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)