title: Conditioning with rabbit versus horse ATG dramatically alters clinical outcomes in identical twins with severe aplastic anemia transplanted with the same allogeneic donor.
abstract: Severe aplastic anemia (SAA) is a rare disorder leading to bone marrow failure, which if left untreated, is invariably fatal. Conventional therapies with immunosuppressive therapy or allogeneic hematopoietic stem cell transplantation (HSCT) are highly effective. HSCT can offer a greater outcome in younger patients who have an available HLA match-related donor. Recent studies showing the addition of antithymocyte globulin (ATG) to the conditioning regimen improves engraftment and reduces the risk of graft-versus-host disease (GVHD).There are currently two ATG preparations in the USA, equine (or horse) and rabbit ATG. These agents are pharmacologically distinct, having significant differences in their pharmacokinetics and in vivo immunosuppressive effects [N Engl J Med 365(5):430-438, 2011]. Here, we report a case of two monozygotic twins with constitutional SAA that evolved to myelodysplastic syndrome (MDS) who both underwent allogeneic peripheral blood stem cell transplantation (PBSC) from the same single HLA antigen mismatched sibling donor with the only difference in the transplant regimen being the type of ATG used in the preparative regimen; one twin received horse ATG and the other received rabbit ATG during conditioning. This report emphasizes that dramatic differences in donor T cell chimerism and clinical outcomes including GVHD can occur as a consequence of the type of ATG that is utilized in the transplant conditioning regimen. These differences highlight that these agents should not be considered interchangeable drugs when used in this setting.
authors.affiliation: Hematology Branch, National Heart Lung and Blood Institute (NHLBI), National Institute of Health (NIH), Bethesda, MD, USA. uyenphuong18@yahoo.com.
authors.forename: P T
authors.initials: PT
authors.lastname: Vo
authors.affiliation: Department of Hematology and Oncology, Georgia Regents University, Augusta, GA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Pantin
authors.affiliation: Hematology Branch, National Heart Lung and Blood Institute (NHLBI), National Institute of Health (NIH), Bethesda, MD, USA.
authors.forename: C
authors.initials: C
authors.lastname: Ramos
authors.affiliation: Hematology Branch, National Heart Lung and Blood Institute (NHLBI), National Institute of Health (NIH), Bethesda, MD, USA.
authors.forename: L
authors.initials: L
authors.lastname: Cook
authors.affiliation: Hematology Branch, National Heart Lung and Blood Institute (NHLBI), National Institute of Health (NIH), Bethesda, MD, USA.
authors.forename: E
authors.initials: E
authors.lastname: Cho
authors.affiliation: Department of Clinical Pathology, Hematology Services, National Heart Lung and Blood Institute (NHLBI), National Institute of Health (NIH), Bethesda, MD, USA.
authors.forename: R
authors.initials: R
authors.lastname: Kurlander
authors.affiliation: Cell Lab Processing Section, Department of Transfusion Medicine, National Institute of Health (NIH) Blood Bank, Bethesda, MD, USA.
authors.forename: H
authors.initials: H
authors.lastname: Khuu
authors.affiliation: Stem Cell Allogenic Transplantation, Hematology Branch, National Heart Lung and Blood Institute (NHLBI), National Institute of Health (NIH), Bethesda, MD, USA.
authors.forename: J
authors.initials: J
authors.lastname: Barrett
authors.affiliation: Department of Transfusion Medicine, National Heart Lung and Blood Institute (NHLBI), National Institute of Health (NIH), Bethesda, MD, USA.
authors.forename: S
authors.initials: S
authors.lastname: Leitman
authors.affiliation: Transplantation Immunotherapy, Hematology Branch, National Heart Lung and Blood Institute (NHLBI), National Institute of Health (NIH), Bethesda, MD, USA.
authors.forename: R W
authors.initials: RW
authors.lastname: Childs
mesh_terms: D000741:Anemia, Aplastic / Q000188:drug therapy*; D000818:Animals; D016026:Bone Marrow Transplantation / Q000379:methods*; D002648:Child; D018450:Disease Progression; D005260:Female; D006736:Horses; D006801:Humans; D011817:Rabbits; D035781:Siblings; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous / Q000379:methods*; D016896:Treatment Outcome; D014430:Twins, Monozygotic