Extended Rhesus and Kell Phenotype-Matched Red Blood Cell (RBC) Transfusions Reduce RBC Alloimmunization and RBC Transfusion Burden in Patients with Myeloid Neoplasm
Authors: Spooner Michaela , Yu Joanne , Wiseman Thomas , Toop Carla , Khanna Shreyas , Kok Chung How , Hiwase Devendra 
Published: December 2024

Background: Up to 90% of patients with myelodysplastic syndrome (MDS) require red blood cell (RBC) transfusions and 11-14% of RBC-transfused patients develop RBC alloantibodies (Singhal et al., Haematologica 2017; Chhetri et al., Haematologica 2019), most commonly against Rhesus (Rh) and Kell (K). RBC alloimmunisation can trigger RBC autoantibody formation which, in turn, can lead to bystander hyperhaemolysis of autologous RBC and increases RBC transfusion requirements.
Method: Patients with primary MDS and acute myeloid leukemia (AML) enrolled in the SA Myeloid Neoplasm registry with at least ≥3 months follow up, for whom RBC phenotype information was available, were included for further analysis. The frequency of Rh and K phenotype-mismatched RBC transfusions and RBC alloimmunization rate following Rh and K phenotype-matched and -mismatched transfusions were evaluated. We subsequently compared the pattern of RBC alloantibodies between the two groups and assessed the impact of alloimmunization on RBC autoantibody formation and RBC transfusion burden.
Results: Extended Rh and K RBC phenotype was available for 450 myeloid neoplasm (MN) patients. The median age was 75 years (interquartile range 67, 83) and 172 (38.2%) patients were female. The majority of patients had MDS (n=333, 74%), followed by AML (n=114, 25.3%) and other related MN (n=3; 0.7%)
During the study, 408 (90.7%) patients required 19,720 units of RBC transfusions, and 71 (17.2%) patients developed 106 clinically significant alloantibodies. The most prevalent antibodies were against antigen E (n=29, 40.8%), D (n=14, 19.7%), C (n=13, 18.3%), Jka (n=7, 9.9%), K (n=5; 7.0%), S (n=3, 4.2%), Fya (n=3, 4.2%) and Jkb (n=2, 2.8%).
Patients were categorized into three groups based on exposure to Rh or K phenotype-matched RBC transfusions: patients who always received Rh and K phenotype-matched RBC units at our state-wide pathology service (matched group; n=31), patients who received at least one mismatched RBC transfusion (mismatch group; n=211), and patients who received RBC units without information about donor unit phenotype (unknown donor phenotype group; n=157).
Four (12.9%) patients in the phenotype-matched group developed eight alloantibodies against Jka (n=2), S (n=2), D (n=1), C (n=1) and E (n=2). This group comprised one female patient with pre-existing antibodies against D and C prior to RBC transfusions at our service, likely due to prior pregnancy or transfusion at another centre, who subsequently developed antibody against Jka. Another male patient developed anti-E following platelet transfusion.
In the mismatched group, 34 (16.1%) patients developed 44 RBC alloantibodies, primarily towards antigen E (n=9), C (n=5), K (n=4) and D (n=4). The highest rate was observed in the unknown donor phenotype group, with 33 (21.01%) patients developing RBC alloantibodies towards antigen E (n=18), D (n=9), C (n=7) and Jka (n=3).
Having observed a higher RBC alloimmunization rate, we evaluated its clinical impact. The RBC autoimmunization rate was significantly higher in RBC-alloimmunized patients compared to those without RBC alloimmunization (21.1% vs. 1.8%; P &lt;0.0001). Importantly, RBC transfusion requirement was significantly higher in alloimmunized compared to non-alloimmunized patients (65.2 ± 113.7 vs. 44.7 ± 54.0; P=0.03). In RBC-alloimmunized patients (n=71), RBC transfusion requirement was significantly increased following RBC alloimmunization compared to pre-alloimmunization (15.8 ± 26.9 vs. 48.5 ± 96.6; P&lt;0.0001). Furthermore, the presence of an autoantibody was associated with a significant increase in RBC transfusion requirement in alloimmunized patients (22.3 ± 48.8 vs. 87.3 ± 120.7; P=0.001).
Conclusion: One in six RBC-transfused MDS and AML patients are at risk of RBC alloimmunization, which is associated with RBC autoantibody formation and increased transfusion requirements. Rh and K phenotype-matched RBC transfusions reduce the risk of alloimmunization and autoimmunization. Our study provides compelling evidence to provide Rh and K phenotype-matched transfusions.