HLA-C Antigen Mismatch Is Associated with Worse Outcome in Unrelated Donor Peripheral Blood Stem Cell Transplantation

Ann Woolfrey; John P. Klein; Michael Haagenson; Stephen Spellman; Effie Petersdorf; Machteld Oudshoorn; James Gajewski; Gregory A. Hale; John Horan; Minoo Battiwalla; Susana R. Marino; Michelle Setterholm; Olle Ringden; Carolyn Hurley; Neal Flomenberg; Claudio Anasetti; Marcelo Fernandez-Vina; Stephanie J. Lee

doi:10.1016/j.bbmt.2010.09.012

HLA-C Antigen Mismatch Is Associated with Worse Outcome in Unrelated Donor Peripheral Blood Stem Cell Transplantation

Ann Woolfrey
, John P. Klein
, Michael Haagenson
, Stephen Spellman
, Effie Petersdorf
, Machteld Oudshoorn
, James Gajewski
, Gregory A. Hale
, John Horan
, Minoo Battiwalla
, Susana R. Marino
, Michelle Setterholm
, Olle Ringden
, Carolyn Hurley
, Neal Flomenberg
, Claudio Anasetti
, Marcelo Fernandez-Vina
, Stephanie J. Lee

Hematology & Medical Oncology

Research output: Contribution to journal › Article › peer-review

195 Scopus citations

Abstract

The association between HLA matching and outcome in unrelated-donor peripheral blood stem cell (PBSC) transplantation has not yet been established. In the present study, a total of 1933 unrelated donor-recipient pairs who underwent PBSC transplantation between 1999 and 2006 for acute myelogenous leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, or chronic myelogenous leukemia and received high-resolution HLA typing for HLA-A, -B, -C, -DRB1, -DQA1, and -DQB1 were included in the analysis. Outcomes were compared between HLA-matched and HLA-mismatched pairs, adjusting for patient and transplant characteristics. Matching for HLA-A, -B, -C, and -DRB1 alleles (8/8 match) was associated with better survival at 1 year compared with 7/8 HLA-matched pairs (56% vs 47%). Using 8/8 HLA-matched patients as the baseline (n = 1243), HLA-C antigen mismatches (n = 189) were statistically significantly associated with lower leukemia-free survival (relative risk [RR], 1.36; 95% confidence interval [CI], 1.13-1.64; P = .0010), and increased risk for mortality (RR, 1.41; 95% CI, 1.16-1.70; P = .0005), treatment-related mortality (RR, 1.61; 95% CI, 1.25-2.08; P = .0002), and grade III-IV graft-versus-host disease (RR, 1.98; 95% CI, 1.50-2.62; P < .0001). HLA-B antigen or allele mismatching was associated with an increased risk for acute GVHD grade III-IV. No statistically significant differences in outcome were observed for HLA-C allele (n = 61), HLA-A antigen/allele (n = 136), HLA-DRB1 allele (n = 39), or HLA-DQ antigen/allele (n = 114) mismatches compared with 8/8 HLA-matched pairs. HLA mismatch was not associated with relapse or chronic GVHD. HLA-C antigen-mismatched unrelated PBSC donors were associated with worse outcomes compared with 8/8 HLA-matched donors. The study's limited power due to small sample size precludes conclusions about other mismatches.

Original language	English (US)
Pages (from-to)	885-892
Number of pages	8
Journal	Biology of Blood and Marrow Transplantation
Volume	17
Issue number	6
DOIs	https://doi.org/10.1016/j.bbmt.2010.09.012
State	Published - Jun 1 2011

