title: Diagnostic and risk criteria for HSCT-associated thrombotic microangiopathy: a study in children and young adults.
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.
authors.affiliation: Division of Bone Marrow Transplantation and Immune Deficiency.
authors.forename: Sonata
authors.initials: S
authors.lastname: Jodele
authors.affiliation: Division of Bone Marrow Transplantation and Immune Deficiency.
authors.forename: Stella M
authors.initials: SM
authors.lastname: Davies
authors.affiliation: Division of Bone Marrow Transplantation and Immune Deficiency.
authors.forename: Adam
authors.initials: A
authors.lastname: Lane
authors.affiliation: Division of Biostatistics and Epidemiology.
authors.forename: Jane
authors.initials: J
authors.lastname: Khoury
authors.affiliation: Division of Bone Marrow Transplantation and Immune Deficiency.
authors.forename: Christopher
authors.initials: C
authors.lastname: Dandoy
authors.affiliation: Division of Nephrology and Hypertension, and.
authors.forename: Jens
authors.initials: J
authors.lastname: Goebel
authors.affiliation: Division of Bone Marrow Transplantation and Immune Deficiency.
authors.forename: Kasiani
authors.initials: K
authors.lastname: Myers
authors.affiliation: Division of Bone Marrow Transplantation and Immune Deficiency.
authors.forename: Michael
authors.initials: M
authors.lastname: Grimley
authors.affiliation: Division of Bone Marrow Transplantation and Immune Deficiency.
authors.forename: Jack
authors.initials: J
authors.lastname: Bleesing
authors.affiliation: Division of Bone Marrow Transplantation and Immune Deficiency.
authors.forename: Javier
authors.initials: J
authors.lastname: El-Bietar
authors.affiliation: Division of Bone Marrow Transplantation and Immune Deficiency.
authors.forename: Gregory
authors.initials: G
authors.lastname: Wallace
authors.affiliation: Division of Critical Care Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH; and.
authors.forename: Ranjit S
authors.initials: RS
authors.lastname: Chima
authors.affiliation: Division of Critical Care Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH; and.
authors.forename: Zachary
authors.initials: Z
authors.lastname: Paff
authors.affiliation: Division of Nephrology, The Children's Hospital of Philadelphia, Philadelphia, PA.
authors.forename: Benjamin L
authors.initials: BL
authors.lastname: Laskin
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000175:diagnosis* / Q000188:drug therapy / Q000209:etiology* / Q000401:mortality; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D015996:Survival Rate; D057049:Thrombotic Microangiopathies / Q000175:diagnosis* / Q000188:drug therapy / Q000209:etiology* / Q000401:mortality; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents