Impact of Alemtuzumab on Isohaemagglutinin Titres
Research type
Research Study
Full title
Evaluation of ABO isohaemagglutinin titre variability over time and the impact of Alemtuzumab induction therapy on ABO incompatible renal transplants
IRAS ID
160649
Contact name
Alexander Hogan
Contact email
Sponsor organisation
Red Cell Immunohaematology, NHSBT
Duration of Study in the UK
0 years, 5 months, 22 days
Research summary
Transplantation across the ABO barrier is an increasingly common procedure due to the development of effective peri-operative desensitisation therapies which enable patients to receive live donor kidneys which would otherwise be considered unobtainable. Long-term ABO incompatible (ABOi) kidney graft survival is comparable to that of ABO compatible (ABOc) grafts, after the risk of ABO antibody mediated rejection has been overcome (after approximately 14 days) and immune accommodation of the graft occurs, a process which is incompletely understood.
Desensitisation therapy is required to prevent ABO antibody mediated rejection of ABOi grafts by reducing ABO antibody titres to clinically insignificant levels. The efficacy is correlated to patients’ basal ABO titre levels, as the basal level predicts the probability of rebound above the desired titre of 8. At present patients can be enrolled on the ABOi program if their ABO titres are 256 or lower. However, current exclusion protocol is based on a single titre result and there is a paucity of evidence regarding ABO antibody stability over time. The first aim of the study is therefore to identify whether variation does occur. If it were demonstrated that ABO titres showed significant variation over time a protocol revision would be required to prevent inappropriate exclusion of patients.
Whilst there are many protocols for desensitisation, one agent, Alemtuzumab, has come under scrutiny in Newcastle as post-operative ABO antibody titre rebound has occurred in cases when it has been used for induction therapy (n=4), leading to the loss of 3 grafts. Only one ABOi kidney from 36 has been lost when Alemtuzumab has been absent from the therapeutic regimen. Consequently, the second aim of the study is to compare Alemtuzumab efficacy against other therapies for controlling post-transplant ABO antibody titres in patient’s receiving ABOc grafts to establish whether Alemtuzumab influences ABO antibody titre rebound.
REC name
South Central - Berkshire Research Ethics Committee
REC reference
14/SC/1332
Date of REC Opinion
15 Oct 2014
REC opinion
Favourable Opinion