title: Persistence of recipient human leucocyte antigen (HLA) antibodies and production of donor HLA antibodies following reduced intensity allogeneic haematopoietic stem cell transplantation.
abstract: The effects of reduced intensity conditioning (RIC) on human leucocyte antigen (HLA)-alloimmunization and platelet transfusion refractoriness (PTR) following allogeneic haematopoietic stem cell transplantation (Allo-HSCT) are unknown. We studied HLA-alloantibodies in a cohort of 16 patients (eight HLA-alloimmunized with pre-transplant histories of PTR and eight non-alloimmunized controls) undergoing Allo-HSCT using fludarabine/cyclophosphamide-based RIC. Pre- and post-transplant serum samples were analysed for HLA-antibodies and compared to myeloid, T-cell and bone marrow plasma cell chimaerism. Among alloimmunized patients, the duration that HLA-antibodies persisted post-transplant correlated strongly with pre-transplant HLA-antibody mean fluorescence intensity (MFI) and PRA levels (Spearman's rank correlation = 0·954 (P = 0·0048) and 0·865 (P = 0·0083) respectively). Pre-transplant MFI >10,000 was associated with post-transplant HLA antibody persistence >100 d (P = 0·029). HLA-antibodies persisted ≥100 d in 3/8 patients despite recipient chimaerism being undetectable in all lympho-haematopoietic lineages including plasma cells. Post-transplant de-novo HLA-antibodies developed in three control patients with two developing PTR; the donors for two of these patients demonstrated pre-existing HLA-antibodies of equivalent specificity to those in the patient, confirming donor origin. These data show HLA-antibodies may persist for prolonged periods following RIC. Further study is needed to determine the incidence of post-transplant PTR as a consequence of donor-derived HLA alloimmunization before recommendations on donor HLA-antibody screening can be made.
authors.affiliation: Division of Haematology/Oncology, Children's National Medical Centre, Washington, DC, USA.
authors.forename: Ross M
authors.initials: RM
authors.lastname: Fasano
authors.forename: Ewelina
authors.initials: E
authors.lastname: Mamcarz
authors.forename: Sharon
authors.initials: S
authors.lastname: Adams
authors.forename: Theresa
authors.initials: T
authors.lastname: Donohue Jerussi
authors.forename: Kyoko
authors.initials: K
authors.lastname: Sugimoto
authors.forename: Xin
authors.initials: X
authors.lastname: Tian
authors.forename: Willy A
authors.initials: WA
authors.lastname: Flegel
authors.forename: Richard W
authors.initials: RW
authors.lastname: Childs
mesh_terms: D000293:Adolescent; D000328:Adult; D000918:Antibody Specificity / Q000276:immunology; D002648:Child; D005260:Female; D006085:Graft Survival; D006680:HLA Antigens / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007518:Isoantibodies / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D019172:Transplantation Conditioning; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D006680:HLA Antigens; D007518:Isoantibodies
keywords: HLA antibodies; allogeneic bone marrow transplantation; platelets
references.citation: Hum Immunol. 2011 May;72(5):386-91
references.pmid: 21320562
references.citation: Leukemia. 2001 Dec;15(12):1885-91
references.pmid: 11753609
references.citation: Transplantation. 2009 Oct 27;88(8):1019-24
references.pmid: 19855248
references.citation: Blood. 1999 Nov 1;94(9):3234-41
references.pmid: 10556212
references.citation: Transfusion. 2009 Sep;49(9):1825-35
references.pmid: 19453983
references.citation: Transfusion. 2008 Apr;48(4):791-3
references.pmid: 18366463
references.citation: Bone Marrow Transplant. 2012 Dec;47(12):1499-506
references.pmid: 22231464
references.citation: Curr Opin Immunol. 2009 Oct;21(5):569-72
references.pmid: 19682882
references.citation: Bone Marrow Transplant. 2012 Oct;47(10):1338-42
references.pmid: 22367345
references.citation: Transplantation. 2009 Feb 15;87(3):415-8
references.pmid: 19202448
references.citation: Am J Transplant. 2008 Jan;8(1):133-43
references.pmid: 18184311
references.citation: Transfusion. 1990 Sep;30(7):622-5
references.pmid: 2402776
references.citation: Transfusion. 2007 Feb;47(2):326-34
references.pmid: 17302780
references.citation: Blood. 2011 Dec 15;118(25):6691-7
references.pmid: 21940825
references.citation: Blood. 2010 Oct 14;116(15):2839-46
references.pmid: 20628152
references.citation: J Lab Clin Med. 1988 Nov;112(5):634-40
references.pmid: 3183495
references.citation: Blood. 2002 Aug 15;100(4):1484-9
references.pmid: 12149235
references.citation: Biol Blood Marrow Transplant. 2001;7(9):473-85
references.pmid: 11669214
references.citation: Bone Marrow Transplant. 1996 Jun;17(6):1035-41
references.pmid: 8807111
references.citation: Br J Haematol. 2005 Mar;128(5):668-75
references.pmid: 15725089
references.citation: Transpl Immunol. 2004 Jun-Jul;13(1):63-71
references.pmid: 15203130
references.citation: Blood. 2006 Feb 15;107(4):1680-7
references.pmid: 16269623
references.citation: N Engl J Med. 1997 Dec 25;337(26):1861-9
references.pmid: 9417523
references.citation: Immunol Res. 2010 Jul;47(1-3):257-64
references.pmid: 20087679
references.citation: Blood. 2011 Nov 24;118(22):5957-64
references.pmid: 21967975
references.citation: Nat Rev Nephrol. 2010 May;6(5):297-306
references.pmid: 20234355
references.citation: Blood. 2010 Apr 1;115(13):2704-8
references.pmid: 20089963
references.citation: Pediatr Transplant. 2011 Dec;15(8):E177-82
references.pmid: 20880381
references.citation: Transplantation. 1991 Feb;51(2):324-9
references.pmid: 1994523
references.citation: Tissue Antigens. 2011 Jan;77(1):3-8
references.pmid: 21155718
references.citation: Transfusion. 1999 Jan;39(1):103-6
references.pmid: 9920173
references.citation: Tissue Antigens. 2008 Aug;72(2):98-104
references.pmid: 18721269