A Novel Predictive Model for Idiopathic Multicentric Castleman Disease: The International Castleman Disease Consortium Study.
BACKGROUND
Patients with multicentric Castleman disease (MCD) who are negative for human immunodeficiency virus and human herpesvirus 8 are considered to have idiopathic MCD (iMCD). The clinical presentation of iMCD varies from mild constitutional symptoms to life-threatening symptoms or death. The treatment strategy varies from "watchful waiting" to high-dose chemotherapy. This diverse clinical presentation calls for a classification stratification system that takes into account the severity of the disease.


SUBJECTS, MATERIALS, AND METHODS
We analyzed the clinical, laboratory, and pathologic abnormalities and treatment outcomes of 176 patients with iMCD (median follow-up duration 12 years) from the U.S. and China to better understand the characteristics and prognostic factors of this disease. This discovery set of iMCD results was confirmed from the validation set composed of an additional 197 patients with iMCD organized from The International Castleman Disease Consortium.


RESULTS
Using these data, we proposed and validated the iMCD international prognostic index (iMCD-IPI), which includes parameters related to patient characteristics (age > 40 years), histopathologic features (plasmacytic variant subtype), and inflammatory consequences of iMCD (hepatomegaly and/or splenomegaly, hemoglobin <80 g/L, and pleural effusion). These five factors stratify patients according to their performance status and extent of organ dysfunction into three broad categories: low risk, intermediate risk, and high risk. The iMCD-IPI score accurately predicted outcomes in the discovery study cohort, and the results were confirmed on the validation study cohort.


CONCLUSION
This study represents the largest series of studies on patients with iMCD in the field and proposed a novel risk-stratification model for iMCD-IPI that could be used to guide risk-stratified treatment strategies in patients with iMCD.


IMPLICATIONS FOR PRACTICE
Although patients with human herpesvirus 8-negative/human immunodeficiency virus-negative multicentric Castleman disease (iMCD) are heterogeneous in clinical, histologic, and subtyping features, they benefit from empirical treatment with decision largely based on clinical evaluation from clinical symptom and disease severity. This prospective study initiated from 176 patients with iMCD interestingly showed that five clinical factors, including age > 40 years, plasmacytic variant subtype, hepatomegaly and/or splenomegaly, hemoglobin <80 g/L, and pleural effusion, could stratify patients into three risk categories: low risk, intermediate risk, and high risk. Such stratification significantly correlates with the clinical performance status and extent of organ dysfunction in these patients enrolled in the study. The validation set of an additional 197 patients with iMCD organized from The International Castleman Disease Consortium was established to confirm and further refine the results from the initial discovery data set. The proposed novel model fully uses relevant clinical parameters and is able to achieve valuable predictive outcomes and support for optimal therapy selection.