A Heterozygous CFHR3-CFHR1 Gene Deletion in a Pediatric Patient With Transplant-associated Thrombotic Microangiopathy Who was Treated With Eculizumab

J Pediatr Hematol Oncol. 2018 Nov;40(8):e544-e546. doi: 10.1097/MPH.0000000000000986.

Abstract

Complement system dysregulation, such as complement Factor H (CFH) autoantibodies and deletions in CFH-related (CFHR) genes 3 and 1, might cause transplant-associated thrombotic microangiopathy (TA-TMA). The use of eculizumab, a terminal complement inhibitor, could be a targeted therapy for TA-TMA. We report a 1-year-old girl who developed TA-TMA, just after autologous peripheral blood stem cell transplantation in neuroblastoma therapy. Eculizumab improved TA-TMA. Investigation for the complement alternative pathway showed a heterozygous CFHR3-CFHR1 gene deletion, which is involved in complement activation. The patient might develop TA-TMA as a result of complement regulatory gene mutation.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal, Humanized / administration & dosage*
  • Autografts
  • Blood Proteins / genetics*
  • Complement C3b Inactivator Proteins / genetics*
  • Female
  • Gene Deletion*
  • Heterozygote
  • Humans
  • Infant
  • Neuroblastoma* / genetics
  • Neuroblastoma* / therapy
  • Stem Cell Transplantation / adverse effects*
  • Thrombotic Microangiopathies* / drug therapy
  • Thrombotic Microangiopathies* / etiology
  • Thrombotic Microangiopathies* / genetics

Substances

  • Antibodies, Monoclonal, Humanized
  • Blood Proteins
  • CFHR1 protein, human
  • CFHR3 protein, human
  • Complement C3b Inactivator Proteins
  • eculizumab