Donor-Specific Isoagglutinin Clearance in ABO Mismatched Stem Cell Transplant Recipients: How Long Should It Normally Take?

Introduction: In patients undergoing ABO-incompatible stem cell transplants, recipient isoagglutinins with specificity for donor antigens are expected to slowly become undetectable during the post-transplant period, presumably secondary to the loss of recipient plasma cells via either conditioning chemotherapy or graft-versus-host-disease. Conversely, the persistence or return of these anti-donor isoagglutinins may induce hemolytic anemia or pure red cell aplasia, and may even signify disease relapse. In order to define the expected time to clearance of these donor isoagglutinins at our institution, a retrospective study was performed

Methods: The transfusion records of all major-side or bidirectionally ABO-incompatible stem cell transplants performed at an academic cancer hospital between May 2009 and July 2018 were reviewed. Patients without detectable anti-donor isoagglutinins at time of transplant were excluded. Isoagglutinin clearance was defined as non-reactivity of patient plasma against donor-type reverse grouping cells occurring during the post-transplant period; relapse was defined as a 2+ or stronger reaction after one or more non-reactive results

Results: A total of 280 patients were included in analysis, of which 44 were native group A, 42 group B and 194 group O. Average age was 52 (±13) years and 130 (46%) were female. Compatibility samples were sent to the UHN blood bank during the post-transplant period for a median of 156 days (IQR 74-370 days). During this time period, donor-targeting/host-derived isoagglutinin clearance was documented in 192 (69%) patients at a median of 48 days (IQR 23-116.5) post-transplant. Of these, 52 (30%) experienced a subsequent return of reactivity at a median 98 days post-transplant (IQR 54-216). Amongst the 128 patients with at least 28 days of post-transplant monitoring and no return of previously cleared isoagglutinins, the median time to clearance was 60 days (IQR 26.5 - 127.5 days). There was no statistically significant difference in time to isoagglutinin clearance between those with and without a subsequent return of reactivity, and time to durable clearance did not correlate with patient age, sex or native ABO group.

Conclusions: Amongst patients undergoing major-side or bidirectionally ABO incompatible stem cell transplants, the majority will have cleared their donor-specific isoagglutinins within 120 days of stem cell infusion, although this does not guarantee against later return of reactivity. Thus, the persistence of donor-specific isoagglutinins beyond 120 days post-transplant, or the subsequent return of previously cleared isoagglutinins, may be considered abnormal results which warrant notification of the clinical team by the hospital transfusion service.