Journal of Cancer Research and Clinical Oncology

, Volume 144, Issue 7, pp 1265–1277 | Cite as

Analysis of clinical characteristics and prognosis factors of 71 cases with HIV-negative Castleman’s disease: hypoproteinemia is an unfavorable prognostic factor which should be treated appropriately

  • Xuan Lan
  • Zhaoming Li
  • Mingzhi Zhang
Original Article – Cancer Research



HIV negative Castleman’s disease has been reported as a group of poorly understood lymphoproliferative disorder, and we want to explore the clinical feature and prognosis factors of CD.


We retrospectively collected the clinical information of 71 CD patients without HIV infection diagnosed in the first affiliated hospital of Zhengzhou university.


Different clinical classifications, including 35 patients (49.30%) with unicentric Castleman disease and 36 (50.7%) with multicentric Castleman disease, has their specific features compared with each other and unfavorable risk factors calculated by the univariate analysis. As for all of CD patients without HIV infection, there were 7 significant risk factors identified by the results of log-rank test, including clinical complaint, edema (hydrothorax, ascites, pelvic effusion), fatigue, anemia, hypoproteinemia and elevated serum β2-MG. Then, we created a Cox regression model of these clinical and statistic significant factors which indicated hypoproteinemia was an independent poor prognosis factors of CD in both univariate and multivariate analysis.


Our study emphasized the distinction of clinical characteristics between UCD and MCD and the importance of different poor risk factors of different clinical classifications which may directed more precise and appropriate treatment strategy.


Giant lymph node hyperplasia Castleman disease HIV Hypoproteinemia Prognostic factors 


Author contributions

X.L. and M.Z. designed the research; X.L. analyzed the data and wrote the paper; X.L. and Z.L. contribute to patient follow-up and data collection; Z.L. reviewed the pathological data.


This work was supported by a grant from the Natural Science Foundation, China (No. 81570203).

Compliance with ethical standards

Conflict of interest

The authors have no competing interests.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The ethical code is: science research-2015-LW-42. All patients in the study have consent for participation and provided follow-up record.


