Central nervous system dissemination in immunocompetent patients with aggressive lymphomas: incidence, risk factors and therapeutic options.
Central nervous system (CNS) dissemination is a rare (4-5%) but usually fatal complication of aggressive lymphomas. Prophylaxis modalities to prevent CNS dissemination in aggressive lymphomas cannot be widely applied to every lymphoma patient since it is associated with increased risk of neurotoxicity. Therefore, identification of high-risk patients as the best candidates to receive CNS prophylaxis constitutes a major endpoint in the management of these malignancies. Various risk factors and models for CNS recurrence have been described. Parameters reflecting the extent and proliferation of the disease, like elevated serum lactate dehydrogenase levels, involvement of multiple extranodal sites, advanced stage and high age-adjusted International Prognostic Index (IPI) score, as well as the involvement of specific anatomic sites, like testes, orbit, paranasal sinuses, have been identified and confirmed as important to predict CNS dissemination. Management of this complication in aggressive lymphomas with conventional-dose chemotherapy is associated with disappointing results, while some preliminary but encouraging experiences suggest a potential role of high-dose chemotherapy and stem cell transplantation. The analysis of recent clinical studies could lead to advancement in the prognosis of aggressive lymphomas, but several questions regarding the optimum chemotherapy combination, the best conditioning regimen and the role of radiation therapy and intrathecal chemotherapy remain still unanswered. The purposes of the present review are to critically analyse current data on the risk of CNS dissemination in aggressive lymphomas, the clinical presentation of secondary CNS lymphomas and the efficacy of CNS prophylaxis as well as to discuss the available therapeutic options for this devastating event.
Ferreri
Andrés J M
AJ
Unit of Lymphoid Malignancies, Department of Oncology, San Raffaele H Scientific Institute, Milan, Italy. andres.ferreri@hsr.it
Assanelli
Andrea
A
Crocchiolo
Roberto
R
Ciceri
Fabio
F
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D016543:Central Nervous System Neoplasms / Q000175:diagnosis / Q000453:epidemiology / Q000556:secondary* / Q000628:therapy; D002555:Cerebrospinal Fluid / Q000737:chemistry / Q000166:cytology; D003131:Combined Modality Therapy; D016371:Cranial Irradiation; D003952:Diagnostic Imaging / Q000379:methods; D018450:Disease Progression; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015994:Incidence; D007278:Injections, Spinal; D008223:Lymphoma / Q000453:epidemiology / Q000473:pathology* / Q000532:radiotherapy / Q000628:therapy; D015337:Multicenter Studies as Topic / Q000706:statistics & numerical data; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data; D012307:Risk Factors; D000069283:Rituximab
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab