Page 182 - Haematologica Vol. 109 - July 2024

ARTICLE - Non-Hodgkin Lymphoma
Longitudinal, natural history study reveals the disease
burden of idiopathic multicentric Castleman disease
Mateo Sarmiento Bustamante,1* Sheila K. Pierson,1* Yue Ren,2 Adam Bagg,3 Joshua D. Brandstadter,4 Gordan Srkalovic,5 Natalie Mango,1 Daisy Alapat,6 Mary Jo Lechowicz,7 Hongzhe Li,2 Frits van Rhee,8 Megan S. Lim9 and David C. Fajgenbaum1
1Center for Cytokine Storm Treatment & Laboratory, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; 2Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; 3Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA; 4Division of Hematology/Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; 5Sparrow Herbert-Herman Cancer Center, Michigan State University College of Human Medicine, Lansing, MI; 6Department of Pathology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR; 7Department of Hematology and Medical Oncology, Emory University School of Medicine and Winship Cancer Institute, Atlanta, GA; 8Myeloma Center, Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, AR and 9Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York City, NY, USA.
*MSB and SKP contributed equally as first authors.
Abstract
Idiopathic multicentric Castleman disease (iMCD) is a rare hematologic disorder with heterogeneous presentations ranging from moderate constitutional symptoms to life-threatening multiorgan system involvement. There are vastly different clin- ical subtypes, with some patients demonstrating thrombocytopenia, anasarca, fever/elevated C-reactive protein, reticulin fibrosis/renal failure, and organomegaly (TAFRO) and others having milder/more moderate symptoms with potential for severe disease (not otherwise specified, NOS). Due to its rarity and heterogeneity, the natural history and long-term burden of iMCD are poorly understood. We investigated real-world medical data from ACCELERATE, a large natural history registry of patients with Castleman disease, to better characterize the long-term disease burden experienced by these patients. We found that iMCD-TAFRO patients face a significant hospitalization burden, requiring more time in the hospital than iMCD- NOS patients during the year surrounding diagnosis (median [interquartile range]: 36 [18-61] days vs. 0 [0-4] days; P<0.001). In addition, we found life-sustaining interventions, such as mechanical ventilation (17%) and dialysis (27%), were required among iMCD patients, predominantly those with iMCD-TAFRO. iMCD-NOS patients, however, spent a significantly greater proportion of time following disease onset in a state of disease flare (median 52.3% vs. 18.9%; P=0.004). Lastly, we observed severe iMCD-related morbidities, such as acute renal failure, sepsis and pneumonia, among others, arising after iMCD di- agnosis, impairing the patients’ quality of life. These data demonstrate a substantial disease burden experienced by iMCD patients and emphasize the importance of ongoing research into iMCD to aid disease control.
Introduction
Idiopathic multicentric Castleman disease (iMCD) is a rare lymphoproliferative disorder characterized by widespread lymphadenopathy and a systemic inflammatory syndrome. While the pathophysiology of the disease remains poorly understood, existing data have implicated interleukin 6 and the mTOR and JAK-STAT pathways.1-5 As with other inflammatory disorders, iMCD is characterized by constitu-
tional symptoms and systemic inflammation that can lead to multiorgan failure or death.6 Several different clinical subtypes of iMCD have been identified. Patients with the most severe subtype who demonstrate thrombocytope- nia, anasarca, fever/elevated C-reactive protein, reticulin fibrosis/renal failure, and organomegaly are classified as having the TAFRO subtype.7 Other patients who do not meet TAFRO criteria are said to have iMCD not otherwise specified (NOS) and typically present with a milder clinical
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Correspondence: D.C. Fajgenbaum davidfa@pennmedicine.upenn.edu
Received: Accepted: Early view:
June 13, 2023. December 29, 2023. January 11, 2024.
https://doi.org/10.3324/haematol.2023.283603
©2024 Ferrata Storti Foundation Published under a CC BY-NC license