Risk of HLA antibody generation after receipt of Mirasol versus standard platelets in the MIPLATE randomized trial.
alloimmunization
pathogen reduction
platelets
Journal
Transfusion
ISSN: 1537-2995
Titre abrégé: Transfusion
Pays: United States
ID NLM: 0417360
Informations de publication
Date de publication:
04 2023
04 2023
Historique:
revised:
06
01
2023
received:
18
10
2022
accepted:
30
01
2023
medline:
12
4
2023
pubmed:
26
2
2023
entrez:
25
2
2023
Statut:
ppublish
Résumé
Human leukocyte antigen (HLA) alloimmunization can occur after platelet transfusion. These antibodies can complicate future platelet transfusions or organ transplantation. Animal data suggest that Mirasol pathogen reduction treatment (PRT) can prevent alloimmunization after transfusion. The MIPLATE trial enrolled 330 of a planned 660 participants with hematological malignancies at risk for grade 2 or greater bleeding. The study was halted early for futility after a planned interim analysis. Participants were randomized to receive PRT versus standard control platelets. Serum samples were collected from participants at baseline (pretransfusion), weekly for the first 4 weeks, then at days 42 and 56. HLA antibody levels were determined using a commercial multianalyte bead-based assay. HLA antibody levels were analyzed using low, medium, and high cutoffs based on prior studies. The rate of alloimmunization was low in both arms of the study, particularly at the high HLA antibody cutoff (total of 6 of 277 subjects at risk, or 2.2%). The risk of alloimmunization did not differ between study arms, nor did the risk of immune refractoriness to platelet transfusion. The data do not support the conclusion that Mirasol exerted a protective effect against alloimmunization after platelet transfusion in the MIPLATE trial.
Sections du résumé
BACKGROUND
Human leukocyte antigen (HLA) alloimmunization can occur after platelet transfusion. These antibodies can complicate future platelet transfusions or organ transplantation. Animal data suggest that Mirasol pathogen reduction treatment (PRT) can prevent alloimmunization after transfusion.
STUDY DESIGN AND METHODS
The MIPLATE trial enrolled 330 of a planned 660 participants with hematological malignancies at risk for grade 2 or greater bleeding. The study was halted early for futility after a planned interim analysis. Participants were randomized to receive PRT versus standard control platelets. Serum samples were collected from participants at baseline (pretransfusion), weekly for the first 4 weeks, then at days 42 and 56. HLA antibody levels were determined using a commercial multianalyte bead-based assay. HLA antibody levels were analyzed using low, medium, and high cutoffs based on prior studies.
RESULTS
The rate of alloimmunization was low in both arms of the study, particularly at the high HLA antibody cutoff (total of 6 of 277 subjects at risk, or 2.2%). The risk of alloimmunization did not differ between study arms, nor did the risk of immune refractoriness to platelet transfusion.
CONCLUSIONS
The data do not support the conclusion that Mirasol exerted a protective effect against alloimmunization after platelet transfusion in the MIPLATE trial.
Substances chimiques
Isoantibodies
0
HLA Antigens
0
Histocompatibility Antigens Class I
0
Types de publication
Randomized Controlled Trial
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
791-797Informations de copyright
© 2023 AABB.
Références
Stanworth SJ, Navarrete C, Estcourt L, Marsh J. Platelet refractoriness - practical approaches and ongoing dilemmas in patient management. Br J Haematol. 2015;171(3):297-305.
Freedman J, Gafni A, Garvey MB, Blanchette V. A cost-effectiveness evaluation of platelet crossmatching and HLA matching in the management of alloimmunized thrombocytopenic patients. Transfusion. 1989;29(3):201-7.
Leukocyte reduction and ultraviolet B irradiation of platelets to prevent alloimmunization and refractoriness to platelet transfusions. The trial to reduce alloimmunization to platelets study group. N Engl J Med. 1997;337:1861-9.
Williamson LM, Wimperis JZ, Williamson P, Copplestone JA, Gooi HC, Morgenstern GR, et al. Bedside filtration of blood products in the prevention of HLA alloimmunization--a prospective randomized study. Alloimmunisation Study Group. Blood. 1994;83:3028-35.
Sniecinski I, O'Donnell MR, Nowicki B, Hill LR. Prevention of refractoriness and HLA-alloimmunization using filtered blood products. Blood. 1988;71:1402-7.
Slichter SJ, Pellham E, Bailey SL, Christoffel T, Gettinger I, Gaur L, et al. Leukofiltration plus pathogen reduction prevents alloimmune platelet refractoriness in a dog transfusion model. Blood. 2017;130(8):1052-61.
Slichter SJ, Bailey SL, Gettinger I, Pellham E, Christoffel T, Castro G, et al. Pathogen reduction with amotosalen/UVA reduces platelet refractoriness in a dog platelet transfusion model. Vox Sang. 2019;114(6):595-604.
Jackman RP, Heitman JW, Marschner S, Goodrich RP, Norris PJ. Understanding loss of donor white blood cell immunogenicity after pathogen reduction: mechanisms of action in ultraviolet illumination and riboflavin treatment. Transfusion. 2009;49:2686-99.
Jackman RP, Muench MO, Heitman JW, Inglis HC, Law JP, Marschner S, et al. Immune modulation and lack of alloimmunization following transfusion with pathogen-reduced platelets in mice. Transfusion. 2013;53(11):2697-709.
Jackman RP, Deng X, Bolgiano D, Utter GH, Schechterly C, Lebedeva M, et al. Leukoreduction and ultraviolet treatment reduce both the magnitude and the duration of the HLA antibody response. Transfusion. 2014;54(3):672-80.
Norris PJ, Kaidarova Z, Maiorana E, Milani S, Lebedeva M, Busch MP, et al. Ultraviolet light-based pathogen inactivation and alloimmunization after platelet transfusion: results from a randomized trial. Transfusion. 2018;58(5):1210-7.
Saris A, Kerkhoffs JL, Norris PJ, Ham SM, Brinke A, Brand A, et al. The role of pathogen-reduced platelet transfusions on HLA alloimmunization in hemato-oncological patients. Transfusion. 2019;59(2):470-81.
van der Meer PF, Ypma PF, van Geloven N, van Hilten JA, van Wordragen-Vlaswinkel RJ, Eissen O, et al. Hemostatic efficacy of pathogen-inactivated vs untreated platelets: a randomized controlled trial. Blood. 2018;132(2):223-31.
Carrick DM, Norris PJ, Endres RO, Pandey S, Kleinman SH, Wright D, et al. Establishing assay cutoffs for HLA antibody screening of apheresis donors. Transfusion. 2011;51:2092-101.
Jackman RP, Deng X, Bolgiano D, Lebedeva M, Heitman JW, Busch MP, et al. Low-level HLA antibodies do not predict platelet transfusion failure in TRAP study participants. Blood. 2013;121(16):3261-6.
Jackman RP, Utter GH, Lee T-H, Montalvo L, Wen L, Chafets D, et al. Lack of persistent microchimerism in contemporary transfused trauma patients. Transfusion. 2019;59(11):3329-36.