M.A. Marion Posset (Regensburg/ DE), Dr. Andreas Michael Brosig (Regensburg/ DE), Martina Brandl (Regensburg/ DE), Dr. Morad Mohrez (Regensburg/ DE), Dr. Irene Pamler (Regensburg/ DE), Dr. Katharina Kleinschmidt (Regensburg/ DE), Prof. Dr. Selim Corbacioglu (Regensburg/ DE), Prof. Dr. Ralph Burkhardt (Regensburg/ DE), PD Dr. Robert Offner (Regensburg/ DE)
Background
Some blood group alloantibodies develop and persist for life, while others - as the ones subsequently mentioned – typically fall under the detection limit after a few months. Here we report titer progression of alloantibodies anti-FY(a) and anti-Jk(b) in a 26y female patient with sickle cell disease over 16 weeks. During this period the patient received therapy primarily intended for HLA antibody reduction and conditioning chemotherapy (cCTX) before planned allogeneic stem cell transplantation.
Methods
The alloantibodies anti-Fy(a) and anti-Jk(b) - already existing for 2.5 months before initiation of the B-cell- and plasma-depleting immunochemotherapy (iCTX) containing (Rituximab 375mg/m2; Fludarabine 40mg/m2; Dexamethasone 25mg/m2; Velcade 1,3mg/m2) in 02/2023 - were determined automatically using appropriate red cells with the ORTHO VISION® MAX Analyzer (QuidelOrtho). Titer measurements were performed from EDTA plasma at several intermittent time points during the course of 2 cycles of iCTX plus 1 additional dose of Rituximab and during a phase of 8 plasma exchanges (PLX) (8x PLX, means: 1.29-fold plasma volume; 3171mL; 65mL/kg bw) each) before and after each therapy and after cCTX (incl. ATG+Treosulfan).
Results
Antibody titers before initiation of iCTX on 02.02.23 were 1:32 [anti-Fy(a)] and 1:4 [anti-Jk(b)]. After this first cycle, the antibody titers stayed unchanged (16.02.23: anti-Fy(a) 1:32; anti-Jk(b) 1:4). In the period before the 2nd iCTX cycle, anti-Fy(a) was 1:32 and anti-Jk(b) was 1:8 (20.02.23; 09.03.23; 23.03.23). After the 2nd iCTX cycle and a 3rd Rituximab administration on 06.04.23, anti-Fy(a) and anti-Jk(b) remained 1:32 and 1:4, respectively. Finally, after a total of 8 PLX therapies (20.04.23 - 29.04.23), titers dropped from 1:16 to 1:1 [anti-Fy(a)] and 1:8 to negative [anti-Jk(b)], relapsing to 1:16 [anti-Fy(a)] and 1:4 [anti-Jk(b)] after cCTX (09.05.23).
Conclusion
Anti-Fy(a) and anti-Jk(b) proved largely refractory to iCTX over 12 weeks. Only heavily forced antibody-reducing PLX therapy led to a significant reduction by 4 titer levels. Remarkably, even after four PLX therapies, a constant rebound by one titer level was still detectable, which may indicate a high antibody content in tissues or persistence of antibody producing cells. Furthermore, no reducing effect on titer levels was observed in the short term after cCTX.
Offenlegung Interessenkonflikt:
Keine Interessenkonflikte.