Overcoming pre-transfusion testing challenges with dithiothreitol to optimize transfusion support in multiple myeloma patients on daratumumab therapy

Daratumumab (DARA) is a human monoclonal antibody that specifically targets the CD38 protein, which is predominantly expressed in multiple myeloma (MM) cells. However, DARA also binds to CD38 antigens that are sparsely present in red blood cells, leading to difficulties during pre-transfusion testing. It is essential to address DARA’s interference in pre-transfusion testing before proceeding with transfusions. Three MM patients undergoing DARA treatment in our center experienced interference during pre-transfusion testing. The pretransfusion testing included blood grouping, antibody screening, and cross-matching. DARA interference resulted in pan-positive reactions in antibody screening and identification panels and incompatible cross-matches. This interference can mimic high-incidence alloantibodies or warm autoantibodies. To eliminate the interference of DARA in antibody screening, identification, and compatibility testing, we utilized 0.2 M dithiothreitol (DTT) to remove CD38 from both the reagent and donor red blood cells. However, it is important to note that DTT denatures Kell antigens, so these antigens should be typed before treating red cells with this reagent. Effective communication between clinicians and blood transfusion services is crucial before starting DARA treatment to avoid unnecessary workups and delays in transfusion.