Red cell alloimmunization is associated with development of autoantibodies and increased red cell transfusion requirements in myelodysplastic syndrome

Abstract

Up to 90% of patients with a myelodysplastic syndrome require red blood cell transfusion; nevertheless, comprehensive data on red cell alloimmunization in such patients are limited. This study evaluates the incidence and clinical impact of red cell alloimmunization in a large cohort of patients with myelodysplastic syndrome registered in the statewide South Australian-MDS registry. The median age of the 817 patients studied was 73 years, and 66% were male. The cumulative incidence of alloimmunization was 11%. Disease-modifying therapy was associated with a lower risk of alloimmunization while alloimmunization was significantly higher in patients with a revised International Prognostic Scoring System classification of Very Low, Low or Intermediate risk compared to those with a High or Very High risk (P=0.03). Alloantibodies were most commonly directed against antigens in the Rh (54%) and Kell (24%) systems. Multiple alloantibodies were present in 49% of alloimmunized patients. Although 73% of alloimmunized patients developed alloantibodies during the period in which they received their first 20 red cell units, the total number of units transfused was significantly higher in alloimmunized patients than in non-alloimmunized patients (90±100 versus 30±52; P<0.0001). In individual patients, red cell transfusion intensity increased significantly following alloimmunization (2.8±1.3 versus 4.1±2.0; P<0.0001). A significantly higher proportion of alloimmunized patients than non-alloimmunized patients had detectable autoantibodies (65% versus 18%; P<0.0001) and the majority of autoantibodies were detected within a short period of alloimmunization. In conclusion, this study characterizes alloimmunization in a large cohort of patients with myelodysplastic syndrome and demonstrates a signficant increase in red cell transfusion requirements following alloimmunization, most probably due to development of additional alloantibodies and autoantibodies, resulting in subclinical/clinical hemolysis. Strategies to mitigate alloimmunization risk are critical for optimizing red cell transfusion support.

Type 1 IFN signaling critically regulates influenza‐induced alloimmunization to transfused KEL RBCs in a murine model

“…Only a fraction of human RBC transfusion recipients will ever form alloantibodies after transfusion or pregnancy . In fact, fewer than 3% to 5% of all transfused patients will become alloimmunized, with more than 10% of transfused patients with myelodysplastic syndrome and up to 30% to 50% of transfused patients with sickle cell disease becoming alloimmunized. The reasons for the differences in alloantibody prevalence rates are not fully understood, but recipient variables likely contribute.…”

Adverse transfusion reactions in patients with aplastic anaemia or myelodysplastic syndromes

“…Singhal et al . also observed that the total number of RBC units transfused in the alloimmunized patients was higher than in non‐alloimmunized patients (90 ± 100 vs. 30 ± 52; P < 0·0001). Furthermore, transfusion intensity (number of RBC units transfused per month) was significantly higher following RBC alloimmunization (2·8 ± 1·3 vs. 4·1 ± 2·0 units per month; P < 0·0001).…”

“…In another study, Singhal et al . observed that in 817 patients with MDS, the incidence of RBC alloimmunization was 11·0%. These anti‐RBC antibodies were directed against antigens of the RH (Rhesus) (54·0%) and KEL (Kell) (24·0%) blood group systems.…”

Time interval between antibody investigations among patients who demonstrate serial red cell antibody formation

“…Our results are consistent with prior studies. A recent study of RBC alloimmunization rates and transfusion requirements in a large cohort of patients with myelodysplastic syndrome found that one‐half of alloimmunized patients have multiple alloantibodies and that the number of units transfused in these patients was significantly higher than among nonalloimmunized patients . Individual alloimmunized patients were also found to have increased numbers of RBC transfusions following alloimmunization.…”