Full Text Article

Multicentric Castleman’s Disease Experience in an HIV Treatment Network

Received Date: November 27, 2020 Accepted Date: December 28, 2020 Published Date: December 30, 2020

doi: 10.17303/jaid.2020.7.202

Citation: Jose A Giron, Joseph Knipe, Khalil Nasser, Moti Ramgopal, Cynthia Rivera, et al. (2020) Multicentric Castleman’s Disease Experience in an HIV Treatment Network. J HIV AIDS Infect Dis 8: 1-4.

We present the experience with treatment of multicentric Castleman’s disease in a network of 12 practices dedicated to the treatment of HIV disease and other infectious diseases. A total of 4 cases were found. Three out of 4 patients received chemotherapy treatment, which included rituximab. All treated patients responded and have experienced a remission lasting from 5 to 89 months.

Keywords: SARS-COV-2; COVID-19; Multi-drug resistant HIV; Micro-embolic disease; Ischemia

Dr. Benjamin Castleman first described a unicentric lymphoproliferative disease in 1954, later referred to as Castleman’s disease [1,2]. Several authors later noted multicentric lymphadenopathies with similar histological features [3-6]. The unicentric form of Castleman’s disease presents as a solitary adenopathy, typically affecting a thoracic lymph node [7]. The multicentric form causes a syndrome of diffuse adenopathy, thrombocytopenia, hemolytic anemia, and fever often resulting in death with a 3-year disease-free survival rate of 40% [7,8]. Since these descriptions, a subset of multicentric Castleman’s disease (MCD) has been shown to be a result of Human Herpes-8 (HHV-8) infection [9]. HHV-8 can be found in variable prevalence in different geographic locales and different risk groups [10]. Infection rates of HHV-8 are highly associated with both homosexual activity among men and HIV positive status [11]. The HHV-8 negative cases of MCD remain idiopathic (iMCD) [12].

Another variant of HHV-8 related disease is primary effusion lymphoma [13]. Finally, HHV-8 has also been shown to cause Kaposi sarcoma in HIV positive patients, Africans in the central Africa region, and individuals from the Mediterranean basin [14]. Our network (Midway Specialty Care) consists of 12 practices dedicated to the treatment of HIV positive individuals as well as patients with conditions such as Hepatitis B and C and other infections. We are located throughout Florida. We currently manage approximately 5,400 HIV positive individuals from all strata of society.

We aimed to identify patients who fit the clinical and pathological criteria for multicentric Castleman’s disease [15]. A retrospective chart review was performed in a sample size of 5,400 people living with HIV, consented for treatment. Demographics (ex. age, sex, race, ethnicity, and MSM status), lab data (ex. HIV and HHV-8 viral status), treatment regimen (ex. antiretroviral, chemotherapy) and clinical course were extracted from electronic medical records and clinical charts. Pathology reports were consistent with diagnosis of Castleman’s disease including the hyaline-vascular variant (small hyaline-vascular follicles and capillary proliferation) and plasma-cell variant (large lymphoid follicles separated by sheets of plasma cells). Basic descriptive analysis was used to describe this data.

We found 4 HIV positive patients who fit the pathologic criteria for multicentric Castleman’s disease [15]. Their characteristics are described in Table 1. All were male with a history of sex with other men (MSM) and all showed evidence of HHV-8 viremia at the time of diagnosis. Three of the four patients received chemotherapy, which included rituximab. Rituximab has been shown to be very effective in treating HIV/HHV-8+ MCD [16,17]. Of the three treated patients, remission duration has been 5 to 89 months (Table 2). One patient declined chemotherapy treatment. No developments of lymphoma or deaths occurred during follow up. Lymphoma development has previously been described in multicentric Castleman’s disease.7 All treated patients have regained normal function to date. All patients who received chemotherapy continued HIV treatment during the period of MCD treatment.

Our experience with multicentric Castleman’s disease in HIV/HHV-8+ patients is consistent with the experience reported by others. Our experience also confirms the likely superiority of a regimen containing rituximab in achieving a longer remission in multicentric Castleman’s disease (Table 3) [17-22]. We plan to continue our study of Castleman’s disease in our population to try to understand better its pathophysiology. Limitations of our study include the retrospective review nature of our investigation and a small sample size with potential for selection bias, as well as a short follow up duration.

