Castleman disease spectrum.

Abstract

8548 Background: Castleman disease (CD) describes a group of lymphoproliferative disorders that share characteristic histopathology. Unicentric CD (UCD) and idiopathic multicentric CD (iMCD) are differentiated by the number of enlarged lymph node (LN) regions: UCD involves 1 region and iMCD involves > 1 region. UCD typically has mild or no symptoms whereas iMCD requires abnormal labs and symptoms for diagnosis and can progress to life-threatening multi-organ failure. Review of an international natural history registry of CD revealed patients across a broad spectrum with regards to number of enlarged LN regions and disease severity. We hypothesize that there is a positive correlation between disease activity and the number of enlarged LNs and that the spectrum of CD is more complex than a binary UCD-iMCD dichotomy. Methods: Herein, enrolled UCD and iMCD patients whose diagnosis was confirmed by an expert-panel were selected for analysis (N = 81). A standardized disease activity score (scale 0-1) was computed for each patient using available diagnostic values of C-reactive protein, hemoglobin, and albumin (CHA score). Results: We looked at the association between number of enlarged LNs and CHA and found a significant positive correlation (R = 0.65, p < 0.0001). Given this, we divided the cohort into groups of mild, moderate, and extensive lymphadenopathy according to the number of regions of enlarged LNs at the time of diagnosis: group 1 (1 enlarged LN region); group 2 (2-4 enlarged LN regions); and group 3 (≥5 enlarged LN regions). We identified 20 patients in group 1, 19 in group 2, and 42 in group 3 with no statistical differences in sex, race, or age at diagnosis. Histopathological subtype differed significantly among groups. Group 1 was 89% hyaline vascular (HV)/ hypervascular (HpV) and 11% mixed (Mx); group 2 was 74% HV/HpV, 21% Mx, and 5% plasmacytic (Pl); and group 3 was 64% HV/HpV, 32% Mx, and 5% Pl. We then looked at CHA score in these groups and found that group 3 patients have a significantly greater CHA score (median [IQR]: 0.46 [0.49]) than both group 2 (0.08 [0.14]) and group 1 (0.0 [0.10]) (adjusted p < 0.001 for both) while there was no difference between groups 1 and 2. Conclusions: These results suggest that disease severity is positively associated with the number of enlarged LNs. The different proportions of histopathological subtypes between the three groups could indicate different pathologic mechanisms are involved. Further work is needed to determine if patients with a few enlarged LNs exhibit disease more closely to UCD or iMCD and to understand long-term outcomes for these patients.

ACCELERATE: A Patient-Powered Natural History Study Design Enabling Clinical and Therapeutic Discoveries in a Rare Disorder

“…To identify patient subgroups, a study is under way to characterize the full spectrum of CD, specifically evaluating patients who do not clearly fall into the UCD or iMCD subgroups and do not carry an alternative or exclusionary diagnosis. 13 Clinical data recorded in ACCELERATE are being Article ll OPEN ACCESS analyzed along with corresponding CT and PET/CT images that were obtained through the ACCELERATE data collection process. To assess real-world response and safety profiles, an indepth examination of treatments is also under way.…”