Identification and Treatment of Thrombotic Microangiopathies in Allogeneic Stem Cell Transplants
Status:
Completed
Trial end date:
2018-03-28
Target enrollment:
Participant gender:
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.