ABO- incompatible stem cell transplantation with pre-existing donor specific HLA and red blood cell antibodies

A 63-year-old woman with blood group B RhD ccD.EE received allogenic stem cell transplant (SCT) for myelodysplasia with a 9/10 human leucocyte antigen (HLA) compatible unrelated donor with blood group O RhD CCD.ee. The patient showed pre-existing red blood cell (RBC) antibodies anti-C and anti-e against donor erythrocytes and severe HLA alloimmunization.

HLA antibody screen was performed using Luminex technology and erythrocyte chimerism, titration of RBC-antibodies and direct antiglobulin test (DAT) by standard gel microcolumn agglutination method. Before SCT the patient received Daratumumab, Bortezomib, Dexamethason and immunabsorbation to avoid graft failure and to reduce high titer HLA-antibodies. To avoid panagglutination in the indirect antiglobulin (IAT) test after therapy with Daratumumab, test RBCs were treated with Dithiothreitol. After SCT the patient received irradiated RBC transfusions of blood group O ccD.EE considering the known alloantibodies. The patient received irradiated apheresis platelet concentrates (PC), which were matched for HLA-antibodies with mean fluorescence intensity >5000.

B-cell-depletion, immunosuppression and immunabsorbation significantly reduced intensity of HLA-immunization. After SCT the patient needed a total of 5 PC and 4 RBC units. Before SCT anti-C-titer was 8 and anti-e-titer 1. On day 7 after SCT titers were stable, on day 62 anti-C showed a titer of 1, anti-e could not be detected IAT anymore but DAT was still positive. Elution demonstrated the presence of anti-C and anti-e alloantibodies on donor erythrocytes without evidence of hemolysis. Despite alloimmunization the patient showed fast donor engraftment with reconstitution of leucocytes at day 13 and platelets at day 12. Last RBC transfusion was on day 8. In contrast to leucocyte chimerism reaching 100% at day 28, complete erythrocyte chimerism was still not reached at publication. Donor specific HLA antibodies (HLA-B 62) are no longer detectable until today.

Due to ABO- and rhesus-incompatible- setting with additional presence of donor specific HLA and red blood cell antibodies, this constellation presented a risk transplantation with high requirements in transfusion medicine care and the need for close interdisciplinary collaboration. Despite the pre-existing immunization there was fast donor engraftment, although erythrocytic chimerism was delayed.

There is no conflict of interest.