Correspondence
Fatal Reactivation of Cytomegalovirus Infection after Use of Rituximab for a Post-Transplantation Lymphoproliferative Disorder
N Engl J Med 2001; 345:1000September 27, 2001
- Article
To the Editor:
Rituximab is a chimeric monoclonal antibody directed against the CD20 antigen expressed on most B cells and is used to treat B-cell non-Hodgkin's lymphoma.1 Recently, rituximab has been used to treat post-transplantation lymphoproliferative disorders, which may occur after solid-organ and bone marrow transplantation; the prognosis associated with these disorders is usually poor, even if the doses of immunosuppressive drugs are reduced. Rituximab induces profound and durable B-cell depletion without a substantial decrease in serum immunoglobulin levels. Viral infection has rarely been reported after the use of this agent. Hepatitis B reactivation,1,2 visceral varicella–zoster infection,3 and pure red-cell aplasia due to chronic parvovirus B19 infection4 have occurred in patients treated with rituximab, but in all these cases, rituximab was combined with chemotherapy. We describe a fatal reactivation of cytomegalovirus infection after rituximab therapy in a patient with a post-transplantation lymphoproliferative disorder.
A 64-year-old woman underwent a kidney transplantation in 1990. Both the donor and the recipient were positive for cytomegalovirus. The subsequent immunosuppressive regimen included cyclosporine at a dose of 140 mg per day and prednisone at a dose of 10 mg per day. In July 2000, left cervical adenopathy and multiple cutaneous lesions developed. Cutaneous and nodal post-transplantation lymphoma was diagnosed. After the administration of cyclosporine was discontinued and the dose of prednisone was temporarily increased, the patient had a partial response, and the dose of prednisone was tapered to 10 mg per day. She then received four weekly courses of rituximab (dose, 375 mg per square meter of body-surface area per course), with a good clinical response. However, after completion of the fourth course in December 2000, bilateral interstitial infiltrates developed, and blood cultures were found to be strongly positive for cytomegalovirus. Despite treatment with ganciclovir, the patient died.
Cytomegalovirus infection is the most frequent viral infection after solid-organ transplantation. It usually occurs during the first weeks or months after transplantation. The occurrence of disseminated cytomegalovirus infection 10 years after a kidney transplantation is unusual, especially 3 months after a reduction in immunosuppressive therapy. The fact that cytomegalovirus reactivation occurred after rituximab treatment but in the absence of chemotherapy is particularly striking, because rituximab has been considered to impair humoral immunity, which does not play a key part in defending against cytomegalovirus infection. As recently suggested for hepatitis B infection,2 before immunosuppressed patients begin rituximab therapy, it should be determined whether they are infected with cytomegalovirus.
4 ReferencesFlorence Suzan, M.D.
Institut Gustave Roussy, 94805 Villejuif, FranceMounia Ammor, M.D.
Hôpital du Kremlin-Bicêtre, 94270 Le Kremlin-Bicêtre, FranceVincent Ribrag, M.D.
Institut Gustave Roussy, 94805 Villejuif, France
ribrag@igr.fr 1
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Dervite I ,Hober D ,Morel P . Acute hepatitis B in a patient with antibodies to hepatitis B surface antigen who was receiving rituximab. N Engl J Med 2001;344:68-69
Full Text | Web of Science | Medline3
Bermudez A ,Marco F ,Conde E ,Mazo E ,Recio M ,Zubizarreta A . Fatal visceral varicella-zoster infection following rituximab and chemotherapy treatment in a patient with follicular lymphoma. Haematologica 2000;85:894-895
Web of Science | Medline4
Sharma VR ,Fleming DR ,Slone SP . Pure red cell aplasia due to parvovirus B19 in a patient treated with rituximab. Blood 2000;96:1184-1186
Web of Science | Medline
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