Diagnostic and risk criteria for HSCT-associated thrombotic microangiopathy: a study in children and young adults

Blood. 2014 Jul 24;124(4):645-53. doi: 10.1182/blood-2014-03-564997. Epub 2014 May 29.

Abstract

Transplant-associated thrombotic microangiopathy (TMA) leads to generalized endothelial dysfunction that can progress to multiorgan injury, and severe cases are associated with poor outcomes after hematopoietic stem cell transplantation (HSCT). Identifying patients at highest risk for severe disease is challenging. We prospectively evaluated 100 consecutive HSCT recipients to determine the incidence of moderate and severe TMA and factors associated with poor overall outcomes. Thirty-nine subjects (39%) met previously published criteria for TMA. Subjects with TMA had a significantly higher nonrelapse mortality (43.6% vs 7.8%, P < .0001) at 1 year post-HSCT compared with those without TMA. Elevated lactate dehydrogenase, proteinuria on routine urinalysis, and hypertension were the earliest markers of TMA. Proteinuria (>30 mg/dL) and evidence of terminal complement activation (elevated sC5b-9) in the blood at the time of TMA diagnosis were associated with very poor survival (<20% at 1 year), whereas all TMA subjects without proteinuria and a normal sC5b-9 serum concentration survived (P < .01). Based on these prospective observations, we conclude that severe TMA occurred in 18% of HSCT recipients in our cohort and propose an algorithm to identify the highest-risk patients who might benefit from prompt clinical interventions.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Female
  • Follow-Up Studies
  • Graft vs Host Disease / diagnosis*
  • Graft vs Host Disease / drug therapy
  • Graft vs Host Disease / etiology*
  • Graft vs Host Disease / mortality
  • Hematopoietic Stem Cell Transplantation / adverse effects*
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Male
  • Prognosis
  • Prospective Studies
  • Risk Factors
  • Survival Rate
  • Thrombotic Microangiopathies / diagnosis*
  • Thrombotic Microangiopathies / drug therapy
  • Thrombotic Microangiopathies / etiology*
  • Thrombotic Microangiopathies / mortality
  • Transplantation, Homologous
  • Young Adult

Substances

  • Immunosuppressive Agents