ABO incompatibile graft management in pediatric transplantation

Abstract

Up to 40% of donor-recipient pairs in SCT have some degree of ABO incompatibility, which may cause severe complications. The aim of this study was to describe available options and survey current practices by means of a questionnaire circulated within the EBMT Pediatric Diseases Working Party investigators. Major ABO incompatibility (donor's RBCs have antigens missing on the recipient's cell surface, towards which the recipient has circulating isohemagglutinins) requires most frequently an intervention in case of bone marrow grafts, as immediate or delayed hemolysis, delayed erythropoiesis and pure red cell aplasia may occur. RBC depletion from the graft (82%), recipient plasma-exchange (14%) were the most common practices, according to the survey. Graft manipulation is rarely needed in mobilized peripheral blood grafts. In case of minor incompatible grafts (donor has isohemagglutinins directed against recipient RBC antigens), isohemagglutinin depletion from the graft by plasma reduction/centrifugation may be considered, but acute tolerability of minor incompatible grafts is rarely an issue. According to the survey, minor ABO incompatibility was either managed by means of plasma removal from the graft, especially when isohemagglutinin titer was above a certain threshold, or led to no intervention at all (41%). Advantages and disadvantages of each method are discussed.

Donor‐type red blood cell transfusion to deplete isoagglutinins prior to allogeneic stem cell transplantation from ABO major incompatible bone marrow donors

“…There was no significant difference between the two groups in OS nor EFS in the entire cohort (Figure 3), and TRM in a separate match‐paired analysis in the groups of patients with malignant versus non‐malignant diseases (data not shown). In light of recently published work, 16 we separately investigated the outcomes (OS, EFS and TRM) in recipients with higher (≥16) versus lower (0–8) anti‐donor ABO titres, which were indistinguishable (data not shown).…”

“…Alternative methods for management of ABO major incompatible BM transplantation have been proposed. According to a recent survey of Balduzzi et al 16 for the EBMT Pediatric Working Party, our approach is not a preferred method in the majority of transplant centres, which identified especially RBC depletion from the graft and plasma exchange as most relevant. While both methods are well established and clearly effective with respect to their immediate goal of rendering infusion of the transplant acutely safe and tolerable, both are also associated with relevant disadvantages.…”

“…Different approaches have been taken to overcome ABO blood group disparity: RBC depletion from the graft is the most commonly used approach 16 and a new apheresis‐based technology has reduced CD34+ cell loss 4,17 . It requires relatively large RBC volumes as well as a modest excess of stem cells to compensate for loss during preparation, which may not always be possible to collect. Plasma exchange during the conditioning period allows an in vivo isoagglutinin depletion 18 .…”

Investigation of risk factors associated with erythrocyte engraftment after ABO‐incompatible hematopoietic stem cell transplantation

“…Since various donor sources including cord blood have been used in recent years, the influence of donor sources on ABO‐incompatible HSCT recovery may be of concern. In addition, research on erythropoiesis has shown that ABO incompatibility delays erythrocyte engraftment or presents a risk for developing pure red cell aplasia (PRCA) 2,4,6,8,11,12 . However, the specific types of ABO‐incompatible HSCTs that cause delayed erythrocyte engraftment are not yet fully understood.…”

“…In ABO incompatibility, there are three different patterns—major mismatch, minor mismatch, and bidirectional mismatch—depending on the combination of recipient and donor ABO blood types 1,4,12 . In major mismatch and bidirectional mismatch, an anti‐A/B isoagglutinin directed against the donor's A/B antigen on erythrocyte is present in the recipient 1,4 .…”