Eculizumab to Treat Thrombotic Microangiopathy/Atypical Hemolytic Uremic Syndrome -Associated Multiple Organ Dysfunction Syndrome in Hematopoietic Stem Cell Transplant Recipients
Eculizumab to Treat Thrombotic Microangiopathy/Atypical Hemolytic Uremic Syndrome -Associated Multiple Organ Dysfunction Syndrome in Hematopoietic Stem Cell Transplant Recipients
Hematopoietic stem cell transplantation (HCT)-associated thrombotic microangiopathy (TMA) is
 an understudied complication of HCT that significantly affects transplant related morbidity
 and mortality. The investigators hypothesize that early intervention with complement blocker
 eculizumab will double survival in HCT recipients with high risk TMA, as compared to
 historical untreated controls. An optimal eculizumab dosing schedule can be determined for
 this population through eculizumab pharmacokinetic/pharmacodynamic (PK/PD) testing.
This clinical trial is a prospective single arm multi-institution study in children and young
 adults undergoing allogeneic or autologous hematopoietic stem cell transplantation who will
 receive early therapy with eculizumab to prevent TMA-associated MODS after transplantation.
 The purpose of this research study is to examine efficacy of complement blocker eculizumab in
 HCT recipients with high risk TMA and to determine optimal eculizumab dosing regimen for HCT
 recipients with TMA using PK/PD studies. All patients will receive therapy based on their
 weight for 24 weeks. Survival will be assessed at 6 months from TMA diagnosis.
Inclusion Criteria:

 -  Patients of any age undergoing allogeneic or autologous HCT

 -  Histologic TMA diagnosis OR clinical TMA diagnosis and presenting with high risk
 disease features including elevated plasma sC5b-9 above laboratory normal value
 (≥244ng/ml) and proteinuria measured as ≥30mg/dL of protein on random urinalysis x2 or
 protein/creatinine ratio ≥1mg/mg or patient receiving renal replacement therapy.

 -  Minimum weight of ≥ 5kg.

 Exclusion Criteria:

 -  Known hypersensitivity to any constituent of the study medication.

 -  Subjects with unresolved serious Neisseria meningitides infection or progressive
 severe infection.

 -  Patients with diagnosis of TTP as defined by ADAMST13 activity test <10%.

 -  Patients previously treated with eculizumab or other complement blocker for TMA within
 the 60 days prior to first dose of study treatment.