Transfusion Reaction and Red Cell Antibody Formation in Allogeneic Hematopoietic Progenitor Cell Transplantation Recipients

Background: Little data exists on the incidence rate of transfusion reactions and red cell antibody formation following allogeneic (allo) hematopoietic progenitor cell transplant (HPCT) recipients.   

Study Design and Methods:  Consecutive related and unrelated Allogeneic HPCTs from 2006 to 2013 were retrospectively reviewed regardless of graft source.  Allo HPCT recipients were analyzed as a whole as well as divided into ABO compatibility groups of identical, minor mismatch, and major/bidirectional mismatch.  Transfusions, transfusion reactions and antibodies were analyzed for the first year post-transplant while survival was recorded throughout the available follow-up period.

Results:  During the study period, 573 patients ranging in age from 0.6 to 72 years underwent first allo HPCT for various malignant and non-malignant etiologies: 278 acute leukemias, 89 lymphomas, 40 multiple myelomas, 134 other hematologic malignancies, 32 non-neoplastic etiologies.  Of these, 52% underwent myeloablative conditioning and 48% reduced intensity conditioning. 

 Transfusion reactions were reported in 93 of the 573 allo HPCT recipients.  The incidence rate of transfusion reactions per 10,000 transfusion episodes was 45.54 in the ABO identical, 61.28 in the minor mismatch, and 29.95 in the major mismatch groups (p=0.04). The most common reaction type reported in all groups was allergic followed by febrile non-hemolytic, transfusion associated circulatory overload, and delayed hemolytic or serologic reactions.  No acute hemolytic, transfusion related acute lung injury (TRALI), post transfusion purpura, transfusion associated graft-versus-host disease, or transfusion associated sepsis reactions were reported.

A total of 43 unique patients(7.5%) developed new antibodies post-transplant: 16 allo HPCT recipients developed clinically significant antibodies, 17 developed clinically insignificant antibodies, and 17 developed auto antibodies post-transplant.  Including those patients with pre-transplant antibodies the overall prevalence of red blood cell antibodies was 14.5%. See Table 1 for incidence rate for forming new rbc antibodies post-transplant.

 

Table 1 – New RBC Antibody Formation Incidence Rate Post-Transplant
ABO Compatibility Group	Clinically Significant Antibody Incidence /10,000 RBC Transfusions	Clinically Insignificant Antibody Incidence/ 10,000 RBC Transfusions,	Auto Antibody Incidence/10,000 RBC Transfusions	Total Antibody Incidence/10,000 RBC Transfusions
Identical	39.33	16.85	39.33	95.51
Minor Mismatch	35.87	57.39	43.04	136.30
Major Mismatch	8.34	16.67	8.34	33.35

A statistically significant difference (p=0.001) was seen in total antibody incidence when comparing the ABO compatibility groups. The most common, clinically significant allo antibodies formed were Anti-E, Anti-Jk^a, Anti-A1, Anti-K, Anti-D, and Anti-C.

Survival of allo HPCT recipients as a whole was not statistically different for those who formed new rbc antibodies post-transplant following adjustment for ABO compatibility, age at transplant, diagnosis, graft source, and pre-transplant rbc infusions (p=0.068).

Allo HPCT recipients that formed new rbc antibodies were not shown to have prolonged engraftment.  Engraftment, neutrophils (ANC) and platelets (PLT), were not statistically different (p=0.34 ANC; p=0.20 PLT) when comparing all allo HPCT recipients to those who formed a new rbc antibody. 

Conclusion:  Transfusion reaction and rbc antibody incidence rates were higher in the ABO minor mismatch when compared to the ABO identical and ABO major mismatch groups.  The reaction etiology (predominantly antibody mediated) and the formation of new antibodies indicates a surprisingly active humoral immune system.   The overall prevalence of antibody formation is likely affected by high exposure to transfusions. Development of a new rbc antibody did not affect engraftment or survival outcomes.