JC papovavirus leukoencephalopathy after first line treatment with CHOP and rituximab

Abstract

Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating infection of the central nervous system caused by the JC papovavirus usually seen among immunocompromised patients. PML arises upon JC virus reactivation during periods of immunosuppression. PML may be seen among patients with lymphoproliferative disorders and immunosuppression induced by chemotherapy.1 Recently, an association between PML and rituximab in the setting of autologous 2, 3 or allogeneic 4 transplantation has been suggested. We report the first case of a woman with a non Hodgkin lymphoma (NHL) who developed PML after a combination of rituximab with chemotherapy as first line treatment.A 67-year-old woman suffered from a mantle cell lymphoma diagnosed on splenomegaly and hyperlymphocytosis. Staging showed a stage IV with bone marrow involvement. The patient was treated with a combination of rituximab (375 mg . Cerebral magnetic resonance imaging performed three months after the diagnosis showed an increase of the leukoencephalopathy lesions. The patient deceased six months after the beginning of symptoms.Rare cases of PML have been reported among patients with lymphoma. A recent survey retrospectively analyzed 46 cases of PML occurring during lymphoproliferative diseases. 1 The implication of rituximab in these cases, without transplantation setting, has not been highlighted. Moreover, the patients reported were often in relapse, and were heavily pre treated. 1Four cases of PML were recently described in patients who were treated with chemotherapy, transplantation (autologous for three and allogeneic for one) and peritransplantation rituximab.2-4 Despite these cases, a direct association between rituximab and PML remains moreover speculative. The addition of peritransplantation rituximab which results in delayed T-cell reconstitution after transplantation may be involved in the occurrence for late infectious diseases.In our case, the link between rituximab treatment and PML development appears disputable, mostly because the patient showed at the same time a severe suppression of T cell immunity (110 CD4 + T cells/∝L). Interestingly, another case of PML was recently reported in a patient treated with rituximab without transplantation. 5The patient was 62 year-old with chronic lymphocytic leukemia for 14 years and Richter transformation for 2. He was heavily pre treated (chlorambucil, fludarabine) although PML developed 14 months after 6 courses of rituximab with chemotherapy.Our patient is, to our knowledge, the first case of PML after a combination of CHOP with rituximab, in first induction procedure. Although the contributory role of rituximab remains speculative, our additional case highlights the need for an accurate surveillance, even in patients not heavily pre treated, as in first induction procedure with CHOP and rituximab.

Remission of steroid-resistant nephrotic syndrome due to focal and segmental glomerulosclerosis using rituximab

“…The dose of rituximab presently used in the treatment of nephrotic syndrome (four weekly infusions at 375 mg/m 2 /dose) is based on B-cell lymphoma studies [18]. Side effects of the drug include fevers, chills, rigors, orthostatic hypotension, anaphylaxis, bronchospasm, cardiac toxicity, human anti-chimeric antibodies, and JC polyoma virus induced progressive multifocal leucoencephalopathy [19][20][21]. To date, there are four case reports found in the literature on rituximab use in the treatment of primary nephrotic syndrome in pediatric patients with native kidney disease [10][11][12][13].…”

Progressive multifocal leukoencephalopathy after rituximab therapy in HIV-negative patients: a report of 57 cases from the Research on Adverse Drug Events and Reports project

“…[18][19][20][21][22][23][24][25][26][27][28][29][30][31] The search covered the period from 1997, the date of the first FDA approval granted for rituximab, to December 31, 2008. Duplicate reports were identified based on age, sex, and underlying illness.…”

Viral infections in paediatric patients receiving conventional cancer chemotherapy

“…Particularly in patients with additional immunosuppression, reactivation of viral infection (CMV, VZV, HCV,156 HBV,157 – 159 B19,106 EV160 and JC virus161 162) has been observed after rituximab treatment 163. The paediatric population requiring this treatment is small, and rarely occurring adverse effects must not be considered a contraindication.…”