Natural History of KSHV-Associated Multicentric Castleman s Disease

Background:

• Multicentric Castleman s disease (MCD) is a rare but lethal Kaposi s sarcoma-associated herpesvirus (KSHV) associated lymphoproliferative disorder with a historical median survival of 2 years. It occurs more often in HIV-infected individuals than those without HIV infection. The poor prognosis is not fully explained by the underlying HIV, as the HIV-negative cases appear to have little or no survival advantage over the HIV-positive cohort. The disease has no defined standard treatment and there is much to be learned about its pathogenesis and natural history with current treatments.
• Patients with KSHV-MCD may present with other KSHV-associated conditions such as Kaposi sarcoma (KS) and may develop primary effusion lymphoma (PEL) following their diagnosis, which may affect morbidity and mortality. It is not clear how these concurrent conditions develop simultaneously and over time.
• Since 2004, the HIV and AIDS Malignancy Branch (HAMB) has studied the natural history and assessed novel therapies for KSHV-MCD which has contributed to the development of at least two therapies that are now considered as first-line therapies: (1) rituximab plus liposomal doxorubicin and (2) high dose zidovudine plus valganciclovir.
• These therapies plus either rituximab alone or other rituximab-based therapies that have been developed over the last 15 years have resulted in durable responses in patients with KSHV-MCD and have substantially improved the prognosis of these patients.
• The longitudinal evaluations along with tissue sample collection, imaging studies, and participant reported outcomes will allow for the development of a better understanding of the natural history of this disease, and the development of the basis for more effective treatments.

Objective:

-To study and describe the natural history of KSHV-MCD

Eligibility:

• Age >= 18 years
• Biopsy proven KSHV-associated MCD

Design:

• This will be a long-term study to comprehensively study participants with KSHV-MCD
• Medical history will be collected, and participants followed throughout the course of their illness, with particular attention to patterns of disease presentation, recurrence and progression, response to therapies, and duration of responses
• Tissue samples and blood will be obtained from participants during this study.
• We anticipate accruing 135 evaluable participants on this protocol

• INCLUSION CRITERIA:
• Biopsy proven KSHV-associated MCD, confirmed in the Laboratory of Pathology (LP), CCR
• Age >=18 years.
• ECOG performance status <=4 (Karnofsky >=20%).
• Ability of subject to understand and the willingness to sign a written informed consent document.
• Participants may be co-enrolled in other protocols, including investigational studies to treat KSHV-associated malignancies.

Exclusion criteria

• Any condition or set of circumstances that in the opinion of the investigators would make participation in this study unsafe or otherwise inappropriate for a given individual.
• Pregnancy