Clinical and pathological characteristics of HIV-and HHV-8-negative Castleman disease

Li Yu, Meifeng Tu, Jorge Cortes, Zijun Y. Xu-Monette, Roberto N. Miranda, Jun Zhang, Robert Z. Orlowski, Sattva Neelapu, Prajwal C. Boddu, Mary A. Akosile, Thomas S. Uldrick, Robert Yarchoan, L. Jeffrey Medeiros, Yong Li, David C. Fajgenbaum, Ken H. Young

Research output: Contribution to journalArticle

Abstract

Castleman disease (CD) comprises 3 poorly understood lymphoproliferative variants sharing several common histopathological features. Unicentric CD (UCD) is localized to a single region of lymph nodes. Multicentric CD (MCD) manifests with systemic inflammatory symptoms and organ dysfunction due to cytokine dysregulation and involves multiple lymph node regions. Human herpesvirus 8 (HHV-8) causes MCD (HHV- 8-associated MCD) in immunocompromised individuals, such as HIV-infected patients. However, >50% of MCD cases are HIV and HHV-8 negative (defined as idiopathic [iMCD]). The clinical and biological behavior of CD remains poorly elucidated. Here, we analyzed the clinicopathologic features of 74 patients (43 with UCD and 31 with iMCD) and therapeutic responseof 96patients (43 withUCDand53 with iMCD)with HIV-/HHV-8-negative CD compared with 51 HIV-/HHV-8-positive patients. Systemic inflammatory symptoms and elevated inflammatory factors were more common in iMCD patients than UCD patients. Abnormal bone marrow features were more frequent in iMCD (77.0%) than UCD (45%); the most frequent was plasmacytosis, which was seen in 3% to 30.4% of marrow cells. In the lymph nodes, higher numbers of CD31 lymphocytes (median, 58.88620.57) and lower frequency of CD191/CD51 (median, 5.8866.52) were observed in iMCD patients compared with UCD patients (median CD31 cells, 43.19 6 17.37; median CD191/CD51 cells, 17.37 6 15.80). Complete surgical resection is a better option for patients with UCD. Siltuximab had a greater proportion of complete responses and longer progressionfree survival (PFS) for iMCD than rituximab. Centricity, histopathological type, and anemia significantly impacted PFS. This study reveals that CD represents a heterogeneous group of diseases with differential immunophenotypic profiling and treatment response.

Original languageEnglish (US)
Pages (from-to)1658-1668
Number of pages11
JournalBlood
Volume129
Issue number12
DOIs
StatePublished - Mar 23 2017

Fingerprint

Giant Lymph Node Hyperplasia
Human Herpesvirus 8
HIV
Lymph Nodes
Bone Marrow
Lymphocytes
Survival
Lymphocyte Count
Bone
Anemia
Cells
Cytokines

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Yu, L., Tu, M., Cortes, J., Xu-Monette, Z. Y., Miranda, R. N., Zhang, J., ... Young, K. H. (2017). Clinical and pathological characteristics of HIV-and HHV-8-negative Castleman disease. Blood, 129(12), 1658-1668. https://doi.org/10.1182/blood-2016-11-748855

Clinical and pathological characteristics of HIV-and HHV-8-negative Castleman disease. / Yu, Li; Tu, Meifeng; Cortes, Jorge; Xu-Monette, Zijun Y.; Miranda, Roberto N.; Zhang, Jun; Orlowski, Robert Z.; Neelapu, Sattva; Boddu, Prajwal C.; Akosile, Mary A.; Uldrick, Thomas S.; Yarchoan, Robert; Medeiros, L. Jeffrey; Li, Yong; Fajgenbaum, David C.; Young, Ken H.

In: Blood, Vol. 129, No. 12, 23.03.2017, p. 1658-1668.

