had recurrent B-PTLD. The median age at diagnosis was 22.8 years old (range 1.2 to 75.9 years); 65% were male. The median time from transplant to diagnosis was 2.6 years (range 6 weeks to 15.9 years, mean 4.2 years). Eighteen cases (35%) were diagnosed within the first year of transplantation. The organs transplanted are detailed in Table 1 with the percentage of CD30+ cases noted. Prior to transplantation, only 25/44 (57%) patients were EBV IgG seropositive, likely reflecting the number of children who were younger than age ten when transplanted (21/52; 40%). (Orjuela et al 2011). Serum EBV Polymerase Chain Reaction (PCR) was positive in 18/27 (67%) cases analyzed. Table 1 . Organ Transplanted n Percentage CD30+ Kidney 15 60% Heart 22 63% Lung 3 100% Heart-Lung 1 100% Liver 10 60% Pancreas 1 0% Small Bowel 1 100% Bone Marrow 1 100% Pathological data are summarized in Table 2. In total, 39 of 59 cases (66%) showed 20% or more CD30 expression. Positive EBV ISH was significantly associated with CD30 expression (r=0.38, p Table 2 . Histology CD 30 Positive CD 20 Positive EBER Positive Polymorphic (n=25) 22/ 25 = 88% 19/25= 76% 22/25 = 88% Monomorphic: DLBCL (n=23) 12/23 = 52% 19/23 = 83% 14/23 = 61% Monomorphic: Burkitt Lymphoma (n=3) 1/3 = 33% 3/3 = 100% 1/3 = 33% Monomorphic:Plasmacytoma-like (n=8) 4/8 = 50% 4/8 = 50% 4/8 = 50% Conclusion We observed a high frequency of CD30 expression in patients with B-PTLD. Expression of CD30 correlates with ISH evidence of EBV infection in B-PTLD. In addition, positive serum EBV PCR was associated with CD30 expression. These two findings further support the link between EBV infection and CD30 expression. CD30 positivity was still found in 39% of EBER – negative cases, suggesting that CD30 ISH should be considered on all cases of B-PTLD. A monoclonal antibody conjugated to the cytotoxic agent MMAE,Brentuximab Vedotin (SGN-35), has shown activity in clinical trials against CD30 positive lymphomas (Jacobson et al 2012). Considering the relatively common prevalence of CD30+ expression in PTLD, brentuximab vedotin could be considered for study in combination with traditional front-line therapies or as an alternative therapy for relapsed/refractory disease. A prospective clinical trial (NCT 01805037) at Northwestern University is ongoing. Disclosures: Schecter: Seattle Genetics: Research Funding, Speakers Bureau. O'Connor: Seattle Genetics: Research Funding.