Contributions
Abstract: PB2526
Type: Publication Only
Background
Daratumumab is a monoclonal antibody (mAb) antiCD38, which is used in the treatment of patients with multiple myeloma. It binds to CD38, which multiple myeloma cells overexpress. Therefore, the plasma of these patients reacts with the red blood cells (RBCs) producing a panreactivity and interfering in the transfusion compatibility testing. Plasma of patients treated with daratumumab agglutinate in the Indirect Antiglobulin Test in all potentiating reagents that accelerates antibody coating on the red cells and this reaction may persist for up to 6 months after the treatment has ended.
Aims
To validate the procedure to resolve the interference of daratumumab in transfusion compatibility testing using red cells treated with Dithiothreitol (DTT), which will allow us to identify a clinically significant antibody that has been initially masked by the presence of daratumumab.
Methods
The study has been conducted in 8 patients diagnosed with multiple myeloma who have been treated with daratumumab in monotherapy. Irregular antibody screening tests and CrossMatching were performed on all of them, being positive in the 6 cases with active treatment, and negative in the 2 in which more than six months have passed since its finalisation. We performed the technique to eliminate reactivity by treating the red cells used in compatibility tests with DTT, which negates the binding of daratumumab to CD38 on the RBC surface, but it also denatures Kell antigens , while preserving the E antigen. The material used was phosphate buffered saline (PBS) (pH 8.0), 0.2 M DTT, cells for Irregular antibody screening tests, K + and E + control cells, monospecific reagent AntiIgG and AntiIgGC3d polyspecific. We performed the method in tubes, Biovue Column Agglutination Technology and Micro Typing System (Bio-Red).
Results
After performing the technique, we were able to eliminate panreactivity in both Irregular antibody screening tests and CrossMatching. Therefore, we consider it a very useful technique to resolve interferences produced by daratumumb with blood compatibility testing. After the treatment with DTT, Kell antigen disappears.
Conclusion
DARA causes pan reactivity in vitro by binding to CD38 on reagent RBCs. It is necessary to do a baseline antibody screen and Rh and Kell phenotyping (type and screen) before starting the treatment with daratumumab. Treating reagent RBCs with DTT is a useful method to mitigate the interference created by antiCD38 mAbs in pretransfusion testing, although it is not free from limitations that, in some cases, may compromise transfusion safety. Treatment with DTT leads to denaturation of the Kell protein, so that antiKell antibodies cannot be identified when the target red cells have been previously treated with DTT. It is not always possible to have RBCs of the same phenotype. We believe that it is essential to have a validated technique to resolve these discrepancies.
Session topic: 32. Transfusion medicine
Keyword(s): Myeloma, transfusion
Abstract: PB2526
Type: Publication Only
Background
Daratumumab is a monoclonal antibody (mAb) antiCD38, which is used in the treatment of patients with multiple myeloma. It binds to CD38, which multiple myeloma cells overexpress. Therefore, the plasma of these patients reacts with the red blood cells (RBCs) producing a panreactivity and interfering in the transfusion compatibility testing. Plasma of patients treated with daratumumab agglutinate in the Indirect Antiglobulin Test in all potentiating reagents that accelerates antibody coating on the red cells and this reaction may persist for up to 6 months after the treatment has ended.
Aims
To validate the procedure to resolve the interference of daratumumab in transfusion compatibility testing using red cells treated with Dithiothreitol (DTT), which will allow us to identify a clinically significant antibody that has been initially masked by the presence of daratumumab.
Methods
The study has been conducted in 8 patients diagnosed with multiple myeloma who have been treated with daratumumab in monotherapy. Irregular antibody screening tests and CrossMatching were performed on all of them, being positive in the 6 cases with active treatment, and negative in the 2 in which more than six months have passed since its finalisation. We performed the technique to eliminate reactivity by treating the red cells used in compatibility tests with DTT, which negates the binding of daratumumab to CD38 on the RBC surface, but it also denatures Kell antigens , while preserving the E antigen. The material used was phosphate buffered saline (PBS) (pH 8.0), 0.2 M DTT, cells for Irregular antibody screening tests, K + and E + control cells, monospecific reagent AntiIgG and AntiIgGC3d polyspecific. We performed the method in tubes, Biovue Column Agglutination Technology and Micro Typing System (Bio-Red).
Results
After performing the technique, we were able to eliminate panreactivity in both Irregular antibody screening tests and CrossMatching. Therefore, we consider it a very useful technique to resolve interferences produced by daratumumb with blood compatibility testing. After the treatment with DTT, Kell antigen disappears.
Conclusion
DARA causes pan reactivity in vitro by binding to CD38 on reagent RBCs. It is necessary to do a baseline antibody screen and Rh and Kell phenotyping (type and screen) before starting the treatment with daratumumab. Treating reagent RBCs with DTT is a useful method to mitigate the interference created by antiCD38 mAbs in pretransfusion testing, although it is not free from limitations that, in some cases, may compromise transfusion safety. Treatment with DTT leads to denaturation of the Kell protein, so that antiKell antibodies cannot be identified when the target red cells have been previously treated with DTT. It is not always possible to have RBCs of the same phenotype. We believe that it is essential to have a validated technique to resolve these discrepancies.
Session topic: 32. Transfusion medicine
Keyword(s): Myeloma, transfusion