Primary central nervous system post‐transplantation lymphoproliferative disorder

Abstract

BACKGROUND Primary central nervous system (CNS) post-transplantation lymphoproliferative disorder (PCNS-PTLD) is a rare complication of solid organ transplantation. The objectives of this study were to define the clinical, radiologic, and pathologic features of this disease and to explore the impact of treatment on patient outcomes. METHODS The authors reviewed the databases of participating institutions of the International Primary CNS Lymphoma Collaborative Group for cases of PCNS-PTLD. Thirty-four patients who had pathologically confirmed PCNS-PTLD without evidence of systemic PTLD were investigated retrospectively. RESULTS The median time from transplantation to diagnosis of PCNS-PTLD was 4.4 years. Disease usually was multifocal and involved any location of the brain but was most common in the cerebral hemispheres, usually in the subcortical white matter or basal ganglia. Radiographically, all lesions enhanced either homogenously or in a ring-enhancing pattern. Cerebral biopsy was required to establish diagnosis in most patients. Most patients had monomorphic, Epstein-Barr virus (EBV)-positive disease of B-cell origin. Response rates were high regardless of treatment type, and the median survival was 47 months. Age was the only factor predictive of survival. CONCLUSIONS The current study demonstrated that PCNS-PTLD is typically an EBV-induced B-cell lymphoma that is responsive to treatment with favorable survival in many patients. An aggressive approach to tissue confirmation of diagnosis and treatment with chemotherapy or radiotherapy should be strongly considered.

Complete and Durable Responses in Primary Central Nervous System Posttransplant Lymphoproliferative Disorder with Zidovudine, Ganciclovir, Rituximab, and Dexamethasone

“…The median OS was 17 months. In another retrospective review by Cavaliere and colleagues 11 spanning 25 years, 34 patients with PCNS-PTLD received systemic therapy (temozolamide, HD-MTX alone or in combination with other systemic chemotherapy, or CHOP), intrathecal chemotherapy, immunotherapy (rituximab), and radiation therapy. The authors report a 47-month median survival with all treatment outcomes combined.…”

“…PCNS-PTLD is a rare complication encountered in patients receiving iatrogenic immunosuppression after solid organ transplantation (SOT) and portends a poor prognosis with estimated three-year survival rates between 32–38% in multi-center retrospective analyses 11–13 . For decades, the standard treatment of care has included whole brain radiotherapy (WBRT) and methotrexate-based chemotherapy, treatments which lead to severe neurotoxicity, mucositis, myelosuppression, and leukoencephalopathy 11–13 .…”

“…For decades, the standard treatment of care has included whole brain radiotherapy (WBRT) and methotrexate-based chemotherapy, treatments which lead to severe neurotoxicity, mucositis, myelosuppression, and leukoencephalopathy 11–13 . Given poor survival, prohibitive treatment toxicity, and an increasing incidence of PCNS-PTLD, better therapies are needed 14 .…”

Management of posttransplant lymphoproliferative disorders following solid organ transplant: an update

“…In the case of primary central nervous system PTLD, radiotherapy might be superior to other types of therapy [79,80], although chemotherapy and rituximab might be useful as well [80].…”

Posttransplant Lymphoproliferative Disorders Following Kidney Transplantation

“…71,99,112,113 In primary central nervous system (PCNSL) PTLD, radiotherapy and chemotherapy may both lead to a high response rate. 72,114,115 Although rituximab hardly crosses the blood-brain-barrier (BBB), case reports have shown promising results with the use of systemic rituximab in the treatment of PCNSL-PTLD, probably due to disruption of the BBB in patients presenting with central nervous system malignancies. However, the exact value of systemic or intrathecal rituximab needs to be determined taking into consideration the fact that in most cases anti-CD20 therapy was combined with other treatments.…”