Research output: Contribution to journalArticle

Yu, L, Tu, M, Cortes, J, Xu-Monette, ZY, Miranda, RN, Zhang, J, Orlowski, RZ, Neelapu, S, Boddu, PC, Akosile, MA, Uldrick, TS, Yarchoan, R, Medeiros, LJ, Li, Y, Fajgenbaum, DC & Young, KH 2017, 'Clinical and pathological characteristics of HIV-and HHV-8-negative Castleman disease', Blood, vol. 129, no. 12, pp. 1658-1668. https://doi.org/10.1182/blood-2016-11-748855
Yu, Li ; Tu, Meifeng ; Cortes, Jorge ; Xu-Monette, Zijun Y. ; Miranda, Roberto N. ; Zhang, Jun ; Orlowski, Robert Z. ; Neelapu, Sattva ; Boddu, Prajwal C. ; Akosile, Mary A. ; Uldrick, Thomas S. ; Yarchoan, Robert ; Medeiros, L. Jeffrey ; Li, Yong ; Fajgenbaum, David C. ; Young, Ken H. / Clinical and pathological characteristics of HIV-and HHV-8-negative Castleman disease. In: Blood. 2017 ; Vol. 129, No. 12. pp. 1658-1668.
@article{f538cadb85304ce28a9a3b2d5e1cd0fc,
title = "Clinical and pathological characteristics of HIV-and HHV-8-negative Castleman disease",
abstract = "Castleman disease (CD) comprises 3 poorly understood lymphoproliferative variants sharing several common histopathological features. Unicentric CD (UCD) is localized to a single region of lymph nodes. Multicentric CD (MCD) manifests with systemic inflammatory symptoms and organ dysfunction due to cytokine dysregulation and involves multiple lymph node regions. Human herpesvirus 8 (HHV-8) causes MCD (HHV- 8-associated MCD) in immunocompromised individuals, such as HIV-infected patients. However, >50{\%} of MCD cases are HIV and HHV-8 negative (defined as idiopathic [iMCD]). The clinical and biological behavior of CD remains poorly elucidated. Here, we analyzed the clinicopathologic features of 74 patients (43 with UCD and 31 with iMCD) and therapeutic responseof 96patients (43 withUCDand53 with iMCD)with HIV-/HHV-8-negative CD compared with 51 HIV-/HHV-8-positive patients. Systemic inflammatory symptoms and elevated inflammatory factors were more common in iMCD patients than UCD patients. Abnormal bone marrow features were more frequent in iMCD (77.0{\%}) than UCD (45{\%}); the most frequent was plasmacytosis, which was seen in 3{\%} to 30.4{\%} of marrow cells. In the lymph nodes, higher numbers of CD31 lymphocytes (median, 58.88620.57) and lower frequency of CD191/CD51 (median, 5.8866.52) were observed in iMCD patients compared with UCD patients (median CD31 cells, 43.19 6 17.37; median CD191/CD51 cells, 17.37 6 15.80). Complete surgical resection is a better option for patients with UCD. Siltuximab had a greater proportion of complete responses and longer progressionfree survival (PFS) for iMCD than rituximab. Centricity, histopathological type, and anemia significantly impacted PFS. This study reveals that CD represents a heterogeneous group of diseases with differential immunophenotypic profiling and treatment response.",
author = "Li Yu and Meifeng Tu and Jorge Cortes and Xu-Monette, {Zijun Y.} and Miranda, {Roberto N.} and Jun Zhang and Orlowski, {Robert Z.} and Sattva Neelapu and Boddu, {Prajwal C.} and Akosile, {Mary A.} and Uldrick, {Thomas S.} and Robert Yarchoan and Medeiros, {L. Jeffrey} and Yong Li and Fajgenbaum, {David C.} and Young, {Ken H.}",
year = "2017",
month = "3",
day = "23",
doi = "10.1182/blood-2016-11-748855",
language = "English (US)",
volume = "129",
pages = "1658--1668",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "12",

}

TY - JOUR

T1 - Clinical and pathological characteristics of HIV-and HHV-8-negative Castleman disease

AU - Yu, Li

AU - Tu, Meifeng

AU - Cortes, Jorge

AU - Xu-Monette, Zijun Y.

AU - Miranda, Roberto N.

AU - Zhang, Jun

AU - Orlowski, Robert Z.

AU - Neelapu, Sattva

AU - Boddu, Prajwal C.

AU - Akosile, Mary A.

AU - Uldrick, Thomas S.

AU - Yarchoan, Robert

AU - Medeiros, L. Jeffrey

AU - Li, Yong

AU - Fajgenbaum, David C.

