TY - JOUR
T1 - An epitope-based approach of HLA-matched platelets for transfusion
T2 - A noninferiority crossover randomized trial
AU - Marsh, Judith C.
AU - Stanworth, Simon J.
AU - Pankhurst, Laura A.
AU - Kallon, Delordson
AU - Gilbertson, Adeline Z.
AU - Pigden, Collette
AU - Deary, Alison J.
AU - Mora, Ana S.
AU - Brown, Joanne
AU - Laing, Emma S.
AU - Choo, Louise L.
AU - Hodge, Renate
AU - Llewelyn, Charlotte A.
AU - Harding, Kay
AU - Sage, Deborah
AU - Mijovic, Aleksandar
AU - Mufti, Ghulam J.
AU - Navarrete, Cristina V.
AU - Brown, Colin J.
N1 - Funding Information:
This report is independent research funded by NHS Blood and Transplant. The views expressed in this publication are those of the authors and not necessarily those of NHS Blood and Transplant.
Funding Information:
This work was supported by the NHS Blood and Transplant Research & Development Committee (BS08/3).
Publisher Copyright:
© 2021 by The American Society of Hematology. This trial was registered at www.isrctn.com as #ISRCTN23996532.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/1/21
Y1 - 2021/1/21
N2 - 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, 20.1; 95% confidence interval [CI], 22.9 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.
AB - 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, 20.1; 95% confidence interval [CI], 22.9 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.
UR - http://www.scopus.com/inward/record.url?scp=85099931943&partnerID=8YFLogxK
U2 - 10.1182/blood.2020007199
DO - 10.1182/blood.2020007199
M3 - Article
C2 - 33067624
AN - SCOPUS:85099931943
SN - 0006-4971
VL - 137
SP - 310
EP - 322
JO - Blood
JF - Blood
IS - 3
ER -