Pediatric post-transplant lymphoproliferative disorder after cardiac transplantation

Abstract

Post-transplant lymphoproliferative disorder (PTLD) is a well recognized and potentially fatal complication after pediatric cardiac transplantation. PTLD encompasses a wide spectrum, ranging from benign hyperplasia to more aggressive lymphoma. Most cases are Epstein-Barr virus (EBV)-related B-cell tumors resulting from impaired immunity due to immunosuppressive therapy. Pediatric recipients, often seronegative for EBV at transplantation, have a greater risk for PTLD than adults. The clinical presentation of PTLD varies from isolated lymphadenopathy to systemic disease; common sites involved are gastrointestinal tract, lung or airway, and cervical lesions. Timely and accurate diagnosis based on histological examination of biopsy tissue is essential for early intervention. Immunostaining for EBV and evaluation for clonality are needed. For prophylaxis when EBV viral loads are increasing or for initial treatment of early lesions or polymorphic PTLD, a reduction in immunosuppressive treatment is a key component of therapy, but caution is needed for possible rebound allograft rejection. Chemotherapy is indicated for patients with poor response to reduced immunosuppression and for highly aggressive monomorphic PTLD. The use of rituximab in combination with chemotherapy is effective. For the time being, avoiding excessive immunosuppression is the most effective strategy for reducing the incidence of PTLD. Calcineurin inhibitor (CNI) minimization with proliferation signal inhibitors (PSIs) or conversion from a CNI to a PSI might be useful for preventing both development of PTLD and allograft rejection.

Using Epstein-Barr Viral Load Assays To Diagnose, Monitor, and Prevent Posttransplant Lymphoproliferative Disorder

“…Complementary interventions include infusing donor lymphocytes (typical healthy donor mononuclear cells are comprised of about 5% EBV-directed cells) (17), infusing EBV-specific cytotoxic T cells that are grown ex vivo by exposing HLA-matched T cells to EBV antigens (37,64,79,85,168), and infusing anti-CD20 monoclonal antibody (e.g., rituximab) (33,60,71,72,171,197). If initial intervention is insufficient, more traditional cancer treatment with radiation and multidrug chemotherapy is used (135,190).…”

Usefulness and Limitations of Rituximab in Managing Patients With Lymphoproliferative Disorder After Heart Transplantation

“…[29][30][31][32][33][34][35][36][37] Treatment options for PTLD after heart transplant are not standardized, usually sequential, starting with a reduction in immunosuppression. In a prospective study including 13 heart transplant patients, aggressive reduction in immuno suppression (calcineurin reduction by 50% for 2 weeks and further 50% reduction for 1 week if not in complete remission), produced noncomplete remission and rejection was frequent.…”

Lymphoproliferative Disorders After Solid Organ Transplantation—Classification, Incidence, Risk Factors, Early Detection and Treatment Options

“…The antibody is generally well tolerated and rapidly induces the depletion of mature B-lymphocytes, reducing the compartment of EBVinfected cells, with an associated normalization of the viral load [50,80]. Initial results with rituximab combined with reduced immunosuppression or low dose chemotherapy (in a synchronous or sequential manner) have been promising [17,[81][82][83].…”

“…Vaccination may be performed using the gp350 virus membrane protein; this vaccine triggered a favorable immune response in healthy volunteers. However, the issue of EBV vaccination in transplantation is still controversial [17,80,104,105].…”

“…Immunosuppressants inhibiting cell proliferation seem to be most suitable for this task. Rapamycin and its analogs have been proven to inhibit lymphoma proliferation via mTOR kinase inhibition, and can be recommended for maintenance immunosuppressive therapy in transplanted patients treated for PTLD [17,48,80,106]. Initial data suggests that conversion to rapamycin as an immunosuppressant has a favorable effect in kidney transplanted patients with PTLD [48,107].…”