title: Long-term survival and late deaths after hematopoietic cell transplantation for primary immunodeficiency diseases and inborn errors of metabolism.
abstract: It is uncertain whether late mortality rates after hematopoietic cell transplantation for severe combined immunodeficiency (SCID), non-SCID primary immunodeficiency diseases (non-SCID PIDD), and inborn errors of metabolism (IEM) return to rates observed in the general population, matched for age, sex, and nationality. We studied patients with SCID (n = 201), non-SCID PIDD (n = 405), and IEM (n = 348) who survived for at least 2 years after transplantation with normal T cell function (SCID) or >95% donor chimerism (non-SCID PIDD and IEM). Importantly, mortality rate was significantly higher in these patients compared with the general population for several years after transplantation. The rate decreased toward the normal rate in patients with SCID and non-SCID PIDD beyond 6 years after transplantation, but not in patients with IEM. Active chronic graft-versus-host disease at 2 years was associated with increased risk of late mortality for all diseases (hazard ratio [HR], 1.87; P = .05). In addition, late mortality was higher in patients with non-SCID PIDD who received T cell-depleted grafts (HR 4.16; P = .007) and in patients with IEM who received unrelated donor grafts (HR, 2.72; P = .03) or mismatched related donor grafts (HR, 3.76; P = .01). The finding of higher mortality rates in these long-term survivors for many years after transplantation confirms the need for long-term surveillance.
authors.affiliation: Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee 53226, USA. meapen@mcw.edu
authors.forename: Mary
authors.initials: M
authors.lastname: Eapen
authors.forename: Kwang Woo
authors.initials: KW
authors.lastname: Ahn
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Orchard
authors.forename: Morton J
authors.initials: MJ
authors.lastname: Cowan
authors.forename: Stella M
authors.initials: SM
authors.lastname: Davies
authors.forename: Anders
authors.initials: A
authors.lastname: Fasth
authors.forename: Anna
authors.initials: A
authors.lastname: Hassebroek
authors.forename: Mouhab
authors.initials: M
authors.lastname: Ayas
authors.forename: Carmem
authors.initials: C
authors.lastname: Bonfim
authors.forename: Tracey A
authors.initials: TA
authors.lastname: O'Brien
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Gross
authors.forename: Mitchell
authors.initials: M
authors.lastname: Horwitz
authors.forename: Edwin
authors.initials: E
authors.lastname: Horwitz
authors.forename: Neena
authors.initials: N
authors.lastname: Kapoor
authors.forename: Joanne
authors.initials: J
authors.lastname: Kurtzberg
authors.forename: Navneet
authors.initials: N
authors.lastname: Majhail
authors.forename: Olle
authors.initials: O
authors.lastname: Ringden
authors.forename: Paul
authors.initials: P
authors.lastname: Szabolcs
authors.forename: Paul
authors.initials: P
authors.lastname: Veys
authors.forename: K Scott
authors.initials: KS
authors.lastname: Baker
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D005060:Europe; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000276:immunology / Q000401:mortality* / Q000628:therapy; D007223:Infant; D007391:International Cooperation; D008297:Male; D008661:Metabolism, Inborn Errors / Q000276:immunology / Q000401:mortality* / Q000628:therapy; D016511:Severe Combined Immunodeficiency / Q000276:immunology / Q000401:mortality* / Q000628:therapy; D016019:Survival Analysis; D013997:Time Factors; D018183:Transplantation Chimera; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D014481:United States; D061349:Unrelated Donors