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

Department of Haematological Medicine, King's College Hospital, London, United Kingdom. Department of Haematology, School of Cancer and Pharmaceutical Sciences, Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom. Transfusion Medicine, NHS Blood and Transplant (NHSBT), Oxford, United Kingdom. Department of Haematology, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom. Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom. NIHR Oxford Biomedical Research Centre, Oxford, United Kingdom. NHSBT Clinical Trials Unit, Cambridge, United Kingdom. NHSBT Clinical Trials Unit, Bristol, United Kingdom. Haematology, Barts and The London Hospital, London, United Kingdom. H&I Laboratory, NHSBT, Colindale, United Kingdom. MRC Clinical Trials Unit, University College London, London, United Kingdom. Histocompatibility and Immunogenetics (H&I) Laboratory, NHSBT, Tooting, United Kingdom; and. Faculty of Life Sciences and Medicine, King's College London, University of London, London, United Kingdom.

Blood. 2021;137(3):310-322
PICO Summary

Population

Alloimmunized, platelet-refractory, thrombocytopenic patients with aplastic anemia, myelodysplastic syndrome, or acute myeloid leukemia (n= 49).

Intervention

HLA epitope-matched (HEM) platelet transfusions.

Comparison

HLA standard antigen-matched (HSM) platelet transfusions.

Outcome

For intention to treat, numbers of evaluable transfusions were 107 and 112 for HEM and HSM methods, respectively. Unadjusted mean platelet count increments (PCI) for HEM and HSM methods were 23.9 (standard deviation [SD], 15) and 23.5 (SD, 14.1), respectively. There were no differences in secondary outcomes of platelet counts, transfusion requirements, and bleeding events. Adequate 1-hour PCI was more frequently observed, with a mean number of 3.2 epitope mismatches, compared with 5.5 epitope mismatches for inadequate 1-hour increments.
Abstract
Platelet transfusion refractoriness results in adverse outcomes and increased health care costs. Managing refractoriness resulting from 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 randomized, double-blind, noninferiority, crossover trial comparing HLA epitope-matched (HEM) platelets with HLA standard antigen-matched (HSM) platelet transfusions. Alloimmunized, platelet-refractory, thrombocytopenic patients with aplastic anemia, myelodysplastic syndrome, or acute myeloid leukemia were eligible. HEM platelets were selected using HLAMatchMaker epitope (specifically eplet) matching. Patients received up to 8 prophylactic HEM and HSM transfusions provided in random order. The primary outcome was 1-hour posttransfusion platelet count increment (PCI). Forty-nine patients were randomized at 14 UK hospitals. For intention to treat, numbers of evaluable transfusions were 107 and 112 for HEM and HSM methods, respectively. Unadjusted mean PCIs for HEM and HSM methods were 23.9 (standard deviation [SD], 15) and 23.5 (SD, 14.1), respectively (adjusted mean difference, -0.1; 95% confidence interval [CI], -2.9 to 2.8). Because the lower limit of the 95% CI was not greater than the predefined noninferiority limit, the HEM approach was declared noninferior to the HSM approach. There were no differences in secondary outcomes of platelet counts, transfusion requirements, and bleeding events. Adequate 1-hour PCI was more frequently observed, with a mean number of 3.2 epitope mismatches, compared with 5.5 epitope mismatches for inadequate 1-hour increments. For every additional epitope mismatch, the likelihood of an adequate PCI decreased by 15%. Epitope-matched platelets should be considered to support HLA alloimmunized patients. This trial was registered at www.isrctn.com as #ISRCTN23996532.
Study details
Language : eng
Credits : Bibliographic data from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine