Advertisement

Treating life-threatening TAFRO syndrome with interleukin-1 inhibition

  • Marco Lanzillotta
    Correspondence
    Corresponding author at: Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), IRCCS-San Raffaele Scientific Institute, via Olgettina 60, 20132, Milan, Italy.
    Affiliations
    Università Vita-Salute San Raffaele, IRCCS San Raffaele Scientific Institute, Milan, Italy

    Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR); IRCCS San Raffaele Scientific Institute, Milan, Italy
    Search for articles by this author
  • Miriam Sant'Angelo
    Affiliations
    Università Vita-Salute San Raffaele, IRCCS San Raffaele Scientific Institute, Milan, Italy

    Pathology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
    Search for articles by this author
  • Naoki Kaneko
    Affiliations
    Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, Japan
    Search for articles by this author
  • Shiv Pillai
    Affiliations
    Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
    Search for articles by this author
  • Maurilio Ponzoni
    Affiliations
    Università Vita-Salute San Raffaele, IRCCS San Raffaele Scientific Institute, Milan, Italy

    Pathology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
    Search for articles by this author
  • Emanuel Della-Torre
    Affiliations
    Università Vita-Salute San Raffaele, IRCCS San Raffaele Scientific Institute, Milan, Italy

    Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR); IRCCS San Raffaele Scientific Institute, Milan, Italy
    Search for articles by this author
Published:February 16, 2021DOI:https://doi.org/10.1016/j.ejim.2021.02.006
      TAFRO syndrome (Thrombocytopenia, Anasarca, Fever, Reticulin fibrosis, and Organomegaly) is a newly recognized variant of idiopathic - human herpesvirus-8 (HHV-8) negative - Multicentric Castleman Disease (iMCD) [
      • Iwaki N
      • Fajgenbaum DC
      • Nabel CS
      • et al.
      Clinicopathologic analysis of TAFRO syndrome demonstrates a distinct subtype of HHV-8-negative multicentric Castleman disease.
      ]. Although salient clinical and histopathological features are similar to most of iMCD related disorders, TAFRO syndrome follows a more aggressive course characterized by rapidly progressive multiorgan failure [
      • Van Rhee F
      • Voorhees P
      • Dispenzieri A
      • et al.
      International, evidence-based consensus treatment guidelines for idiopathic multicentric Castleman disease.
      ]. Due to its recent recognition, standard treatments for TAFRO syndrome are lacking and mostly derived from immunosuppressive regimens used in iMCD including corticosteroids, chemotherapeutic agents (thalidomide and bortezomib), and monoclonal antibodies targeting CD20+ B-lymphocytes (rituximab) or interleukin (IL)-6 (siltuximab and tocilizumab) [
      • Iwaki N
      • Fajgenbaum DC
      • Nabel CS
      • et al.
      Clinicopathologic analysis of TAFRO syndrome demonstrates a distinct subtype of HHV-8-negative multicentric Castleman disease.
      ]. In analogy to iMCD, in fact, TAFRO syndrome seems to be sustained by hyper-activation of innate and adaptive immunity, ultimately leading to hyper-inflammation and organ damage [
      • Angevin E
      • Tabernero J
      • Elez E
      • et al.
      A phase I/II, multiple-dose, dose-escalation study of siltuximab, an anti-interleukin-6 monoclonal antibody, in patients with advanced solid tumors.
      ]. As opposite to iMCD, however, administration of the aforementioned drugs poses relevant safety and efficacy concerns in TAFRO syndrome because thalidomide and IL-6 inhibitors might be detrimental in the context of multiorgan failure, while bortezomib and rituximab might not act as promptly as needed. In addition, TAFRO syndrome appears to be steroid refractory in most cases [
      • Iwaki N
      • Fajgenbaum DC
      • Nabel CS
      • et al.
      Clinicopathologic analysis of TAFRO syndrome demonstrates a distinct subtype of HHV-8-negative multicentric Castleman disease.
      ]. Based on these considerations, we successfully treated a case of TAFRO syndrome with multiorgan failure with IL-1 inhibition.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to European Journal of Internal Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Iwaki N
        • Fajgenbaum DC
        • Nabel CS
        • et al.
        Clinicopathologic analysis of TAFRO syndrome demonstrates a distinct subtype of HHV-8-negative multicentric Castleman disease.
        Am J Hematol. 2016; 91: 220-226
        • Van Rhee F
        • Voorhees P
        • Dispenzieri A
        • et al.
        International, evidence-based consensus treatment guidelines for idiopathic multicentric Castleman disease.
        Blood. 2018; 132: 2115-2124
        • Angevin E
        • Tabernero J
        • Elez E
        • et al.
        A phase I/II, multiple-dose, dose-escalation study of siltuximab, an anti-interleukin-6 monoclonal antibody, in patients with advanced solid tumors.
        Clin Cancer Res. 2014; 20: 2192-2204
        • Della-Torre E
        • Stone JH.
        How I manage" IgG4-Related Disease.
        J Clin Immunol. 2016; 36: 754-763
        • Berti A
        • Della-Torre E
        • Gallivanone F
        • et al.
        Quantitative measurement of 18F-FDG PET/CT uptake reflects the expansion of circulating plasmablasts in IgG4-related disease.
        Rheumatology (Oxford). 2017; 56: 2084-2092
        • Della-Torre E
        • Bozzalla-Cassione E
        • Sciorati C
        • et al.
        A CD8α- Subset of CD4+SLAMF7+ Cytotoxic T Cells Is Expanded in Patients With IgG4-Related Disease and Decreases Following Glucocorticoid Treatment.
        Arthritis Rheumatol. 2018; 70: 1133-1143
        • Sakashita K
        • Murata K
        • Takamori M.
        TAFRO syndrome: current perspectives.
        J Blood Med. 2018; 9: 15-23
        • El-Osta H
        • Janku F
        • Kurzrock R.
        Successful treatment of Castleman's disease with interleukin-1 receptor antagonist (Anakinra).
        Mol Cancer Ther. Jun 2010; 9: 1485-1488
        • Mantovani A
        • Dinarello CA
        • Molgora M
        • Garlanda C.
        Interleukin-1 and Related Cytokines in the Regulation of Inflammation and Immunity.
        Immunity. 2019; 50: 778-795