Funding

Financial disclosure: The CIBMTR is supported by Public Health Service Grant/Cooperative Agreement U24-CA76518 from the National Cancer Institute (NCI) , the National Heart, Lung and Blood Institute (NHLBI) , and the National Institute of Allergy and Infectious Diseases ; NHLBI-NCI Grant/Cooperative Agreement 5U01HL069294 ; Health Resources and Services Administration Contract HHSH234200637015C ; Office of Naval Research Grants N00014-06-1-0704 and N00014-08-1-0058 ; and grants from AABB, Aetna, American Society for Blood and Marrow Transplantation, Amgen Inc, anonymous donation to the Medical College of Wisconsin, Astellas Pharma US Inc, Baxter International Inc, Bayer HealthCare Pharmaceuticals, Be the Match Foundation, Biogen IDEC, BioMarin Pharmaceutical Inc, Biovitrum AB, BloodCenter of Wisconsin, Blue Cross and Blue Shield Association, Bone Marrow Foundation, Canadian Blood and Marrow Transplant Group, CaridianBCT, Celgene Corporation, CellGenix GmbH, Centers for Disease Control and Prevention, Children’s Leukemia Research Association, ClinImmune Labs, CTI Clinical Trial and Consulting Services, Cubist Pharmaceuticals, Cylex Inc, CytoTherm, DOR BioPharma Inc, Dynal Biotech (an Invitrogen company), Eisai Inc, Enzon Pharmaceuticals Inc, European Group for Blood and Marrow Transplantation, Gamida Cell Ltd, GE Healthcare, Genentech Inc, Genzyme Corporation, Histogenetics Inc, HKS Medical Information Systems, Hospira Inc, Infectious Diseases Society of America, Kiadis Pharma, Kirin Brewery Co Ltd, Leukemia & Lymphoma Society, Merck & Company, Medical College of Wisconsin, MGI Pharma Inc, Michigan Community Blood Centers, Millennium Pharmaceuticals Inc, Miller Pharmacal Group, Milliman USA Inc, Miltenyi Biotec Inc, National Marrow Donor Program, Nature Publishing Group, New York Blood Center, Novartis Oncology, Oncology Nursing Society, Osiris Therapeutics Inc, Otsuka America Pharmaceutical Inc, Pall Life Sciences, Pfizer Inc, Saladax Biomedical Inc, Schering Corporation, Society for Healthcare Epidemiology of America, Soligenix Inc, StemCyte Inc, StemSoft Software Inc, Sysmex America Inc, THERAKOS Inc, Thermogenesis Corporation, Vidacare Corporation, Vion Pharmaceuticals Inc, ViraCor Laboratories, ViroPharma Inc, and Wellpoint Inc . The views expressed in this article do not reflect the official policy or position of the National Institutes of Health, Department of the Navy, Department of Defense, or any other agency of the US Government.

Funders	Funder number
Amgen Inc.
Cubist Pharmaceuticals
Cylex Inc.
Hospira, Inc.
MGI Pharma, Inc.
Nature Publishing Group, New York Blood Center
Schering Corporation, Society for Healthcare Epidemiology of America
Soligenix, Inc.
Office of Naval Research	N00014-06-1-0704, N00014-08-1-0058
National Institute of Health National Heart, Lung, and Blood Institute
National Institute of Health-National Cancer Institute	U24CA076518
National Institute of Allergy and Infectious Diseases	5U01HL069294
Health Resources and Services Administration	HHSH234200637015C
Enzon Pharmaceuticals
American Society for Blood and Marrow Transplantation
Arrow Bone Marrow Transplant Foundation
Bayer Healthcare
Eisai

Keywords

Disease free survival
Graft-vs-Host disease
HLA Mismatch
HLA-C antigen
Hematopoietic cell transplantation

ASJC Scopus subject areas

Hematology
Transplantation

Access to Document

10.1016/j.bbmt.2010.09.012

Cite this

Woolfrey, A., Klein, J. P., Haagenson, M., Spellman, S., Petersdorf, E., Oudshoorn, M., Gajewski, J., Hale, G. A., Horan, J., Battiwalla, M., Marino, S. R., Setterholm, M., Ringden, O., Hurley, C., Flomenberg, N., Anasetti, C., Fernandez-Vina, M., & Lee, S. J. (2011). HLA-C Antigen Mismatch Is Associated with Worse Outcome in Unrelated Donor Peripheral Blood Stem Cell Transplantation. Biology of Blood and Marrow Transplantation, 17(6), 885-892. https://doi.org/10.1016/j.bbmt.2010.09.012

Woolfrey, A, Klein, JP, Haagenson, M, Spellman, S, Petersdorf, E, Oudshoorn, M, Gajewski, J, Hale, GA, Horan, J, Battiwalla, M, Marino, SR, Setterholm, M, Ringden, O, Hurley, C, Flomenberg, N, Anasetti, C, Fernandez-Vina, M & Lee, SJ 2011, 'HLA-C Antigen Mismatch Is Associated with Worse Outcome in Unrelated Donor Peripheral Blood Stem Cell Transplantation', Biology of Blood and Marrow Transplantation, vol. 17, no. 6, pp. 885-892. https://doi.org/10.1016/j.bbmt.2010.09.012

