Cytomegalovirus-associated meningoradiculoneuritis after treatment of mantle cell lymphoma with a combination of chemotherapy and rituximab

Abstract

Rituximab is a chimeric human/mouse monoclonal antibody directed against the CD20 antigen. It has become part of the standard therapy for non-Hodgkin’s lymphoma (NHL). Rituximab effectively kills lymphoma B cells and rapidly leads to the sustained depletion of peripheral blood B cells. Mantle cell lymphoma (MCL) is incurable with standard therapy. The median survival time is short (43 months). Rituximab has been shown to trigger a response in between 20 and 38% of patients with MCL [1]. Sustained rituximab-induced B-cell depletion may compromise the immune system. Accordingly, some viral infections have already been reported in patients with NHL receiving chemotherapy in conjunction with rituximab. Here, we describe an unusual case of cytomegalovirus reactivation in one patient with MCL who had previously been treated with chemotherapy plus rituximab. A57-year-oldmanwasdiagnosedwithcyclinD1-positive inguinal bilateral MCL, Ann Arbor stage II, in March 2003. Before the start of chemotherapy, gammaglobulinemia was normal (10 g/l). He was treated with VAD (vincristine 0.4 mg/day on days 1–4, doxorubicin 9 mg/m/day on days 1–4, dexamethasone 40 mg/day on days 1–4) plus chlorambucil (6 mg/day on days 20–29) and rituximab (375 mg/m on day 28) (5 cycles) for 6 months. This chemotherapy corresponds to the GroupeOuest Est d’etude des Leucemies et Autres Maladies du Sang (GOELAMS) MCL 2001 clinical research protocol, which includes six cycles of VAD– chlorambucil–rituximab followed by therapeutic intensification with total-body irradiation (TBI) plus busulfan before autologous peripheral stem cell reinjection. Before the beginning of the treatment, hypercellularity associated with elevated protein levels in cerebrospinal fluid (CSF) let us suppose neuromeningeal localisation. Thus, intrathecal infusions (nine cycles) with methylprednisolone (40 mg), cytarabine (40mg) and methotrexate (15 mg) were administered. In October 2003, he was referred for accentuated neuromuscular weakness and diffuse chest pain associated with a persistent headache (10 days) resistant to usual painkillers. Clinical examination revealed neurological deficit affecting the psoas territory and the foot and finger elevators. Osteotendinous reflexeswere abolished.Nopulmonary, cardiac or abdominal manifestations were observed. Whole-body computed tomography (CT) found an interstitial syndrome without adenopathy. Electromyography and nerve conduction analysis did not find any acute signs but revealed chronic anterior horn cell lesions. Bone marrow aspirate was normal. Peripheral blood contained atypical basophilic lymphocytes, suggestive of lymphocyte activation. C-reactive protein concentration was moderately elevated (33 g/l). Hypogammaglobulinemia (5 g/l) without monoclonal secretion was found. Blood and bone marrow were negative for cyclin D1. Fluorescent in situ hybridisation (FISH) analysis failed to detect t(11;14) translocation in the CSF. Hepatic and kidney functions were normal. Blood cultures were negative for bacteria. Serum was positive for cytomegalovirus (CMV) IgG with a high avidity, showing prior immunity. Electroencephalography (EEG) showed a focal lesion in the frontal and temporal regions, but no associated clinical phenotype was observed. CSF contained an abnormally high amount of protein (0.63 g/l) and normal glucose and chloride levels. The CSF contained 38 leukocytes/mm (65% lymphocytes, 9% monocytes and 25% polynuclear S. Vallet (*) . A. Tran . M. C. Legrand-Quillien . V. Narbonne Department of Microbiology (E.A. Biodiversity and Microbial Ecology no. 3882), University Hospital Morvan, 2 avenue Foch, 29609 Brest Cedex, France e-mail: sophie.vallet@chu-brest.fr Tel.: +33-2-98223308 Fax: +33-2-98223987