title: An exploratory analysis of mitochondrial haplotypes and allogeneic hematopoietic cell transplantation outcomes.
abstract: Certain mitochondrial haplotypes (mthaps) are associated with disease, possibly through differences in oxidative phosphorylation and/or immunosurveillance. We explored whether mthaps are associated with allogeneic hematopoietic cell transplantation (HCT) outcomes. Recipient (n = 437) and donor (n = 327) DNA were genotyped for common European mthaps (H, J, U, T, Z, K, V, X, I, W, and K2). HCT outcomes for mthap matched siblings (n = 198), all recipients, and all donors were modeled using relative risks (RR) and 95% confidence intervals and compared with mthap H, the most common mitochondrial haplotypes. Siblings with I and V were significantly more likely to die within 5 years (RR = 3.0; 95% confidence interval [CI], 1.2 to 7.9; and RR = 4.6; 95% CI, 1.8 to 12.3, respectively). W siblings experienced higher acute graft-versus-host disease (GVHD) grades II to IV events (RR = 2.1; 95% CI, 1.1 to 2.4) with no events for those with K or K2. Similar results were observed for all recipients combined, although J recipients experienced lower GVHD and higher relapse. Patients with I donors had a 2.7-fold (1.2 to 6.2) increased risk of death in 5 years, whereas few patients with K2 or W donors died. No patients with K2 donors and few patients with U donors relapsed. Mthap may be an important consideration in HCT outcomes, although validation and functional studies are needed. If confirmed, it may be feasible to select donors based on mthap to increase positive or decrease negative outcomes.
authors.affiliation: Division of Epidemiology and Clinical Research, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota; Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota. Electronic address: rossx014@umn.edu.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Ross
authors.affiliation: Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota; Stem Cell Institute, University of Minnesota, Minneapolis, Minnesota; Division of Blood and Marrow Transplantation, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Jakub
authors.initials: J
authors.lastname: Tolar
authors.affiliation: Division of Epidemiology and Clinical Research, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota; Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Logan G
authors.initials: LG
authors.lastname: Spector
authors.affiliation: Division of Blood and Marrow Transplantation, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Todd
authors.initials: T
authors.lastname: DeFor
authors.affiliation: Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota; Division of Blood and Marrow Transplantation, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Troy C
authors.initials: TC
authors.lastname: Lund
authors.affiliation: Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota; Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Weisdorf
authors.affiliation: Division of Epidemiology and Clinical Research, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota; Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Erica
authors.initials: E
authors.lastname: Langer
authors.affiliation: Division of Epidemiology and Clinical Research, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota; Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Hooten
authors.affiliation: Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota; Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Bharat
authors.initials: B
authors.lastname: Thyagarajan
authors.affiliation: Division of Epidemiology and Clinical Research, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota; Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Michelle K
authors.initials: MK
authors.lastname: Gleason
authors.affiliation: Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota; Division of Blood and Marrow Transplantation, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota.
authors.forename: John E
authors.initials: JE
authors.lastname: Wagner
authors.affiliation: School of Public Health, George Washington University, Washington, DC.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Robien
authors.affiliation: Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota; Division of Blood and Marrow Transplantation, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Verneris
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D006086:Graft vs Host Disease / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D006239:Haplotypes; D019337:Hematologic Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D008875:Middle Aged; D008928:Mitochondria / Q000235:genetics* / Q000276:immunology; D011379:Prognosis; D035781:Siblings; D016019:Survival Analysis; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D061349:Unrelated Donors
keywords: Graft-versus-host disease; Hematopoietic cell transplantation; Mitochondria; Polymorphism