  1. Aoki Y, Tosato G, Fonville TW, Pittaluga S (2001) Serum viral interleukin-6 in AIDS-related multicentric Castleman disease. Blood 97:2526–2527CrossRefPubMedGoogle Scholar
  2. Casper C, Nichols WG, Huang ML, Corey L, Wald A (2004) Remission of HHV-8 and HIV-associated multicentric Castleman disease with ganciclovir treatment. Blood 103:1632–1634CrossRefPubMedGoogle Scholar
  3. Casper C, Teltsch DY, Robinson DJ, Desrosiers MP, Rotella P, Dispenzieri A, Qi M, Habermann T, Reynolds MW (2015a) Clinical characteristics and healthcare utilization of patients with multicentric Castleman disease. Br J Haematol 168:82–93CrossRefPubMedGoogle Scholar
  4. Casper C, Chaturvedi S, Munshi N, Wong R, Qi M, Schaffer M, Bandekar R, Hall B, Velde H, Vermeulen J, Reddy M, Rhee F (2015b) Analysis of inflammatory and anemia-related biomarkers in a randomized, double-blind, placebo-controlled study of siltuximab (anti-IL6 monoclonal antibody) in patients with multicentric Castleman disease. Clin Cancer Res 21:4294–4304CrossRefPubMedGoogle Scholar
  5. Castleman B, Iverson L, Menendez VP (1956) Localized mediastinal lymphnode hyperplasia resembling thymoma. Cancer 9:822CrossRefPubMedGoogle Scholar
  6. Chang KC, Wang YC, Hung LY, Huang WT, Tsou JH, Song HL, Yeh YM, Kao LY, Medeiros LJ (2014) Monoclonality and cytogenetic abnormalities in hyaline vascular Castleman disease. Mod Pathol 27:823CrossRefPubMedGoogle Scholar
  7. Chronowski GM, Ha CS, Wilder RB, Cabanillas F, Manning J, Cox JD (2015) Treatment of unicentric and multicentric Castleman disease and the role of radiotherapy. Cancer 92:670–676CrossRefGoogle Scholar
  8. Deisseroth A, Ko CW, Nie L, Zirkelbach JF, Zhao L, Bullock J, Mehrotra N, Del VP, Saber H, Sheth C (2015) FDA approval: siltuximab for the treatment of patients with multicentric Castleman disease. Clin Cancer Res 21(5):950CrossRefPubMedGoogle Scholar
  9. Dispenzieri A, Armitage JO, Loe MJ, Geyer SM, Allred J, Camoriano JK, Menke DM, Weisenburger DD, Ristow K, Dogan A (2012) The clinical spectrum of Castleman’s disease. Am J Hematol 87:997–1002CrossRefPubMedPubMedCentralGoogle Scholar
  10. Dong Y, Wang M, Nong L, Wang L, Cen X, Liu W, Zhu S, Sun Y, Liang Z, Li Y, Ou J, Qiu Z, Ren H (2015) Clinical and laboratory characterization of 114 cases of Castleman disease patients from a single centre: paraneoplastic pemphigus is an unfavourable prognostic factor. Br J Haematol 169:834–842CrossRefPubMedGoogle Scholar
  11. El-Osta H, Janku F, Kurzrock R (2010) Successful treatment of Castleman’s disease with interleukin-1 receptor antagonist (Anakinra). Mol Cancer Ther 9:1485CrossRefPubMedPubMedCentralGoogle Scholar
  12. Fajgenbaum DC, Rhee FV, Nabel CS (2014) HHV-8-negative, idiopathic multicentric Castleman disease: novel insights into biology, pathogenesis, and therapy. Blood 123:2924CrossRefPubMedGoogle Scholar
  13. Galeotti C, Tran TA, Franchi-Abella S, Fabre M, Pariente D, Kone-Paut I (2008) IL-1RA agonist (anakinra) in the treatment of multifocal Castleman disease: case report. J Pediatr Hematol Oncol 30:920–924CrossRefPubMedGoogle Scholar
  14. Gérard L, Berezne A, Galicier L, Meignin V, Obadia M, De Castro N, Jacomet C, Verdon R, Madelaine-Chambrin I, Boulanger E, Chevret S, Agbalika F, Oksenhendler E (2007) Prospective study of rituximab in chemotherapy-dependent human immunodeficiency virus associated multicentric Castleman’s disease: ANRS 117 CastlemaB Trial. J Clin Oncol 25:3350–3356CrossRefPubMedGoogle Scholar
  15. Gérard L, Michot JM, Burcheri S, Fieschi C, Longuet P, Delcey V, Meignin V, Agbalika F, Chevret S, Oksenhendler E (2012) Rituximab decreases the risk of lymphoma in patients with HIV-associated multicentric Castleman disease. Blood 119:2228CrossRefPubMedGoogle Scholar
  16. Herrada J, Cabanillas F, Rice L, Manning J, Pugh W (1998) The clinical behavior of localized and multicentric Castleman disease. Ann Intern Med 128:657–662CrossRefPubMedGoogle Scholar
  17. Hess G, Wagner V, Kreft A, Heussel CP, Huber C (2006) Effects of bortezomib on pro-inflammatory cytokine levels and transfusion dependency in a patient with multicentric Castleman disease. Br J Haematol 134:544–545CrossRefPubMedGoogle Scholar
  18. Hoffmann C, Schmid H, Muller M, Teutsch C, van Lunzen J, Esser S, Wolf T, Wyen C, Sabranski M, Horst HA, Reuter S, Vogel M, Jager H, Bogner J, Arasteh K (2011) Improved outcome with rituximab in patients with HIV-associated multicentric Castleman disease. Blood 118:3499–3503CrossRefPubMedGoogle Scholar
  19. Ibrahim HA, Balachandran K, Bower M, Naresh KN (2016) Bone marrow manifestations in multicentric Castleman disease. Br J Haematol 172:923–929CrossRefPubMedGoogle Scholar
