ABSTRACT
Sensitization is common in pediatric heart transplant candidates and waitlist mortality is high. Transplantation across a positive crossmatch may reduce wait time, but is considered high risk. We prospectively recruited consecutive candidates at eight North American centers. At transplantation, subjects were categorized as nonsensitized or sensitized (presence of ≥1 HLA antibody with MFI ≥1000 using single antigen beads). Sensitized subjects were further classified as complement-dependent cytotoxicity crossmatch (CDC-crossmatch) positive or negative and as donor-specific antibodies (DSA) positive or negative. Immunosuppression was standardized. CDC-crossmatch-positive subjects also received perioperative antibody removal, maintenance corticosteroids, and intravenous immunoglobulin. The primary endpoint was the 1 year incidence rate of a composite of death, retransplantation, or rejection with hemodynamic compromise. 317 subjects were screened, 290 enrolled and 240 transplanted (51 with pretransplant DSA, 11 with positive CDC-crossmatch). The incidence rates of the primary endpoint did not differ statistically between groups; nonsensitized 6.7% (CI: 2.7%, 13.3%), sensitized crossmatch positive 18.2% (CI: 2.3%, 51.8%), sensitized crossmatch negative 10.7% (CI: 5.7%, 18.0%), P = .2354. The primary endpoint also did not differ by DSA status. Freedom from antibody-mediated and cellular rejection was lower in the crossmatch positive group and/or in the presence of DSA. Follow-up will determine if acceptable outcomes can be achieved long-term.
Subject(s)
Blood Grouping and Crossmatching/mortality , Graft Rejection/mortality , HLA Antigens/immunology , Heart Transplantation/adverse effects , Isoantibodies/immunology , Postoperative Complications , Tissue Donors , Adolescent , Child , Child, Preschool , Female , Follow-Up Studies , Graft Rejection/etiology , Graft Survival , Histocompatibility Testing , Humans , Immunosuppression Therapy , Infant , Isoantibodies/blood , Male , Prognosis , Prospective Studies , Risk Factors , Survival RateABSTRACT
BACKGROUND: The impact of donor-recipient ABO matching on outcomes after allogeneic stem cell transplantation has been a matter of controversy. STUDY DESIGN AND METHODS: Individual patient data-based meta-analysis was conducted with a pooled data set provided through six published and one unpublished cohorts. Outcomes in recipients of peripheral blood or bone marrow transplantation for hematologic malignancies were evaluated. A multivariate Cox model was used to adjust differences in outcomes of patients receiving ABO-matched grafts with those receiving major, minor, or bidirectional mismatched grafts. Considering multiple testing, p values of less than 0.05 and 0.001 were considered significant for the primary and secondary endpoints, respectively. RESULTS: In all, 1208 cases, including 697 ABO-matched and 202 major, 228 minor, and 81 bidirectional mismatched transplants, were analyzed. Overall, adverse impact of ABO matching on overall survival (OS), as a primary endpoint, was not observed (adjusted hazard ratios [95% confidence intervals]: major, 1.03 [0.82-1.30], p = 0.81; minor, 1.19 [0.97-1.47], p = 0.10; bidirectional, 1.25 [0.91-1.72], p = 0.17). Among related stem cell recipients, ABO matching had no significant influence on OS, while the minor and bidirectional mismatched groups among unrelated stem cell recipients exhibited lower OS with marginal significance, especially in patients with acute leukemia, patients who received transplants after 1998, and patients who underwent transplants at Asian centers. CONCLUSIONS: Our meta-analysis demonstrates no adverse association between any ABO mismatching and survival. However, marginally lower OS found in recipients of minor or bidirectional mismatched grafts from unrelated donors suggested the need for larger studies focusing on unrelated transplants.