An exploratory analysis of mitochondrial haplotypes and allogeneic hematopoietic cell transplantation outcomes

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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.

Original languageEnglish (US)
Pages (from-to)81-88
Number of pages8
JournalBiology of Blood and Marrow Transplantation
Volume21
Issue number1
DOIs
StatePublished - Jan 1 2015

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Cell Transplantation
Haplotypes
Tissue Donors
Confidence Intervals
Siblings
Graft vs Host Disease
Immunologic Monitoring
Validation Studies
Oxidative Phosphorylation
Recurrence
DNA

Keywords

  • Graft-versus-host disease
  • Hematopoietic cell transplantation
  • Mitochondria
  • Polymorphism

Cite this

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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.",
keywords = "Graft-versus-host disease, Hematopoietic cell transplantation, Mitochondria, Polymorphism",
author = "Ross, {Julie A.} and Jakub Tolar and Spector, {Logan G.} and Todd DeFor and Lund, {Troy C.} and Weisdorf, {Daniel J.} and Erica Langer and Hooten, {Anthony J.} and Bharat Thyagarajan and Gleason, {Michelle K.} and Wagner, {John E.} and Kimberly Robien and Verneris, {Michael R.}",
year = "2015",
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journal = "Biology of Blood and Marrow Transplantation",
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T1 - An exploratory analysis of mitochondrial haplotypes and allogeneic hematopoietic cell transplantation outcomes

AU - Ross, Julie A.

AU - Tolar, Jakub

AU - Spector, Logan G.

AU - DeFor, Todd

AU - Lund, Troy C.

AU - Weisdorf, Daniel J.

AU - Langer, Erica

AU - Hooten, Anthony J.

AU - Thyagarajan, Bharat

AU - Gleason, Michelle K.

AU - Wagner, John E.

AU - Robien, Kimberly

AU - Verneris, Michael R.

PY - 2015/1/1

Y1 - 2015/1/1

N2 - 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.

AB - 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.

KW - Graft-versus-host disease

KW - Hematopoietic cell transplantation

KW - Mitochondria

KW - Polymorphism

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