Tumor origin and CD20 expression in posttransplant lymphoproliferative disorder occurring in solid organ transplant recipients: implications for immune-based therapy.
BACKGROUND
Posttransplant lymphoproliferative disorder (PTLD) is a potentially fatal complication of transplantation for which new therapies are being explored, including cytotoxic T-cell infusion and anti-CD20 antibody. Whether the PTLD is of donor cell or recipient cell origin influences the type of cytotoxic T-cell therapy, in view of the MHC-restricted nature of the immune response. The efficacy of anti-CD20 therapy, on the other hand, depends on CD20 expression by neoplastic cells. Only limited prior data exist regarding either of these parameters.


METHODS
Materials for this study were obtained in part from a Southwest Oncology Group clinical trial of solid organ transplant patients with PTLD. Tumor tissue from 21 patients (15 heart, 4 lung, and 2 kidney recipients) was evaluated for donor versus recipient origin by analyzing DNA at multiple polymorphic microsatellites.


RESULTS
Twenty tumors (95%) were of recipient origin. Anatomically separate tumors from a given patient had the same origin. A single PTLD of donor origin arose in donor lung. Epstein-Barr virus (EBV), as assessed by EBER and LMP1 histochemical stains, was present in 16 of 17 tumors. CD20, evaluated immunohistochemically, was expressed diffusely in 12 of 17 tumors and focally in 3 and was undetectable in 2 tumors.


CONCLUSIONS
PTLD after solid organ transplantation is frequently EBV-related and of recipient origin, implying that therapeutic EBV-specific T cells must be matched to the HLA type of the recipient, not that of the donor, in most cases of PTLD. Variable CD20 expression among tumors suggests that in some patients anti-CD20 therapy might be more effective in combination with other therapies.
D015703:Antigens, CD / Q000097:blood; D018951:Antigens, CD20 / Q000097:blood*; D002874:Chromosome Mapping; D020031:Epstein-Barr Virus Infections / Q000209:etiology / Q000276:immunology*; D005500:Follow-Up Studies; D016027:Heart Transplantation / Q000009:adverse effects* / Q000276:immunology / Q000473:pathology; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D007165:Immunosuppression Therapy / Q000009:adverse effects*; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000276:immunology / Q000473:pathology; D016040:Lung Transplantation / Q000009:adverse effects* / Q000276:immunology / Q000473:pathology; D008232:Lymphoproliferative Disorders / Q000209:etiology* / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D018895:Microsatellite Repeats; D009369:Neoplasms / Q000453:epidemiology* / Q000209:etiology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology; D013997:Time Factors
D015703:Antigens, CD; D018951:Antigens, CD20