Prognostic factors for Castleman disease include tumor diameter, lymphocyte count, estimated glomerular filtration rate and low-density lipoprotein cholesterol: a retrospective cohort study

 

Yumo Du^1,2, Shuangfeng Xie^2,3, Zhen Dai⁴, Wenjuan Li⁴, Long Zhang⁵, Haijiao Zhang⁶, Meiping Wu^2,3, Yiqing Li^2,3, Wenjuan Yang^2,3, Jie Xiao^2,3,Yongxun Zhuansun^1,2, Jianguo Li^1,2, Wenying Zhang⁷, Shanping Jiang^1,2, Danian Nie^2,3, Kezhi Huang^2,3,7,8

 

1Department of Respirology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.

2Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.

3Department of Hematology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.

4Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.

5Department of Pathology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.

6Department of Cell, Developmental & Cancer Biology, Knight Cancer Institute,

Oregon Health & Science University, Portland, OR, USA.

7Internal Medicine Ward Sixth, JieXi People’s Hospital (Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University-JieXi Medical Center), JieYang, China.

8Guangdong Provincial Key Laboratory of Cancer Pathogenesis and Precision Diagnosis and Treatment, Department of Hematology, Shenshan Medical Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Shanwei, Guangdong, China.

These authors are co-first authors: Yumo Du, Shuangfeng Xie.

These authors are co-corresponding authors: Danian Nie, Kezhi Huang.

e-mail: niedn@mail.sysu.edu.cn; huangkzh3@mail.sysu.edu.cn

 

 

Keywords: Castleman disease, Prognostic factors, Inflammation, Cholesterol

 

Background: Castleman disease (CD) is a rare and highly heterogeneous lymph-proliferative disorder. We aim to describe the clinical characteristics and identify prognostic factors from a large CD cohort over 11 years.

Methods: CD diagnosed at Sun Yat-sen Memorial Hospital, Sun Yat-sen University from 2012 to 2022 were enrolled. Approve from the Institutional Review Boards was available. General information, clinical manifestations, laboratory data, survival status of the patients were collected.  

Results: 77 CD patients [mean age 38.8 years, 60 unicentric CD (UCD), 17 multicentric CD (MCD)] were enrolled, with complicated disease manifestations, scattered departments of consultation. Compared to UCD, MCD exhibited more severe clinical manifestations, stronger inflammation, and multi-system involvement. However, some UCD could also present with MCD-like systemic inflammatory manifestations, highlighting the need for systemic treatment in addition to the resection. Univariate analysis revealed factors associated with adverse prognosis included older age (years, p=0.013), decreased lymphocyte count (×10⁹/L, p=0.011), B symptoms (p=0.037), tumor diameter > 6.3 cm (p=0.042), anemia (Hb < 100 g/L, p=0.008), albumin ≤ 33.5 g/L (p=0.033), C-reactive protein > 22.4 mg/L (p=0.002), decreased estimated glomerular filtration rate (eGFR) (< 60 ml/min•1.73 m², p=0.011), decreased total cholesterol (≤ 3.3 mmol/L, p=0.006), decreased high-density lipoprotein cholesterol (≤ 0.73 mmol/L, p=0.031), and decreased low-density lipoprotein cholesterol (≤ 2.11 mmol/L, p=0.013). Multivariate COX analysis indicated that the adverse prognostic factors for overall survival were comprised by large tumor diameter in centimeter (hazard ratio, HR 1.49, p=0.002), decreased lymphocyte count (×10⁹/L) (HR 0.12, p=0.027), eGFR < 60 ml/min•1.73m² (HR 7.16, p=0.017), and low-density lipoprotein cholesterol < 2.11 mmol/L (HR 4.85, p=0.032). To our knowledge, ours is the first study showing lower low-density lipoprotein cholesterol level is associated with poor prognosis of CD.

Conclusions: This study presents a large cohort depicting the varied clinical characteristics of CD, and the first report suggesting low-density lipoprotein cholesterol as a prognostic factor, providing novel insights for understanding CD. 

Acknowledgement

This work was supported by grants from Guangdong Science and Technology Department (#2024B1212030002), National Key Research and Development Program of China (2023YFC3404305, 2022YFF0710601), National Natural Science Foundation of China (32470891).