CD30 expression and survival in posttransplant lymphoproliferative disorders

Abstract

Background: Post-transplant lymphoproliferative disorder (PTLD) is a rare but life-threatening complication of transplantation. For refractory and relapsed PTLD new therapies are needed, such as the antibody-drug conjugate brentuximab vedotin that targets CD30. There is limited knowledge of CD30 expression in various subtypes of PTLD and its correlation to clinicopathological features. Therefore, we studied the expression of CD30 in PTLD following solid organ transplantation and correlated CD30 expression to PTLD subtype, Epstein-Barr virus (EBV)-status, intratumoral regulatory T-cells (Tregs), clinical features, and outcome. Methods: We included 50 cases of PTLD from a nationwide study of PTLDs following solid organ transplantation in Sweden. The tumor biopsies were reevaluated, and clinical data were collected. CD30 expression on tumor cells was analyzed by immunohistochemistry with the clone Ber-H2. Thirtyone cases were stained with clone 236 A/E7 for detection of forkhead box protein 3 (FoxP3, a Treg biomarker). Results: The case series consisted of 6% polymorphic, 88% monomorphic, and 6% Hodgkin lymphoma-like PTLDs and 53% of the cases were EBVþ. Overall, 70% (35/50) of the PTLDs were CD30þ (1% CD30þ tumor cells) and 30% (15/50) were CD30-. All polymorphic PTLDs (n ¼ 3) and Hodgkin lymphomas (n ¼ 3), 88% (14/16) of non-germinal center type of diffuse large B-cell lymphoma (DLBCL), and 75% (9/12) of T-cell PTLDs were CD30þ whereas all germinal center-type of DLBCL (n ¼ 5) and Burkitt type PTLD (n ¼ 2) were CD30-. CD30þ PTLD tended to be EBVþ more frequently (p ¼ .07) and occurred earlier posttransplant (2.1 vs. 8.2 years, p ¼ .01) than CD30-PTLD. Type of transplant and localization of the tumor did not differ between the groups except that CNS engagement was more common in CD30-PTLD (p ¼ .02). CD30-status was not associated with presence of intratumoral Tregs or overall survival. Conclusion: Expression of CD30 varied with PTLD subtype. There was no association between CD30 and survival, regardless of subtype.

Post-Transplant Lymphoproliferative Disorder, Monomorphic Type, in a Kidney Transplant Patient After Administration of Anti-Influenza Vaccine

“…Finally, the role of CD30 in this case is interesting. Although CD30 expression varies in PTLD and is not associated with any specific type, 39 in murine models of influenza vaccination, it has been found that although CD30 is dispensable for the immune response, it plays a role in the persistence of T cells over time. 40 In fact, in monomorphic PTLD of B-cell type, CD30 has been found to be expressed in up to 79% of cases, compared with 38% of CD30 + cases in de novo diffuse large B-cell lymphomas.…”

Anti-CD30 antibody–drug conjugate therapy in lymphoma: current knowledge, remaining controversies, and future perspectives

“…Another CD30-expressing tumor type is post-transplant lymphoproliferative disorder, which is a rare complication of transplantation [104]. Up to 70% of these can be CD30-positive, suggesting a potential role for brentuximab vedotin in the treatment of this disorder [104]. Some CD30-positive B-cell specific lymphomas may also respond to brentuximab vedotin therapy.…”

“…In a phase II trial of brentuximab vedotin in patients with relapsed/refractory EBV-positive CD30-positive mature T, NK, or B-cell lymphoma, ORR was 48%, and at a median of 20 months follow-up, median PFS and OS were 6.2 months and 15.7 months, respectively [ 103 ]. Another CD30-expressing tumor type is post-transplant lymphoproliferative disorder, which is a rare complication of transplantation [ 104 ]. Up to 70% of these can be CD30-positive, suggesting a potential role for brentuximab vedotin in the treatment of this disorder [ 104 ].…”

Recent Advances in Adult Post-Transplant Lymphoproliferative Disorder

“…The anti-CD30 antibody drug conjugate brentuximab vedotin (BV) is currently approved in combination with doxorubicin-based chemotherapy (BV-CHP) as a front-line therapy for CD30+ peripheral T-cell lymphomas (PTCL), after the completion of the phase III pivotal ECHELON-2 trial, where BV-CHP was found to be superior to CHOP. BV is now being investigated in the setting of PTLD, given that there is increasing evidence showing that the CD30+ antigen expression is frequently detected in PTLD [ 108 , 109 , 110 ]. ECHELON-2 excluded immunocompromised patients, given their poor survival outcomes.…”