The clinical spectrum of Castleman's disease

Abstract

Castleman's disease (CD) is a rare, poorly understood lymphoproliferative disease. The spectrum of symptoms and course of disease are broad, but there is no large study describing the natural history of this disease. Basic clinic and laboratory data from the records of 113 patients with CD evaluated at the Mayo Clinic and University of Nebraska were abstracted. The impact of these variables on overall survival (OS) from time of diagnosis was evaluated. Sixty patients had multicentric disease. Of the patients with multicentric CD, 32% had criteria sufficient for a diagnosis of POEMS syndrome. For all patients, 2, 5, and 10-year OS was 92%, 76%, 59%, respectively. Most of the factors identified as risk factors for death on univariate analysis cosegregated with diagnostic criteria for POEMS syndrome, which supported the concept of four categories of CD, which are (along with their 5-year OS): (1) unicentric CD (91%); (2) multicentric CD associated with the osteosclerotic variant of POEMS syndrome (90%); (3); multicentric CD without POEMS syndrome (65%); and (4) multicentric CD with POEMS syndrome without osteosclerotic lesions (27%). We have demonstrated that CD represents a spectrum of disease that can be differentiated by simple prognostic factors that provide a framework for further study.

Figure 1. Interactions between histology, disease extent, and clinical features

A. Relationship of histology and disease extent. B. Relationship between disease extent, POEMS syndrome, osteosclerotic bone lesions, and peripheral neuropathy. All patients with osteosclerotic bone lesions had POEMS syndrome, and by definition all patients with POEMS had peripheral neuropathy, but one third of patients who had peripheral neuropathy did not have POEMS syndrome. MCD, multicentric Castelman's disease; UCD, unicentric Castleman's disease.

Figure 2. Kaplan meier estimates of overall survival

Differences between groups were calculated by log-rank A. By histology. 5 year OS for hyaline vascular, plasma cell variant, and mixed is 79%, 70%, and 100%. B. By extent of disease. 5 year overall survival for unicentric and multicentric is 91% and 65% respectively. C. By co-existing POEMS syndrome, osteosclerotic bone lesions, and peripheral neuropathy in patients with unicentric Castleman's disease. Limited follow-up for the 1 patient with POEMS syndrome associated with osteosclerotic bone lesions and the 2 patients without POEMS, but with peripheral neuropathy. D. By co-existing POEMS syndrome, osteosclerotic bone lesions, and peripheral neuropathy in patients with multicentric Castleman's disease. 5 year overall survival for 10 patients with osteosclerotic variant of POEMS syndrome was 90%, for 9 patients with POEMS syndrome without osteosclerotic lesions was 27%, and for 41 patients without POEMS who either had (n=8) or did not (n=33) have peripheral neuropathy was 51% and 65%, respectively. The combined 5-year OS blending the last two groups was 65%.

Figure 3. Treatment decisions and outcomes

A. Initial therapy based on unicentric or multicentric disease Due to missing data, total unicentric and multicentric cases are 46 (7 missing) and 57 (3 missing). B. Response to initial therapy based on extent of disease First line chemotherapy regimens used were cyclophosphamide/prednisone (n=4), chlorambucil/prednisone (n=2), cyclophosphamide/vincristine/mitroxantrone/prednisone (n=1), and interferon/prednisone (n=2; data not shown)