Abstract

Background - Transfusion medicine is facing new challenges from therapies which interfere with pre-transfusional tests, such as monoclonal antibodies targeting blood-cell antigens. Anti-CD38 monoclonal antibodies, widely used to treat multiple myeloma, cause panreactivity of indirect antiglobulin test; this can be resolved by treating cells with dithiothreitol to disrupt the CD38 disulphide bonds expressed on red blood cell surfaces. Interference mitigation strategy with dithiothreitol, however, has some drawbacks: it entails losing the traceability of results and the denaturation of blood group systems sensitive to reducing agents; it takes time to perform and quality controls are lost.
Materials and methods - Panels were treated with 0.2 mol/L dithiothreitol and stored for 30 days with a commercial preservative solution. On day 30, we measured the hemolysis indices and ability to eliminate daratumumab and isatuximab interference in the treated cells using indirect antiglobulin test. We also tested the stability of erythrocyte antigenic structure by screening 42 samples with known antibodies; tests were repeated on day 1, 7, 15 and 30. All indirect antiglobulin testing was performed on gel card.
Results - After 30 days from treatment, panels preserved in preservative solution showed hemolysis indices comparable to untreated panels: all cases of interference by anti-CD38 in pre-transfusional tests were successfully mitigated. All antibodies were detected after 30 days, except for KEL system antibodies, as expected, although there was a detectability of anti-Kell antibodies in high titer samples (the first detection in dithiothreitol-treated cells since 1983).
Discussion - We propose the Extended Lifetime Protocol; a simple card-based method which is cheap and traceable, that combines the strengths of anti-CD38 mitigation strategies. It makes it possible to treat and store, at the same time, a sufficient volume of red blood cells, that can be used for the following 30 days, to avoid any delay in transfusional requests.

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Authors

Erica Maiorana - Transfusion Medicine Department, ULSS 8 Berica, Vicenza, Italy

Maria Bortolati - Transfusion Medicine Department, ULSS 8 Berica, Vicenza, Italy

Steluta Croitoru - Transfusion Medicine Department, ULSS 8 Berica, Vicenza, Italy

Gledis Llanaj - Transfusion Medicine Department, ULSS 8 Berica, Vicenza, Italy

Cinzia Ongaro - Transfusion Medicine Department, ULSS 8 Berica, Vicenza, Italy

Eva Polga - Transfusion Medicine Department, ULSS 8 Berica, Vicenza, Italy

Melissa Salvo - Transfusion Medicine Department, ULSS 8 Berica, Vicenza, Italy https://orcid.org/0000-0002-0111-2712

Alessandra Sandini - Transfusion Medicine Department, ULSS 8 Berica, Vicenza, Italy

Krizia Succoli - Transfusion Medicine Department, ULSS 8 Berica, Vicenza, Italy

Tiziana Tortomasi - Transfusion Medicine Department, ULSS 8 Berica, Vicenza, Italy

Giacomina Vicino - Transfusion Medicine Department, ULSS 8 Berica, Vicenza, Italy

Francesco Fiorin - Transfusion Medicine Department, ULSS 8 Berica, Vicenza, Italy https://orcid.org/0000-0003-0856-0064

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