Epstein–Barr virus-associated post-transplant lymphoproliferative disease with central nervous system involvement after unrelated allogeneic hematopoietic stem cell transplantation

Abstract

Post-transplant lymphoproliferative disorders (PTLD) represent an heterogeneous group of abnormal lymphoid proliferation related to Epstein-Barr virus (EBV) reactivation that arise early after allogeneic hematopoietic stem cell transplant (HSCT). PLTD with central nervous system (CNS) involvement has been reported in few cases. We describe the case of a 31-year-old-man who developed an EBV-related PTLD with CNS involvement 2 months after an allogeneic unrelated HSCT for acute myeloid leukemia in first complete remission who was successfully treated with rituximab, cidofovir and intrathecal infusion of methotrexate and methylprednisolone.

Management of HSV, VZV and EBV infections in patients with hematological malignancies and after SCT: guidelines from the Second European Conference on Infections in Leukemia

“…The following first-line treatment of PTLD is recommended: (i) anti-CD20 therapy (rituximab) (AII); 151,[171][172][173] (ii) reduction of immunosuppressive therapy, if possible (BII); (iii) adoptive immunotherapy with in vitro-generated donor EBVcytotoxic T-cells, if available (CII); 168,174 and (iv) infusion of donor lymphocytes (DLI) to restore T-cell reactivity (CIII). Generally recommended both for preemptive and symptomatic therapy is the use of anti-CD20 MoAbs, in spite of lack of randomized trials.…”

Epstein–Barr virus-associated leukemic lymphoma after allogeneic stem cell transplantation

“…Because monotherapy with rituximab is reported to rescue 63% patients with PTLD 14 , we expected that rituximab therapy would not be able to cure a fulminant EBV-PTLD as seen in our case even in combination with DLI. Cidofovir, a monophosphate nucleotide analogue of cytosine that inhibits viral DNA polymerase, is effective in treating various kinds of viral infections due to adenovirus 15 , BK virus 16 , and EBV [17][18][19] . Although the addition of cidofovir to rituximab-DLI therapy may have helped the patient to overcome such a disastrous condition without obvious adverse effects, there is little evidence to suggest therapeutic efficacy against EBV 14,20 .…”

Central nervous system post-transplant lymphoproliferative disorder despite negative serum and spinal fluid Epstein–Barr virus DNA PCR

“…Rituximab has shown promising activity in systemic PTLD, but Pakakasama et al 6 reported no response of primary CNS PTLD to rituximab therapy, suggesting that CNS penetration might be poor. In contrast, Nozzoli et al 4 reported complete response of CNS PTLD with intravenous rituximab, cidofovir and intrathecal methotrexate and methylprednisolone in a patient with leptomeningeal disease without focal brain lesions. It is not clear whether the same response could be obtained with rituximab alone.…”

“…Donor lymphocyte infusion carries the risk of causing GVHD and has not been shown to be effective in CNS PTLD. 4 Pakakasama et al 6 reported favorable response of CNS PTLD to a combination of EBV-specific cytotoxic T cells (EBV-CTL) with hydroxyurea. EBV-CTLs are, however, not widely available and can take months to generate.…”

“…3 Isolated CNS involvement with PTLD after HSCT is exceedingly rare with only four reports in the medical literature. [4][5][6][7] Monitoring of serum EBV viral loads by quantitative PCR has been shown to correlate with the development of EBV-associated PTLD. Van Esser et al 8 showed that plasma EBV DNA PCR not only quantitatively predicted the development of EBV-associated PTLD but a viral load of o1000 genome equivalents/ml had a negative predictive value of 100% in T-cell-depleted HSCT patients.…”