title: Nonmyeloablative peripheral blood haploidentical stem cell transplantation for refractory severe aplastic anemia.
abstract: New transplant approaches are urgently needed for patients with refractory severe aplastic anemia (SAA) who lack a matched sibling or unrelated donor (UD) or who have failed UD or cord blood transplant. Patients with refractory SAA are at risk of later clonal evolution to myelodysplastic syndrome and acute leukemia. We report our pilot findings with haploidentical hematopoietic stem cell transplantation (haploHSCT) using uniform reduced-intensity conditioning with postgraft high-dose cyclophosphamide in 8 patients with refractory SAA or patients who rejected a prior UD or cord blood transplant. Six of 8 patients engrafted. Graft failure was associated with donor-directed HLA antibodies, despite intensive pre-HSCT desensitization with plasma exchange and rituximab. There was only 1 case of grade II skin graft-versus-host disease. We show that haploHSCT can successfully rescue refractory SAA patients who lack donor-directed HLA antibodies but not in the presence of donor-directed HLA antibodies. This novel protocol for haploHSCT for SAA has been adopted by the European Group for Blood and Marrow Transplantation Severe Aplastic Anaemia Working Party for a future noninterventional, observational study to further evaluate its efficacy.
authors.affiliation: Department of Hematological Medicine, King's College Hospital, London, United Kingdom.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Clay
authors.affiliation: Department of Hematological Medicine, King's College Hospital, London, United Kingdom.
authors.forename: Austin G
authors.initials: AG
authors.lastname: Kulasekararaj
authors.affiliation: Department of Hematological Medicine, King's College Hospital, London, United Kingdom.
authors.forename: Victoria
authors.initials: V
authors.lastname: Potter
authors.affiliation: Department of Hematological Medicine, King's College Hospital, London, United Kingdom.
authors.forename: Francesco
authors.initials: F
authors.lastname: Grimaldi
authors.affiliation: Department of Hematological Medicine, King's College Hospital, London, United Kingdom.
authors.forename: Donal
authors.initials: D
authors.lastname: McLornan
authors.affiliation: Department of Hematological Medicine, King's College Hospital, London, United Kingdom.
authors.forename: Kavita
authors.initials: K
authors.lastname: Raj
authors.affiliation: Department of Hematological Medicine, King's College Hospital, London, United Kingdom.
authors.forename: Hugues
authors.initials: H
authors.lastname: de Lavallade
authors.affiliation: Department of Hematological Medicine, King's College Hospital, London, United Kingdom.
authors.forename: Michelle
authors.initials: M
authors.lastname: Kenyon
authors.affiliation: Department of Hematological Medicine, King's College Hospital, London, United Kingdom.
authors.forename: Antonio
authors.initials: A
authors.lastname: Pagliuca
authors.affiliation: Department of Hematological Medicine, King's College Hospital, London, United Kingdom; Department of Haematological Medicine, King's College London, London, United Kingdom.
authors.forename: Ghulam J
authors.initials: GJ
authors.lastname: Mufti
authors.affiliation: Department of Hematological Medicine, King's College Hospital, London, United Kingdom; Department of Haematological Medicine, King's College London, London, United Kingdom. Electronic address: Judith.marsh@nhs.net.
authors.forename: Judith C W
authors.initials: JC
authors.lastname: Marsh
mesh_terms: D000328:Adult; D000741:Anemia, Aplastic / Q000628:therapy*; D000753:Anemia, Refractory / Q000628:therapy*; D015331:Cohort Studies; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D014019:Tissue Donors; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D055815:Young Adult
keywords: Aplastic anemia; HSCT; Haploidentical; Nonmyeloablative; Stem cell transplant