Resolving Daratumumab-Induced Serologic Interference: A Modified Low-Concentration DTT Protocol in Multiple Myeloma Patients in Eastern India.

PURPOSE: Daratumumab (DARA), an anti-CD38 monoclonal antibody used in multiple myeloma (MM), interferes with pretransfusion testing by binding to CD38 on red blood cells, resulting in pan-reactivity and crossmatch incompatibility. This poses significant transfusion challenges, particularly in resource-limited settings where mitigation strategies are underutilized. This study aimed to evaluate the immunohematological interference caused by DARA and assess the effectiveness of a modified low-concentration dithiothreitol (DTT) protocol in resolving antibody screen pan-reactivity and restoring crossmatch compatibility. METHODS: A retrospective study was conducted on 43 DARA-treated MM patients between 2019 and 2024 at a tertiary care center in Eastern India. Antibody screening, crossmatching, and DTT-treated testing were performed using column agglutination technology. A modified 0.01 M DTT protocol was developed and validated locally to optimize red cell integrity and minimize reagent use. RESULTS: All patients showed positive antibody screens, with 97.7% exhibiting pan-reactivity and AHG crossmatch incompatibility. DTT treatment resolved reactivity in all cases, with crossmatch compatibility achieved in 42 patients (97.7%). One anti-E alloantibody was identified. A total of 79 red cell units were transfused (mean: 1.84 units/patient), yielding a mean hemoglobin rise of 0.99 g/dL. One mild transfusion reaction occurred. The average turnaround time for DTT processing was 125.9 min. CONCLUSION: This study demonstrates that a modified low-concentration DTT protocol effectively neutralizes DARA-induced interference while preserving red cell integrity. The method is feasible, cost-efficient, and safe for implementation in Indian transfusion services, supporting improved transfusion management in DARA-treated patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at https://doi.org/10.1007/s12288-025-02174-w.