Abstract
Castleman’s disease (CD) is a rare, non-clonal lymphoproliferative disorder featuring histologically hyaline-vascular (HV), plasmacytic (PC) or a mixed variant. Clinically, CD presents with localized lymphadenopathy (unicentric CD: UCD) or generalized lymphadenopathy often associated with constitutional symptoms (multicentric CD: MCD). The etiology of CD in HIV negative patients is not known, but elevated serum levels of IL6 are closely linked to the gravity of systemic manifestations of MCD. We present data on the largest CD series thus far reported with various treatment modalities, including anti-IL6 strategies. Between 1989 and 2004, 37 patients were referred to our institution with HIV-negative CD. None of the patients tested had evidence of HHV8 infection by serology or PCR. Eleven patients had UCD. The median age in UCD was 43 years (range 29–62) with a preponderance of non-white patients (ratio 4.5:1). All patients had HV disease except one who had PC variant. One patient did not receive any specific treatment and is lost to follow up. The other 10 patients all underwent complete surgical resection. Three patients were de-bulked prior to surgery with steroids, rituxan ±cytoxan (n=2) or radiotherapy (n=1). None of these patients has evidence of disease with a median follow up of 43 mths (range 12–140 mths). Twenty-six patients had MCD. The median age was 44 years (range: 19–87) with no racial preponderance. All presented with constitutional symptoms including fatigue, anorexia or low grade fever. MCD was equal distributed amongst histological types (HV versus PC/mixed disease) and was frequently associated with peripheral neuropathy (n=5). Bronchiolitis obliterans and pemphigus, amyloidosis and myeloma were each present in 1 respective patient. The OS in MCD was 8.8 yrs with no significant difference between HVD and PC/mixed variants. A group of 12 MCD patients was treated with steroids, chemotherapy and/or anti-CD20 ab had an OS of 42 months (range: 2–111). Four patients died, whilst 4 are alive and disease free at 48, 50, 96 and 111 months. A group of 5 MCD patients was treated with the anti-trypazonomiasis agent suramin, which has anti-IL6 properties, and 4 died. The fifth patient is a long-term survivor (108 mths) after rescue with anti-IL6 based ab therapy. Nine additional MCD patients received anti-IL6 based ab therapy; 2 died. The median OS survival in this group was 74 months (range: 10–168) with 4 patients in CR at 16, 84, 108 and 168 mths. Anti-IL6 based ab therapy was very effective in abrogating debilitating constitutional symptoms. In recent patients, FDG-PET scanning showed that involved lymph nodes visible by CT scan had differential metabolic activity. PET showed response to therapy earlier than on CT or could demonstrate residual activity in normal nodes. We conclude that 1) MCD often has HV type histology, 2) anti-IL6 based ab therapies hold considerable promise in the management of symptomatic MCD, and 3) PET-scanning is helpful in monitoring disease response and activity.
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