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Daratumumab patients positive with DTT treated cells

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Has anyone else come across patients receiving daratumumab where the DTT treated screen is still reactive?  I work at a reference lab in a large hospital with a very large population of multiple myeloma patients and have come across 3 such patients.  We have tested DTT treated panels and usually see panreactivity give or take a cell or 2 every now and then.  In all 3 the plasma was non-reactive with untreated cord cells, autologous cells and red cells from a few other patients receiving dara.  Interestingly when we DTT treated the cord cells, AC and cells from other dara patients, we got positive results.  All 3 had negative DAT's; an eluate was tested on one patient just because and it was negative.  Titration studies with DTT treated cells varied from 8 to 2048.  We did verify that the DTT treated cells were acceptable by testing them with other dara patients, all which resulted in negative screens.  Some commonalities between the patients were they are all older African american females with history of rbc transfusion.  In one scenario the DTT treated screen had been negative until she received a red cell, then her next sample was positive!  All have since been transfused and tolerated the transfusions well.  Any ideas what could be happening...crypt antigen being exposed by the DTT?  I appreciate any input or hearing if anyone else has experienced this.  Thanks : )

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This may be a silly question but are you sure the patient was treated with DARA (CD38)? Could they have received the new CD47 drug that is not neutralized by DTT?

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In which buffer do you resuspend your DTT treated cells? May be these patients do have antibodies against one or several components of this buffer (antibodies against preservatives used in RBC buffer are not so uncommon).

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We store treated cells in Alsever's solution but wash and resuspend them in normal saline for testing.  We have also tested these patients with freshly treated cells that haven't been in Alsever's and still get the reactions.  Thanks for the input.

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