Identification and Treatment of Thrombotic Microangiopathies in Allogeneic Stem Cell Transplants

• Status: Completed
• Trial end date: 2018-03-28
• Target enrollment: 0
• Participant gender: All

Summary

Mortality in the major thrombotic microangiopathies (TMAs), TTP and aHUS, exceeds 90% unless rapidly diagnosed and appropriately treated. TMAs complicate 10-20% of allogeneic bone marrow hematopoietic stem cell transplants (alloHSCT), conveying inferior survival. Multiple etiologies have been proposed for these transplant-associated TMAs (TA-TMAs), but once infection, graft vs. host disease (GvHD), and drug effects have been ruled out, most are treated as TTP-like disorders using plasma exchange (PEx). But PEx has no impact on mortality in this setting. Clear definition of the pathophysiology of the TA-TMAs is required to guide effective treatment. Investigators hypothesize that an aHUS-type TMA, related to dysregulation of the alternative complement pathway, is involved and will be characterized by elevated plasma levels of C5b-9 and detectable C5b-9 deposition in bone marrow sinusoidal vessels. Investigators further hypothesize that treatment with inhibitors of terminal complement components will reverse the TMA in vivo, and block endothelial cell damage in our in vitro model systems. The data investigators generate from this observational study of TA-TMAs should enable prediction of their development prior to overt clinical manifestations, and guide appropriate therapy.

• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Weill Medical College of Cornell University
• Treatments: Eculizumab

Criteria

Inclusion Criteria:

• participants scheduled to undergo an allogeneic stem cell transplant

• willing to consent to genetic testing

Exclusion Criteria:

• pregnant women

• nursing mothers

• women of child-bearing potential who are unwilling to use medically accepted methods of contraception

• patients with known contraindications to use of eculizumab

• patients who cannot tolerate plasma exchange