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A pilot trial of complement inhibition using eculizumab to overcome platelet transfusion refractoriness in human leukocyte antigen allo‐immunized patients
Author(s) -
Vo Phuong,
Purev Enkhtsetseg,
West Kamille A.,
McDuffee Emily,
Worthy Tatyana,
Cook Lisa,
Hawks Geri,
Wells Brian,
Shalabi Reem,
Flegel Willy A.,
Adams Sharon D.,
Reger Robert,
Aue Georg,
Tian Xin,
Childs Richard
Publication year - 2020
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.16385
Subject(s) - eculizumab , medicine , platelet , platelet transfusion , refractory (planetary science) , refractory period , immunology , human leukocyte antigen , antibody , antigen , complement system , astrobiology , physics
Summary Heavily transfused patients frequently develop human leukocyte antigen (HLA) allo‐immunization resulting in platelet transfusion refractoriness and a high risk for life‐threatening thrombocytopenia. Data suggest complement activation leading to the destruction of platelets bound by HLA allo‐antibodies may play a pathophysiologic role in platelet refractoriness. Here we conducted a pilot trial to investigate the use of eculizumab, a monoclonal antibody that binds and inhibits C5 complement, to treat platelet transfusion refractoriness in allo‐immunized patients with severe thrombocytopenia. A single eculizumab infusion was administered to 10 eligible patients, with four (40%) patients overcoming platelet refractories assessed measuring the corrected platelet count increment (CCI) 10–60 min and 18–24 h post transfusion. Responding patients had a reduction in the requirement for subsequent platelet transfusions and had higher post‐transfusion platelet increments for 14 days following eculizumab administration. Remarkably, three of the four responders met CCI criteria for response despite receiving HLA‐incompatible platelets. Our results suggest that eculizumab has the ability to overcome platelet transfusion refractoriness in patients with broad HLA allo‐immunization. This study establishes proof of principle that complement inhibition can treat platelet transfusion refractoriness, laying the foundation for a large multicentre trial to assess the overall efficacy of this approach (ClinicalTrials.gov, identifier: NCT02298933).