  20. Keller AR, Hochholzer L, Castleman B (1972) Hyaline-vascular and plasma-cell types of giant lymph node hyperplasia of the mediastinum and other locations. Cancer 29:670CrossRefPubMedGoogle Scholar
  21. Liu AY, Nabel CS, Finkelman BS, Ruth JR, Kurzrock R, Van RF, Krymskaya VP, Kelleher D, Rubenstein AH, Fajgenbaum DC (2016) Idiopathic multicentric Castleman’s disease: a systematic literature review. Lancet Haematol 3:163–175CrossRefGoogle Scholar
  22. Nishimoto N, Terao K, Mima T, Nakahara H, Takagi N, Kakehi T (2008) Mechanisms and pathologic significances in increase in serum interleukin-6 (IL-6) and soluble IL-6 receptor after administration of an anti-IL-6 receptor antibody, tocilizumab, in patients with rheumatoid arthritis and Castleman disease. Blood 112: 3959–3964CrossRefPubMedGoogle Scholar
  23. Ohsugi Y, Tsuchimoto N (2005) Pharmacological and clinical profile of anti-human IL-6 receptor antibody (tocilizumab, ACTEMRA), a novel therapeutic drug for Castleman’s disease. Nihon Yakurigaku Zasshi 126:419–425CrossRefPubMedGoogle Scholar
  24. Oksenhendler E, Carcelain G, Aoki Y, Boulanger E, Maillard A, Clauvel JP, Agbalika F (2000) High levels of human herpesvirus 8 viral load, human interleukin-6, interleukin-10, and C reactive protein correlate with exacerbation of multicentric Castleman disease in HIV-infected patients. Blood 96:2069–2073PubMedGoogle Scholar
  25. Ramasamy K, Gandhi S, Tenant-Flowers M, Ceesay M, Corderoy S, Marcus R, Schey S (2012) Rituximab and thalidomide combination therapy for Castleman disease. Br J Haematol 158:421–423CrossRefPubMedGoogle Scholar
  26. Seo HY, Kim EB, Kim JW, Shin BK, Kim SJ, Kim BS (2009) Complete remission in a patient with human herpes virus-8 negative multicentric Castleman disease using CHOP chemotherapy. Cancer Res Treat 41:104–107CrossRefPubMedPubMedCentralGoogle Scholar
  27. Seo S, Yoo C, Yoon DH, Kim S, Park JS, Park CS, Huh J, Suh C (2014) Clinical features and outcomes in patients with human immunodeficiency virus-negative, multicentric Castleman’s disease: a single medical center experience. Blood Res 49:253CrossRefPubMedPubMedCentralGoogle Scholar
  28. Soulier J, Grollet L, Oksenhendler E, Miclea JM, Cacoub P, Baruchel A, Brice P, Clauvel JP, D’Agay MF, Raphael M (1995) Molecular analysis of clonality in Castleman’s disease. Blood 86:1131PubMedGoogle Scholar
  29. Suda T, Katano H, Delsol G, Kakiuchi C, Nakamura T, Shiota M, Sata T, Higashihara M, Mori S (2001) HHV-8 infection status of AIDS-unrelated and AIDS-associated multicentric Castleman’s disease. Pathol Int 51:671–679CrossRefPubMedGoogle Scholar
  30. Szturz P, Adam Z, Moulis M, Smardova L, Klincova M, Slaisova R, Koukalova R, Rehak Z, Volfova P, Chovancova J, Stehlikova O, Mayer J (2012) [Our experience in treatment of multicentric plasma-cell Castleman disease associated with vasculitis manifestations—case report and literature review]. Vnitr Lek 58:679–690PubMedGoogle Scholar
  31. Talat N, Schulte KM (2011) Castleman’s disease: systematic analysis of 416 patients from the literature. Oncologist 16:1316CrossRefPubMedPubMedCentralGoogle Scholar
  32. Talat N, Belgaumkar AP, Schulte KM (2012) Surgery in Castleman’s disease: a systematic review of 404 published cases. Ann Surg 255:677CrossRefPubMedGoogle Scholar
  33. Uldrick TS, Polizzotto MN, Aleman K, Wyvill KM, Marshall V, Whitby D, Wang V, Pittaluga S, O’Mahony D, Steinberg SM (2014) Rituximab plus liposomal doxorubicin in HIV-infected patients with KSHV-associated multicentric Castleman disease. Blood 124:3544CrossRefPubMedPubMedCentralGoogle Scholar
  34. Van Rhee F, Wong RS, Munshi N, Rossi JF, Ke XY, Fosså A, Simpson D, Capra M, Liu T, Hsieh RK, Goh YT, Zhu J, Cho SG, Ren H, Cavet J, Bandekar R, Rothman M, Puchalski TA, Reddy M, van de Velde H, Vermeulen J, Casper C (2014a) Siltuximab for multicentric Castleman’s disease: a randomised, double-blind, placebo-controlled trial. The Lancet Oncology 15:966–974CrossRefPubMedGoogle Scholar
  35. van Rhee F, Wong RS, Munshi N, Rossi JF, Ke XY, Fossa A, Simpson D, Capra M, Liu T, Hsieh RK, Goh YT, Zhu J, Cho SG, Ren H, Cavet J, Bandekar R, Rothman M, Puchalski TA, Reddy M, van de Velde H, Vermeulen J, Casper C (2014b) Siltuximab for multicentric Castleman’s disease: a randomised, double-blind, placebo-controlled trial. Lancet Oncol 15:966–974CrossRefPubMedGoogle Scholar
  36. Yoshizaki K, Matsuda T, Nishimoto N, Kuritani T, Taeho L, Aozasa K, Nakahata T, Kawai H, Tagoh H, Komori T (1989) Pathogenic significance of interleukin-6 (IL-6/BSF-2) in Castleman’s disease. Blood 74:1360PubMedGoogle Scholar
  37. 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 129:1658–1668CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of OncologyThe First Affiliated Hospital of Zhengzhou UniversityZhengzhouChina

Personalised recommendations