title: Effects of mobilization regimens in donors on outcomes of hematopoietic cell transplantation in miniature Swine.
abstract: Toxicities and complications associated with hematopoietic cell transplantation currently limit this potentially curative therapy for malignant and nonmalignant blood disorders. Miniature swine provide a clinically relevant model for studies to improve posttransplantation outcomes. Miniature swine recipients of high-dose haploidentical hepatopoietic cell transplantation after reduced-intensity conditioning consisting of low-dose (100 cGy) total-body irradiation, partial T-cell depletion by using a CD3 immunotoxin, and a 45-d course of cyclosporine A typically successfully engraft without graft-versus-host disease. We recently observed broad variability in engraftment outcomes that correlates with the occurrence of adverse reactions in donors after cytokine treatment to mobilize hematopoietic progenitor cells from the bone marrow to the peripheral blood for collection. Haploidentical recipients (n = 16) of cells from donors remaining healthy during cytokine treatment engrafted with multilineage chimerism, did not develop graft-versus-host disease, and did not require any blood products. In comparison, identically conditioned recipients of cells from donors that had severe reactions during cytokine treatment had adverse outcomes, including the development of clinically significant thrombocytopenia requiring blood product support in 8 of 11 swine. Furthermore, all 11 recipients lost peripheral blood myeloid chimerism (indicating lack of engraftment of donor stem cells). These data suggest that posttransplantation complications in swine are influenced by the health status of the donor before and during the collection of hematopoietic cells by leukapheresis.
authors.affiliation: Transplantation Biology Research Center, and Transplant Center, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Abraham J
authors.initials: AJ
authors.lastname: Matar
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Crepeau
authors.forename: Vimukthi
authors.initials: V
authors.lastname: Pathiraja
authors.forename: Simon
authors.initials: S
authors.lastname: Robson
authors.forename: Jay A
authors.initials: JA
authors.lastname: Fishman
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Spitzer
authors.forename: David H
authors.initials: DH
authors.lastname: Sachs
authors.forename: Christene A
authors.initials: CA
authors.lastname: Huang
authors.forename: Raimon
authors.initials: R
authors.lastname: Duran-Struuck
mesh_terms: D000818:Animals; D016572:Cyclosporine / Q000627:therapeutic use; D016207:Cytokines / Q000494:pharmacology; D017931:DNA Primers / Q000235:genetics; D006085:Graft Survival / Q000502:physiology*; D006402:Hematologic Diseases / Q000628:therapy*; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D000922:Immunotoxins / Q000627:therapeutic use; D007937:Leukapheresis / Q000379:methods; D016133:Polymerase Chain Reaction; D013552:Swine; D013556:Swine, Miniature; D019172:Transplantation Conditioning / Q000379:methods*; D016896:Treatment Outcome; D014916:Whole-Body Irradiation
chemical_list: D016207:Cytokines; D017931:DNA Primers; D000922:Immunotoxins; D016572:Cyclosporine
references.citation: Transplantation. 1999 Sep 27;68(6):855-60
references.pmid: 10515387
references.citation: Br J Haematol. 2006 Dec;135(5):642-50
references.pmid: 17054431
references.citation: Transplant Proc. 2009 Mar;41(2):539-41
references.pmid: 19328921
references.citation: N Engl J Med. 1999 Aug 19;341(8):586-92
references.pmid: 10451465
references.citation: Clin J Am Soc Nephrol. 2011 May;6(5):1160-7
references.pmid: 21372214
references.citation: Blood. 2009 Apr 9;113(15):3604-11
references.pmid: 19190248
references.citation: Vet Immunol Immunopathol. 2010 Jun 15;135(3-4):243-56
references.pmid: 20079939
references.citation: Transplantation. 1976 Dec;22(6):559-67
references.pmid: 137560
references.citation: Lancet. 2009 May 2;373(9674):1550-61
references.pmid: 19282026
references.citation: N Engl J Med. 2006 Apr 27;354(17):1813-26
references.pmid: 16641398
references.citation: Blood. 2009 Jan 8;113(2):273-8
references.pmid: 18832652
references.citation: Transplantation. 2006 Jun 27;81(12):1677-85
references.pmid: 16794534
references.citation: Transplant Proc. 1993 Feb;25(1 Pt 2):1234-6
references.pmid: 8442099
references.citation: Biol Blood Marrow Transplant. 1999;5(6):347-56
references.pmid: 10595812
references.citation: J Vet Pharmacol Ther. 2012 Aug;35(4):382-8
references.pmid: 21736588
references.citation: Blood. 1990 Feb 15;75(4):1011-6
references.pmid: 2405918
references.citation: Xenotransplantation. 1999 Feb;6(1):17-27
references.pmid: 10355729
references.citation: Bioconjug Chem. 2011 Oct 19;22(10):2014-20
references.pmid: 21866954
references.citation: Blood Coagul Fibrinolysis. 2009 Jan;20(1):41-6
references.pmid: 19129727
references.citation: Haematologica. 2009 Jan;94(1):94-101
references.pmid: 19059940
references.citation: Tissue Antigens. 1999 Jul;54(1):43-52
references.pmid: 10458322
references.citation: Blood. 2008 Feb 15;111(4):1767-72
references.pmid: 18057230
references.citation: Biol Blood Marrow Transplant. 2003 Sep;9(9):571-82
references.pmid: 14506659