title: New approaches in the diagnosis, pathophysiology, and treatment of pediatric hematopoietic stem cell transplantation-associated thrombotic microangiopathy.
abstract: Hematopoietic stem cell transplantation (HSCT)-associated thrombotic microangiopathy (TA-TMA) is an understudied complication of HSCT that significantly affects transplant-related morbidity and mortality. Over the past several decades, the cause of TA-TMA has remained unknown, limiting treatment options to non-specific therapies adapted from other diseases. Recent prospective studies dedicated to the study of TA-TMA have provided new insights into the pathogenesis of, and genetic susceptibility to TA-TMA, raising awareness of this important transplant complication and allowing for the identification of potentially novel therapeutic targets. Specifically, many patients with TA-TMA develop multi-organ tissue injury through endothelial damage mediated by the activation of the complement pathway, leading to rational therapeutic strategies including complement blockade. This new knowledge has the potential to favorably influence clinical practice and change the standard of care for how patients with TA-TMA are managed. In this review, we summarize novel approaches to the recognition and management of TA-TMA, using case examples to illustrate key clinical points that hopefully lead to improved short and long-term outcomes for these complex HSCT patients, who remain at significant risk for treatment-related morbidity and mortality.
authors.affiliation: Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, OH. Electronic address: sonata.jodele@cchmc.org.
authors.forename: Sonata
authors.initials: S
authors.lastname: Jodele
authors.affiliation: Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Dandoy
authors.affiliation: Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
authors.forename: Kasiani C
authors.initials: KC
authors.lastname: Myers
authors.affiliation: Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
authors.forename: Javier
authors.initials: J
authors.lastname: El-Bietar
authors.affiliation: Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
authors.forename: Adam
authors.initials: A
authors.lastname: Nelson
authors.affiliation: Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
authors.forename: Gregory
authors.initials: G
authors.lastname: Wallace
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; D064591:Allografts; D002648:Child; D002675:Child, Preschool; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007223:Infant; D008297:Male; D057049:Thrombotic Microangiopathies / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology / Q000628:therapy
keywords: Complement; Eculizumab; Hematopoietic stem cell transplant; TA-TMA; Thrombotic microangiopathy