AU - Young, Ken H.

PY - 2017/3/23

Y1 - 2017/3/23

N2 - Castleman disease (CD) comprises 3 poorly understood lymphoproliferative variants sharing several common histopathological features. Unicentric CD (UCD) is localized to a single region of lymph nodes. Multicentric CD (MCD) manifests with systemic inflammatory symptoms and organ dysfunction due to cytokine dysregulation and involves multiple lymph node regions. Human herpesvirus 8 (HHV-8) causes MCD (HHV- 8-associated MCD) in immunocompromised individuals, such as HIV-infected patients. However, >50% of MCD cases are HIV and HHV-8 negative (defined as idiopathic [iMCD]). The clinical and biological behavior of CD remains poorly elucidated. Here, we analyzed the clinicopathologic features of 74 patients (43 with UCD and 31 with iMCD) and therapeutic responseof 96patients (43 withUCDand53 with iMCD)with HIV-/HHV-8-negative CD compared with 51 HIV-/HHV-8-positive patients. Systemic inflammatory symptoms and elevated inflammatory factors were more common in iMCD patients than UCD patients. Abnormal bone marrow features were more frequent in iMCD (77.0%) than UCD (45%); the most frequent was plasmacytosis, which was seen in 3% to 30.4% of marrow cells. In the lymph nodes, higher numbers of CD31 lymphocytes (median, 58.88620.57) and lower frequency of CD191/CD51 (median, 5.8866.52) were observed in iMCD patients compared with UCD patients (median CD31 cells, 43.19 6 17.37; median CD191/CD51 cells, 17.37 6 15.80). Complete surgical resection is a better option for patients with UCD. Siltuximab had a greater proportion of complete responses and longer progressionfree survival (PFS) for iMCD than rituximab. Centricity, histopathological type, and anemia significantly impacted PFS. This study reveals that CD represents a heterogeneous group of diseases with differential immunophenotypic profiling and treatment response.

AB - Castleman disease (CD) comprises 3 poorly understood lymphoproliferative variants sharing several common histopathological features. Unicentric CD (UCD) is localized to a single region of lymph nodes. Multicentric CD (MCD) manifests with systemic inflammatory symptoms and organ dysfunction due to cytokine dysregulation and involves multiple lymph node regions. Human herpesvirus 8 (HHV-8) causes MCD (HHV- 8-associated MCD) in immunocompromised individuals, such as HIV-infected patients. However, >50% of MCD cases are HIV and HHV-8 negative (defined as idiopathic [iMCD]). The clinical and biological behavior of CD remains poorly elucidated. Here, we analyzed the clinicopathologic features of 74 patients (43 with UCD and 31 with iMCD) and therapeutic responseof 96patients (43 withUCDand53 with iMCD)with HIV-/HHV-8-negative CD compared with 51 HIV-/HHV-8-positive patients. Systemic inflammatory symptoms and elevated inflammatory factors were more common in iMCD patients than UCD patients. Abnormal bone marrow features were more frequent in iMCD (77.0%) than UCD (45%); the most frequent was plasmacytosis, which was seen in 3% to 30.4% of marrow cells. In the lymph nodes, higher numbers of CD31 lymphocytes (median, 58.88620.57) and lower frequency of CD191/CD51 (median, 5.8866.52) were observed in iMCD patients compared with UCD patients (median CD31 cells, 43.19 6 17.37; median CD191/CD51 cells, 17.37 6 15.80). Complete surgical resection is a better option for patients with UCD. Siltuximab had a greater proportion of complete responses and longer progressionfree survival (PFS) for iMCD than rituximab. Centricity, histopathological type, and anemia significantly impacted PFS. This study reveals that CD represents a heterogeneous group of diseases with differential immunophenotypic profiling and treatment response.

UR - http://www.scopus.com/inward/record.url?scp=85016251572&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85016251572&partnerID=8YFLogxK

U2 - 10.1182/blood-2016-11-748855

DO - 10.1182/blood-2016-11-748855

M3 - Article

C2 - 28100459

AN - SCOPUS:85016251572

VL - 129

SP - 1658

EP - 1668

JO - Blood

JF - Blood

SN - 0006-4971

IS - 12

ER -