Implementation of soluble CD38 in blood crossmatching for patients on anti‐ CD38 therapy: A single‐center experience

BACKGROUND: Human monoclonal (MoAb) anti-CD38 antibodies, such as daratumumab, are used to treat diseases such as multiple myeloma. Because red blood cells (RBCs) express CD38, these MoAbs interfere with antibody screening and crossmatching in blood banks. The dithiothreitol (DTT) treatment of reagent cells to destroy CD38, combined with phenotyping/genotyping, has been used to address this interference. Due to anti-CD38 activity in the patient's plasma, RBC units will be crossmatch incompatible and labeled crossmatch-incompatible, necessitating communication with the ordering team regarding the safety of blood transfusion. The recombinant soluble CD38 (sCD38) antigen neutralizes the MoAb in a patient's plasma and can be used to perform crossmatches. Here, we describe our experience with sCD38 in RBC crossmatching. STUDY DESIGN AND METHOD: We began using sCD38 (Grifols) for RBC crossmatching in January 2026 (using 6 μL of sCD38 per crossmatch) following completion of a validation study. Because of the known interference of sCD38 with the Duffy blood group system (by denaturation), its use was limited to RBC crossmatching. We use the DTT method for antibody screening tests. RESULTS: A total of 128 RBC crossmatches were performed for 49 patients on daratumumab. The sCD38 neutralized daratumumab in all crossmatching samples. Thus, all units were labeled crossmatch-compatible, eliminating the need for provider communication. At the last follow-up, with type and screen for these patients, no new alloantibody was detected. CONCLUSION: Soluble CD38 neutralized the anti-CD38 MoAb, enabling crossmatch-compatible RBC units to be issued and obviating the need to notify the provider of apparent incompatibility.