  1. (1954) CASE records of the Massachusetts General Hospital Weekly Clinicopathological Exercises: Case 40011. N Engl J Med 250: 26-30.
  2. Castleman B, Iverson L, Menendez VP (1956) Localized mediastinal lymphnode hyperplasia resembling thymoma. Cancer 9: 822-30.
  3. Gaba AR, Stein RS, Sweet DL, Variakojis D (1978) Multicentric giant lymph node hyperplasia. Am J Clin Pathol 69: 86-90.
  4. Frizzera G, Banks PM, Massarelli G, Rosai J (1983) A systemic lymphoproliferative disorder with morphologic features of Castleman’s disease. Pathological findings in 15 patients. Am J Surg Pathol 7: 211-31.
  5. Frizzera G, Peterson BA, Bayrd ED, Goldman A (1985) A systemic lymphoproliferative disorder with morphologic features of Castleman’s disease: clinical findings and clinicopathologic correlations in 15 patients. J Clin Oncol 3:1202-16.
  6. Weisenburger DD, Nathwani BN, Winberg CD, Rappaport H (1985) Multicentric angiofollicular lymph node hyperplasia: a clinicopathologic study of 16 cases. Hum Pathol 16: 162-72.
  7. Oksenhendler E, Boutboul D, Fajgenbaum D (2018) The full spectrum of Castleman disease: 273 patients studied over 20 years. Br J Haematol 180: 206-16.
  8. Talat N, Schulte KM (2011) Castleman’s disease: systematic analysis of 416 patients from the literature. Oncologist 16: 1316-24.
  9. Soulier J, Grollet L, Oksenhendler E (1995) Kaposi’s sarcoma-associated herpesvirus-like DNA sequences in multicentric Castleman’s disease. Blood 86: 1276-80.
  10. Boshoff C, Weiss RA (2001) Epidemiology and pathogenesis of Kaposi’s sarcoma-associated herpesvirus. Philos Trans R Soc Lond B Biol Sci 356: 517-34.
  11. Martin JN, Ganem DE, Osmond DH, Page-Shafer KA, Macrae D, et al. (1998) Sexual transmission and the natural history of human herpesvirus 8 infection. N Engl J Med 338: 948-54.
  12. Fajgenbaum DC, van Rhee F, Nabel CS (2014) HHV-8-negative, idiopathic multicentric Castleman disease: novel insights into biology, pathogenesis, and therapy. Blood 123: 2924-33.
  13. Cesarman E, Chang Y, Moore PS, Said JW, Knowles DM (1995) Kaposi’s sarcoma-associated herpesvirus-like DNA sequences in AIDS-related body-cavity-based lymphomas. N Engl J Med 332: 1186-91.
  14. Porter SR, Di Alberti L, Kumar N (1998) Human herpes virus 8 (Kaposi’s sarcoma herpesvirus). Oral Oncol 34: 5-14.
  15. van Rhee F, Stone K, Szmania S, Barlogie B, Singh Z (2010) Castleman disease in the 21st century: an update on diagnosis, assessment, and therapy. Clin Adv Hematol Oncol 8: 486-98.
  16. Bower M, Powles T, Williams S (2007) Brief communication: rituximab in HIV-associated multicentric Castleman disease. Ann Intern Med 147: 836-9.
  17. Gerard L, Berezne A, Galicier L (2007) Prospective study of rituximab in chemotherapy-dependent human immunodeficiency virus associated multicentric Castleman’s disease: ANRS 117 CastlemaB Trial. J Clin Oncol 25: 3350-6.
  18. Corbellino M, Bestetti G, Scalamogna C (2001) Long-term remission of Kaposi sarcoma-associated herpesvirus-related multicentric Castleman disease with anti-CD20 monoclonal antibody therapy. Blood 98: 3473-5.
  19. El-Osta HE, Kurzrock R (2011) Castleman’s disease: from basic mechanisms to molecular therapeutics. Oncologist 16: 497-511.
  20. Marcelin AG, Aaron L, Mateus C (2003) Rituximab therapy for HIV-associated Castleman disease. Blood 102: 2786-8.
  21. Neuville S, Agbalika F, Rabian C, Briere J, Molina JM (2005) Failure of rituximab in human immunodeficiency virus-associated multicentric Castleman disease. Am J Hematol 79: 337-9.
  22. Newsom-Davis T, Bower M, Wildfire A (2004) Resolution of AIDS-related Castleman’s disease with anti-CD20 monoclonal antibodies is associated with declining IL-6 and TNF-alpha levels. Leuk Lymphoma 45: 1939-4.
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