The absence of CD20 messenger RNA in recurrent cutaneous B‐cell lymphoma following rituximab therapy

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Abstract
Background:  Rituximab has been used to treat relapsed low‐grade or advanced non‐Hodgkin's lymphoma since 1997, targeting the CD20 antigen expressed by B cells. Single‐agent rituximab therapy is safe and well tolerated. Recurrences showing a loss of CD20 expression following rituximab therapy have been reported.Methods:  Four patients with CD20‐positive cutaneous B‐cell lymphoma received rituximab therapy with subsequent recurrences. The biopsies were assessed for cytoplasmic CD20 expression; CD20 messenger RNA was also assessed where tissue was available.Results:  Cutaneous relapses occurring within 1.5–3 months following the last dose of rituximab were CD20 negative. In three cases, subsequent relapses showed renewed expression of CD20. Those biopsies demonstrating a loss of surface and cytoplasmic CD20 by immunohistochemistry also showed no evidence of messenger RNA for CD20 using an in situ polymerase chain reaction‐based methodology.Conclusions:  Rituximab may be associated with the emergence of CD20‐negative B‐cell clones, potentially rendering a tumor insensitive to this drug. Conversely, following cessation of the drug, a re‐expression of CD20 within the neoplastic cells may occur allowing therapeutic intervention with this monoclonal antibody. The loss of CD20 expression appears to be a direct effect of the drug on CD20 messenger RNA synthesis.

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