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 Blood, 1 February 2005, Vol. 105, No. 3, pp. 994-996.
Prepublished online as a Blood First Edition Paper on October 19, 2004; DOI 10.1182/blood-2004-07-2965.

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CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Brief report

Treatment of primary Epstein-Barr virus infection in patients with X-linked lymphoproliferative disease using B-cell–directed therapy

Michael C. Milone, Donald E. Tsai, Richard L. Hodinka, Lewis B. Silverman, Alejandro Malbran, Mariusz A. Wasik, and Kim E. Nichols

From the Department of Pathology and Laboratory Medicine and the Hematologic Malignancies Program, University of Pennsylvania; the Clinical Virology Laboratory and the Department of Pediatric Oncology, Children's Hospital of Philadelphia; the Departments of Pediatrics and Pathology, University of Pennsylvania School of Medicine, Philadelphia, PA; the Department of Pediatric Oncology, Dana-Farber Cancer Institute; the Department of Pediatric Hematology-Oncology, Children's Hospital, Boston MA; and the Department of Allergy and Immunology, Hospital Britanico, Buenos Aires, Argentina.

X-linked lymphoproliferative disease (XLP) is a congenital immunodeficiency that is characterized by an abnormal immune response to primary Epstein-Barr virus (EBV) infection. After EBV exposure, affected patients often develop fulminant infectious mononucleosis (FIM), a life-threatening condition marked by the uncontrolled expansion and activation of T and B lymphocytes and macrophages. We hypothesized that the rapid elimination of B cells immediately following EBV exposure might reduce the severity of primary EBV infection in patients with XLP. To test this possibility, we administered the anti-CD20 antibody rituximab to 2 patients who presented with acute infection. Following treatment, both patients exhibited a complete resolution of symptoms and no longer demonstrated detectable EBV DNA within circulating lymphocytes. Moreover, neither patient has developed FIM or lymphoma in more than 2 years of follow-up. These data suggest that the pre-emptive use of B-cell–directed therapy may reduce the morbidity and mortality of primary EBV infection in XLP-affected individuals.


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