Eculizumab therapy in children with severe hematopoietic stem cell transplantation-associated thrombotic microangiopathy

Biol Blood Marrow Transplant. 2014 Apr;20(4):518-25. doi: 10.1016/j.bbmt.2013.12.565. Epub 2013 Dec 25.


We recently observed that dysregulation of the complement system may be involved in the pathogenesis of hematopoietic stem cell transplantation-associated thrombotic microangiopathy (HSCT-TMA). These findings suggest that the complement inhibitor eculizumab could be a therapeutic option for this severe HSCT complication with high mortality. However, the efficacy of eculizumab in children with HSCT-TMA and its dosing requirements are not known. We treated 6 children with severe HSCT-TMA using eculizumab and adjusted the dose to achieve a therapeutic level >99 μg/mL. HSCT-TMA resolved over time in 4 of 6 children after achieving therapeutic eculizumab levels and complete complement blockade, as measured by low total hemolytic complement activity (CH50). To achieve therapeutic drug levels and a clinical response, children with HSCT-TMA required higher doses or more frequent eculizumab infusions than currently recommended for children with atypical hemolytic uremic syndrome. Two critically ill patients failed to reach therapeutic eculizumab levels, even after dose escalation, and subsequently died. Our data indicate that eculizumab may be a therapeutic option for HSCT-TMA, but HSCT patients appear to require higher medication dosing than recommended for other conditions. We also observed that a CH50 level ≤ 4 complement activity enzyme units correlated with therapeutic eculizumab levels and clinical response, and therefore CH50 may be useful to guide eculizumab dosing in HSCT patients as drug level monitoring is not readily available.

Keywords: CH50; Eculizumab; Eculizumab pharmacokinetics; Hematopoietic stem cell transplant; Thrombotic microangiopathy.

MeSH terms

  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Child
  • Child, Preschool
  • Complement Hemolytic Activity Assay
  • Complement Inactivating Agents / therapeutic use*
  • Complement Membrane Attack Complex / antagonists & inhibitors*
  • Drug Administration Schedule
  • Drug Dosage Calculations
  • Drug Monitoring
  • Hematologic Neoplasms / immunology
  • Hematologic Neoplasms / mortality
  • Hematologic Neoplasms / pathology
  • Hematologic Neoplasms / therapy*
  • Hematopoietic Stem Cell Transplantation / adverse effects*
  • Humans
  • Severity of Illness Index
  • Survival Analysis
  • Thrombotic Microangiopathies / drug therapy*
  • Thrombotic Microangiopathies / etiology
  • Thrombotic Microangiopathies / immunology
  • Thrombotic Microangiopathies / mortality
  • Transplantation, Autologous
  • Transplantation, Homologous


  • Antibodies, Monoclonal, Humanized
  • Complement Inactivating Agents
  • Complement Membrane Attack Complex
  • eculizumab