Red blood cell immunization as an independent predictor of survival in the myelodysplastic syndromes

Despite red blood cell (RBC) immunization being a frequent complication of chronic transfusion in myelodysplastic syndromes (MDS), its prognostic significance remains unclear. We analysed 486 transfused patients diagnosed with MDS. Prognostic impact of RBC immunization (allo- or autoantibodies) was evaluated as a time-dependent covariate. Competing risk methods were applied to estimate the cumulative incidence of immunization. Sixty-nine patients (14.2%) developed RBC immunization, most commonly anti-K and anti-E, which was more frequent in patients transfused before MDS diagnosis (subhazard ratio [SHR]: 2.9, 95% confidence interval [CI]: 1.6-5.4; p = 0.001) and Rh(D)-negative blood group (SHR: 1.9, 95% CI: 1.1-3.2; p = 0.026). RBC immunization was associated with a significant and independent reduction in remaining survival (hazard ratio: 11.9, 95% CI: 7.3-19.6; p = 0.001), without differences between auto- and alloantibodies. RBC immunization was followed by increased transfusion intensity, but transfusion requirements also rose in non-immunized patients over time. RBC immunization did not predict progression to acute myeloid leukaemia (AML). A trend towards fewer new antibodies was observed during hypomethylating therapy. RBC immunization is independently associated with reduced survival in transfusion-dependent patients with MDS, irrespective of AML progression. These findings highlight the potential prognostic relevance of RBC antibodies and call for further investigation into the mechanisms linking immunization, transfusion burden and survival outcomes.