Alloimmunization to RhD antigen in RhD-incompatible haemopoietic cell transplants with non-myeloablative conditioning

Following exposure to RhD antigen, anti-D develops in up to 20% of RhD-negative patients on chemotherapy, but seldom in the recipients of haemopoietic cell (HC) or solid-organ transplants. Data on anti-D formation come from HC transplants using myeloablative conditioning; no data are available for the non-myeloablative HC transplants. The two types of transplant have a distinct isohaemagglutinin disappearance rate and different kinetics of post-transplant red-cell engraftment. The objective of the study was to analyse anti-D formation in patients receiving non-myeloablative transplants from RhD-incompatible donors.

Sixteen patients were analysed: nine RhD-negative recipients of RhD-positive haemopoietic cells; and seven RhD-positive recipients of a graft from a RhD-negative donor. Patients were sequentially tested for irregular antibodies, as well as donor/recipient chimerism by cytogenetics and analysis of DNA variable-number tandem repeats.

Despite having received 7-499 ml of D-positive red cells, none of the RhD-negative recipients developed anti-D. The median follow-up was 202 days. By contrast, anti-D was identified in one of seven RhD-positive recipients of an RhD-negative graft.

Non-myeloablative conditioning containing fludarabine and/or Campath 1H, with cyclosporin A given post-transplant, effectively prevents anti-D formation in RhD-negative recipients of a RhD-positive graft. However, anti-D developed in an RhD-positive recipient of an RhD-negative graft, who was also exposed to RhD-positive blood products before and after the transplant. Transfusion of RhD-positive products should be avoided in such patients.