By Clinical Research News Staff 

June 10, 2025 | Researchers have made a landmark discovery in rare disease clinical research by identifying a new subtype of Castleman disease, marking the first major advancement in disease classification since the 1970s. The breakthrough demonstrates how patient-driven research registries can overcome traditional barriers in rare disease studies to generate clinically meaningful insights. 

Registry-Enabled Discovery 

The discovery of oligocentric Castleman disease (OligoCD) emerged from the ACCELERATE natural history registry, a patient-centered research platform that has revolutionized how clinical data is collected for this rare lymph node disorder. Unlike traditional clinical studies that require patients to travel to specific research centers, ACCELERATE allows patients worldwide to self-enroll and contribute their medical records remotely.  

Sheila Pierson, senior research advisor for the Castleman Disease Collaborative Network (CDCN), previously served as director of clinical research for the Center for Cytokine Storm Treatment & Laboratory (CSTL) at the University of Pennsylvania that has been building ACCELERATE since 2016.  

The ACCELERATE approach addresses a fundamental challenge in rare disease research: the geographic dispersion of small patient populations. With fewer than 2,000 cases diagnosed annually in the United States, assembling sufficient patient cohorts for meaningful analysis has historically proven nearly impossible through conventional clinical research methods. 

The research team at the University of Pennsylvania analyzed 343 enrolled cases, implementing a comprehensive validation process that included expert panel reviews and diagnostic confirmation procedures. After excluding cases lacking sufficient radiologic documentation or expert confirmation, 179 cases remained for analysis, leading to the identification of the oligocentric subtype that characterizes approximately 15% of all Castleman disease cases. 

The newly identified subtype presents with fewer and less severe symptoms compared to the established unicentric and multicentric classifications, suggesting distinct treatment approaches may be warranted. Clinical evidence indicates oligocentric patients demonstrate reduced inflammatory markers compared to multicentric cases, potentially requiring less aggressive therapeutic interventions while still needing enhanced monitoring protocols. 

Clinical Implications and Treatment Considerations 

The discovery has immediate implications for clinical practice and treatment decision-making. Current evidence suggests oligocentric patients may benefit from treatment approaches more similar to those used for unicentric cases rather than the intensive therapies typically required for multicentric disease. However, the research indicates these patients require additional monitoring due to the potential for subsequent disease involvement. 

This finding underscores the importance of personalized medicine approaches in rare disease management, where subtle differences in disease presentation can significantly impact optimal treatment strategies. 

Patient-Driven Research Model 

The success of this discovery highlights the effectiveness of patient-driven research initiatives in advancing rare disease understanding. The ACCELERATE registry, now supporting over 800 enrolled patients, is supported through a grant from the FDA Office of Orphan Products Development.  

The registry's patient-centric approach includes regular community meetings and surveys addressing research questions important to patients themselves. This collaborative model ensures research priorities align with patient needs while maintaining scientific rigor through expert adjudication processes for diagnostic validation. 

Ongoing Clinical Research Directions 

With only 14 oligocentric patients identified in the initial study cohort, researchers continue collecting data to better understand optimal treatment approaches for this newly recognized subtype. The research team plans to evaluate emerging treatment patterns and identify potentially beneficial therapeutic interventions as the patient population grows. 

If clear treatment signals emerge from continued data collection, clinical trials specifically targeting oligocentric Castleman disease may be developed, potentially providing evidence-based treatment guidelines for this newly characterized patient population. 

For the full story by Deborah Borfitz, see Diagnostics World News.