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Blood, Vol. 95 No. 1 (January 1), 2000:
pp. 56-61
Improvement in Castleman's disease by humanized
anti-interleukin-6 receptor antibody therapy
Norihiro Nishimoto,
Mitsuko Sasai,
Yoshihito Shima,
Masashi Nakagawa,
Tomoshige Matsumoto,
Toshikazu Shirai,
Tadamitsu Kishimoto, and
Kazuyuki Yoshizaki
From the Department of Medical Science I, School of Health and Sport
Sciences, Osaka University, Suita-city, Osaka, Japan; Department of
Medicine III, Osaka University Medical School, Suita-city, Osaka,
Japan; Department of Pathology II, Juntendo University School of
Medicine, Tokyo, Japan.
Castleman's disease, an atypical lymphoproliferative disorder, can
be classified into 2 types: hyaline-vascular and plasma cell types
according to the histologic features of the affected lymph nodes. The
plasma cell type is frequently associated with systemic manifestations
and is often refractory to systemic therapy including corticosteroids
and chemotherapy, particularly in multicentric form. Dysregulated
overproduction of interleukin-6 (IL-6) from affected lymph nodes is
thought to be responsible for the systemic manifestations of this
disease. Therefore, interference with IL-6 signal transduction may
constitute a new therapeutic strategy for this disease. We used
humanized anti-IL-6 receptor antibody (rhPM-1) to treat 7 patients with
multicentric plasma cell or mixed type Castleman's disease. All
patients had systemic manifestations including secondary amyloidosis in
3. With the approval of our institution's ethics committee and the
consent of the patients, they were treated with 50 to 100 mg
rhPM-1 either once or twice weekly. Immediately after
administration of rhPM-1, fever and fatigue disappeared, and anemia as
well as serum levels of C-reactive protein (CRP), fibrinogen, and
albumin started to improve. After 3 months of treatment,
hypergammaglobulinemia and lymphadenopathy were remarkably alleviated,
as were renal function abnormalities in patients with amyloidosis.
Treatment was well tolerated with only transient leukopenia.
Histopathologic examination revealed reduced follicular
hyperplasia and vascularity after rhPM-1 treatment. The
pathophysiologic significance of IL-6 in Castleman's disease was thus
confirmed, and blockade of the IL-6 signal by rhPM-1 is thought
to have potential as a new therapy based on the pathophysiologic mechanism of multicentric Castleman's disease. (Blood.
2000;95:56-61)
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