HAbIT Part 3: Human Leukocyte Antigen (HLA) antibodies after red cell transfusion- a randomised controlled trial

INTERVENTION: HLA compatible red cell transfusion. This will be a personalised form of standard of care blood transfusion (as per Australian Patient Blood Management Guidelines), in which the blood donor will be selected to maximise HLA compatibility with the recipient. Selection will involve comparing the donor and recipient HLA types and choosing a donor who is matched as closely as possible with the recipient by HLA antigens and/or by epitope based methods. The red cells will also be irradiated, as is standard of care for red cell transfusions in some settings, but otherwise will not differ from standard of care red cell transfusion. The number of red cell units given to correct the participant's anaemia to the satisfaction of the treating clinical team will comprise a single "transfusion event". In the absence of a satisfactory response, the "transfusion event" will end when 3 days have elapsed after the first unit was transfused. CONDITION: anaemia; ; anaemia Blood ‐ Anaemia Inflammatory and Immune System ‐ Other inflammatory or immune system disorders PRIMARY OUTCOME: The primary outcome is the proportion of patients with de novo blood donor‐specific HLA antibodies following transfusion. Antibody positivity will be defined according to standard Australian Red Cross Blood Service Transplantation and Immunogenetics Services practice, and specificity determined with reference to blood donor HLA typing. An antibody positive in the post‐transfusion sample but not the pre‐transfusion sample will be considered de novo for the purposes of the study. Where participants are transfused with additional compatible red cells, unselected blood cells, or other blood products within 6 weeks of the study transfusion the data will be analysed separately, and an analysis performed that excludes these patients. Additional patients may be recruited if the number of patients in these groups is sufficient to affect the power of an analysis excluding them. Further samples will be collected 6‐8 weeks after the second transfusion event as per standard of care, and these will be part of the separate analysis.; The primary endpoint analysis will compare all 3 groups with individual, paired comparisons. The study will be considered to have met its primary endpoint if the proportion of patients with de novo blood donor‐specific HLA antibodies following transfusion is significantly lower in the HLA compatible group than in either of the other 2 groups, or in the two groups combined.; [ The timepoint for the primary outcome is visit 3, which can occur at any time between 6 and 8 weeks after the transfusion visit (visit 2).] ; [The timepoint for this secondary outcome is visit 3, which can occur at any time between 6 and 8 weeks after the transfusion visit (visit 2).] Incidence of de novo non‐DSA in participants receiving the intervention. De novo non‐DSA will be defined as per de novo DSA, but where antibodies are not directed at donor epitopes. Antibody test results will be assessed by laboratory staff with expertise in HLA antibody test interpretation, who will be blinded to the status of participants.[The timepoint for this secondary outcome is visit 3, which can occur at any time between 6 and 8 weeks after the transfusion visit (visit 2).] INCLUSION CRITERIA: a) Eligible for blood transfusion according to local site clinical guidelines and anticipated to require a red cell transfusion on clinical grounds by participating unit b) Patient assessed as competent to consent and participate c) Transfusion must occur in a hospital setting (including satellite dialysis units) d) Anticipated to be able to provide a further blood sample 6‐8 weeks post‐transfusion e) > 18 years of age f) Not pregnant SECONDARY OUTCOME: Compatibility assessment‐ median HLA compatibility of supplied product by antigen (number of antigens mismatched) and eplet score. [Time of supply.] Incidence of de novo DSA in participants receiving the unselected irradiated red cell units, compared to those receiving unselected non‐irradiated units. Antibody positivity will be defined according to standard Australian Red Cross Blood Service Transplantation and Immunogenetics Services practice, and specificity determined with reference to blood donor HLA typing. An antibody positive in the post‐transfusion sample but not the pre‐transfusion sample will be considered de novo for the purposes of the study. Where participants are transfused with additional compatible red cells, unselected blood cells, or other blood products within 6 weeks of the study transfusion the data will be analysed separately, and an analysis performed that excludes these patients. Additional patients may be recruited if the number of patients in these groups is sufficient to affect the power of an analysis excluding them. Further samples will be collected 6‐8 weeks after the second transfusion event as per standard of care, and these will be part of the separate analysis.