Combined anti-CD20 and mTOR inhibition with factor VIII for immune tolerance induction in hemophilia A patients with refractory inhibitors.

ABSTRACT:

Background

Hemophilia A (HA) inhibitor patients that fail traditional immune tolerance induction (ITI) have increased morbidity and mortality. Preclinical studies support factor VIII (FVIII) tolerance induction with a combined approach of anti-CD20 mediated transient B cell depletion and rapamycin mediated regulatory T cell (Treg) induction.

Methods

Two refractory HA inhibitor patients were treated with rituximab, rapamycin, and FVIII ITI. Their clinical course, anti-FVIII immunoglobulins, cytokines, and select lymphocytes were followed.

Results

One patient achieved complete and the other partial FVIII tolerance; both had marked annualized bleeding rate improvement. FVIII-specific immunoglobulins, but not total Treg counts, correlated with tolerance induction. IL-6 an

SUBMITTER: Doshi BS 

PROVIDER: S-EPMC7888210 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature