Abstract: Castleman disease (CD) presents a complex clinical scenario due to its rarity and heterogeneity. To deepen insights into this condition, we conducted a multicenter retrospective study across 40 Chinese institutions, encompassing 1634 CD patients diagnosed between 2000 and 2021. Following stringent diagnostic criteria established by the Castleman Disease Collaborative Network (CDCN), our study aimed to elucidate clinical features, treatment patterns, and prognostic factors associated with CD in China. Subtyping the CD cohort revealed distinct categories, with further subdivisions based on human herpesvirus-8 (HHV-8) association and clinical presentations. Notably, a significant proportion of patients exhibited an inflammatory state akin to multicentric CD, highlighting the importance of discerning between subtypes for tailored management strategies. Our findings revealed a notable shift in treatment paradigms, with a trend towards continuous therapeutic approaches. Survival analysis unveiled marked discrepancies among patient subtypes, emphasizing the dire prognosis associated with severe iMCD. This underscores the imperative for intensified therapeutic interventions in this subset. The study's robust methodology, encompassing a large patient cohort and adherence to stringent diagnostic criteria, provides a solid foundation for future research and guideline development.Introduction: Castleman disease (CD) is a rare lymphoproliferative disorder characterized by heterogeneous clinical manifestations and outcomes. Despite its rarity, CD poses significant diagnostic and therapeutic challenges due to its diverse presentations and limited understanding. Previous studies have highlighted the importance of subclassifying CD to tailor treatment strategies effectively. However, comprehensive data on CD, particularly in the Chinese population, are limited. To address this gap, we conducted a multicenter retrospective study aiming to characterize the clinical features, treatment patterns, and prognostic factors of CD in China, utilizing the diagnostic criteria established by the Castleman Disease Collaborative Network (CDCN). By elucidating the landscape of CD in China, our study aims to contribute to improved management strategies and outcomes for CD patients nationally and globally.
Study Design and Methods: The multicenter retrospective study aimed to elucidate the clinical features, treatment options, and prognostic factors of Castleman disease (CD) in China, following the diagnostic criteria set by the Castleman Disease Collaborative Network (CDCN). A total of 1634 patients diagnosed with CD from the years 2000 to 2021 at 40 Chinese institutions were included. The study subjects were divided into unicentric CD (UCD, n=903) and multicentric CD (MCD, n=731), with a further subclassification of MCD patients based on the presence of human herpesvirus-8 (HHV-8) and clinical symptoms into HHV8-MCD (n=12) and HHV-8-negative MCD, which included asymptomatic MCD (aMCD, n=139) and idiopathic MCD (iMCD, n=580). The iMCD patients were further categorized into iMCD meeting TAFRO criteria (n=41) and the remaining as iMCD-NOS. Data were collected and analyzed to portray clinical features, analyze treatment response, and conduct survival analysis.
Results: In the UCD cohort, 162 patients (17.9%) presented with an inflammatory state similar to MCD. Within the MCD group, the majority were HHV-8-negative (719 out of 731), with a small subset meeting the criteria for HHV8-MCD (12 patients). Among the iMCD patients, those fulfilling iMCD-TAFRO criteria made up 7.1%, while the rest were classified as iMCD-NOS, which included both iMCD with inflammatory plasma cell (iMCD-IPL) and without (iMCD-NOS). A shift in first-line treatment was observed, with a trend moving from pulse combination chemotherapy to continuous treatment options. Survival analysis revealed significant disparities between patient subtypes, indicating that severe iMCD patients had substantially worse outcomes (Hazard Ratio = 3.747; 95% Confidence Interval: 2.112–6.649, p<0.001). This suggests a need for more robust treatment strategies in this group.
Discussion: This retrospective study presents the largest dataset of CD in China to date, evaluated through the lens of stringent CDCN diagnostic criteria. The findings support the CDCN’s definition that severe iMCD is correlated with poorer patient outcomes and the necessity for intensive therapeutic approaches. The delineation among the subtypes of CD, particularly the differentiation between iMCD-TAFRO and iMCD-NOS, is crucial given the variations in treatment responses and prognoses. This study’s results validate the clinical relevance of the CDCN categories and provide a foundational dataset for further research and guideline development. One of the contributions of this study is demonstrating the trend toward continuous treatment strategies, reflecting an evolution in the management of CD that may align with international approaches for dealing with rare diseases requiring tailored care protocols. The study was funded by the Beijing Municipal Commission of Science and Technology, CAMS Innovation Fund, and National High-Level Hospital Clinical Research Funding, ensuring a robust backing for high-quality data collection and analysis. In complement, the open access nature of the data promotes transparency and supports global research collaboration on this rare but significant medical condition.
Conclusion: In conclusion, our multicenter retrospective study represents a significant advancement in understanding Castleman disease (CD) in China. Through the analysis of a large patient cohort spanning two decades and adherence to stringent diagnostic criteria set by the Castleman Disease Collaborative Network (CDCN), we have provided valuable insights into the clinical characteristics, treatment patterns, and prognostic factors associated with CD subtypes. Our findings reaffirm the clinical relevance of CDCN-defined subtypes, particularly in distinguishing between severe idiopathic multicentric CD (iMCD) subtypes such as iMCD-TAFRO and iMCD-NOS. Furthermore, the observed shift towards continuous treatment strategies underscores the evolving landscape of CD management, aligning with international approaches for rare diseases requiring tailored care protocols.
The study’s comprehensive analysis and findings were enriched by the collective effort of authors J.L., L.Z., and Dr. Dehui Zou, alongside numerous contributors from esteemed institutions across China. Their contributions, although not explicitly detailed in the provided excerpts, were instrumental in advancing the understanding of Castleman disease. Additionally, the publication of this research in The Lancet further underscores the significance of the study’s findings, providing a prestigious platform for disseminating impactful research in the medical community.
