Successful treatment of Castleman's disease with interleukin-1 receptor antagonist (Anakinra)

Abstract

Castleman's disease (CD) is a very rare lymphoproliferative disorder whose underlying pathophysiology is not fully understood and for which no standard treatment exists. Because interleukin-1 (IL-1) might promote the production of interleukin-6 (IL-6), a key pathogenic factor for the disease, we hypothesized that blocking the interleukin-1 receptor would be a useful therapy for CD. We report the case of a 61-year-old woman with CD who had undergone multiple treatments, including cladribine, rituximab, steroids, etanercept, and anti-IL-6 monoclonal antibody, and whose disease was refractory to all of these treatments. She was started on the recombinant IL-1 receptor antagonist, Anakinra, at a subcutaneous dose of 100 mg daily. Within one week, her fatigue and anorexia markedly improved, and her laboratory abnormalities, including anemia, thrombocytosis, leukocytosis, and elevated markers of inflammation, all resolved. Our observation suggests that Anakinra may be an attractive therapeutic approach for refractory multicentric CD.

Figure 1

Representative blood cell counts prior to and after treatment with Anakinra. Hemoglobin (A), white blood cell count (B), and platelet count (C) improved after initiation of Anakinra. Arrow indicates when treatment with Anakinra was begun. Note: Initial drop in counts in 2005 corresponded with initiation of anti-IL-6 treatment. Also, patient underwent repeat plateletpheresis when platelet counts became elevated to more than 1,000 × 10 ⁹/L.

Figure 2

Whole-body ¹⁸FDG PET scan done immediately before (A), and 3 months (B), and 7 months (C) after treatment with Anakinra. Increased FDG uptake throughout the bone marrow is markedly less prominent after 3 and 7 months of treatment with Anakinra.