An epitope-based approach of HLA-matched platelets for transfusion: a noninferiority crossover randomized trial

Abstract

Platelet transfusion refractoriness results in adverse outcomes and increased healthcare costs. Managing refractoriness due to HLA alloimmunization necessitates the use of HLA antigen matched platelets, but requires a large platelet donor pool, and does not guarantee full matching. We report the first ever randomized, double-blind, non-inferiority, cross-over trial comparing HLA epitope-matched (HEM) platelets with HLA standard antigen-matched (HSM) platelet transfusions. Eligibility criteria were alloimmunized, platelet refractory, thrombocytopenic patients with aplastic anemia, myelodysplastic syndrome or acute myeloid leukemia. HEM platelets were selected using HLAMatchMaker epitope (specifically eplet) matching. Patients received up to eight prophylactic HEM and HSM transfusions provided in random order. Primary outcome was one-hour post transfusion platelet count increment (PCI). 49 patients were randomized at 14 UK hospitals. For intention-to-treat, number of evaluable transfusions was 107 and 112 for HEM and HSM, respectively. Unadjusted mean (SD) PCI for HEM and HSM was 23.9 (15) and 23.5 (14.1) respectively (adjusted mean difference -0.1, 95% CI -2.9, 2.8). As the lower limit of 95% CI was not greater than pre-defined non-inferiority limit, HEM was declared non-inferior to HSM. There were no differences in secondary outcomes of platelet counts, transfusion requirements and bleeding events. Adequate one-hour PCI was more frequently observed with a mean number of 3.2 of epitope mismatches compared to 5.5 epitope mismatches for inadequate one-hour increments. For every additional one epitope mismatch, the likelihood of an adequate PCI decreased by 15%. Epitope matched platelets should be considered to support HLA alloimmunized patients. Funded by NHS Blood and Transplant, ISRCTN23996532.

Hemostatic Effect of Related Donor Platelet Transfusion: A Retrospective Cohort Study

“…Although depletion of leukocytes in platelet components has been reported in recent years to prevent the development of HLA alloimmunity 20 , or treatment of platelets with ultraviolet beta or gamma irradiation is also an effective method to prevent the development of HLA alloimmunity 21 , methods of an epitopebased approach of HLA-matched platelets for transfusion reduced Matching di culty 22 . However, on the one hand, these methods increase the work intensity and increase the cost.…”

Association of Protective HLA-A With HLA-B∗27 Positive Ankylosing Spondylitis

“…In the case of AS, the compensatory mechanism would be between HLA-A * 24:02 and HLA-B * 27. While certain HLA-A and HLA-B variants can recognize the same epitopes (Marsh et al, 2021), it is not known if peptide kinetics could be the protective mechanism for these class I molecules. It is clear that HLA-A * 24:02, and amino acid residues 95 and 156, warrant further investigation as to their protective role in AS disease modification.…”

Evidence-Based Minireview: Strategies to manage a severely HLA-alloimmunized patient with refractory thrombocytopenia

“…When HLA anti gen-matched units are unavail able, epi topematched units and anti gen-neg a tive units are con sid ered equiva lently effi ca cious. 4,5 Epitope matching is based on the the ory that patients do not make antibodies against epi topes (poly mor phic amino acid config u ra tions shared among HLA anti gens) pres ent on non self HLA anti gens if they are also pres ent on self HLA anti gens. Computer algo rithms, like HLAMatchmaker, pre dict matching at the epitope level regard less of anti gen match sta tus (Figure 2D).…”