@article{4f237bd26e7d40fd8bbdae800f6f6e79,

title = "HLA-C Antigen Mismatch Is Associated with Worse Outcome in Unrelated Donor Peripheral Blood Stem Cell Transplantation",

abstract = "The association between HLA matching and outcome in unrelated-donor peripheral blood stem cell (PBSC) transplantation has not yet been established. In the present study, a total of 1933 unrelated donor-recipient pairs who underwent PBSC transplantation between 1999 and 2006 for acute myelogenous leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, or chronic myelogenous leukemia and received high-resolution HLA typing for HLA-A, -B, -C, -DRB1, -DQA1, and -DQB1 were included in the analysis. Outcomes were compared between HLA-matched and HLA-mismatched pairs, adjusting for patient and transplant characteristics. Matching for HLA-A, -B, -C, and -DRB1 alleles (8/8 match) was associated with better survival at 1 year compared with 7/8 HLA-matched pairs (56\% vs 47\%). Using 8/8 HLA-matched patients as the baseline (n = 1243), HLA-C antigen mismatches (n = 189) were statistically significantly associated with lower leukemia-free survival (relative risk [RR], 1.36; 95\% confidence interval [CI], 1.13-1.64; P = .0010), and increased risk for mortality (RR, 1.41; 95\% CI, 1.16-1.70; P = .0005), treatment-related mortality (RR, 1.61; 95\% CI, 1.25-2.08; P = .0002), and grade III-IV graft-versus-host disease (RR, 1.98; 95\% CI, 1.50-2.62; P < .0001). HLA-B antigen or allele mismatching was associated with an increased risk for acute GVHD grade III-IV. No statistically significant differences in outcome were observed for HLA-C allele (n = 61), HLA-A antigen/allele (n = 136), HLA-DRB1 allele (n = 39), or HLA-DQ antigen/allele (n = 114) mismatches compared with 8/8 HLA-matched pairs. HLA mismatch was not associated with relapse or chronic GVHD. HLA-C antigen-mismatched unrelated PBSC donors were associated with worse outcomes compared with 8/8 HLA-matched donors. The study's limited power due to small sample size precludes conclusions about other mismatches.",

keywords = "Disease free survival, Graft-vs-Host disease, HLA Mismatch, HLA-C antigen, Hematopoietic cell transplantation",

author = "Ann Woolfrey and Klein, \{John P.\} and Michael Haagenson and Stephen Spellman and Effie Petersdorf and Machteld Oudshoorn and James Gajewski and Hale, \{Gregory A.\} and John Horan and Minoo Battiwalla and Marino, \{Susana R.\} and Michelle Setterholm and Olle Ringden and Carolyn Hurley and Neal Flomenberg and Claudio Anasetti and Marcelo Fernandez-Vina and Lee, \{Stephanie J.\}",

note = "Funding Information: Financial disclosure: The CIBMTR is supported by Public Health Service Grant/Cooperative Agreement U24-CA76518 from the National Cancer Institute (NCI) , the National Heart, Lung and Blood Institute (NHLBI) , and the National Institute of Allergy and Infectious Diseases ; NHLBI-NCI Grant/Cooperative Agreement 5U01HL069294 ; Health Resources and Services Administration Contract HHSH234200637015C ; Office of Naval Research Grants N00014-06-1-0704 and N00014-08-1-0058 ; and grants from AABB, Aetna, American Society for Blood and Marrow Transplantation, Amgen Inc, anonymous donation to the Medical College of Wisconsin, Astellas Pharma US Inc, Baxter International Inc, Bayer HealthCare Pharmaceuticals, Be the Match Foundation, Biogen IDEC, BioMarin Pharmaceutical Inc, Biovitrum AB, BloodCenter of Wisconsin, Blue Cross and Blue Shield Association, Bone Marrow Foundation, Canadian Blood and Marrow Transplant Group, CaridianBCT, Celgene Corporation, CellGenix GmbH, Centers for Disease Control and Prevention, Children{\textquoteright}s Leukemia Research Association, ClinImmune Labs, CTI Clinical Trial and Consulting Services, Cubist Pharmaceuticals, Cylex Inc, CytoTherm, DOR BioPharma Inc, Dynal Biotech (an Invitrogen company), Eisai Inc, Enzon Pharmaceuticals Inc, European Group for Blood and Marrow Transplantation, Gamida Cell Ltd, GE Healthcare, Genentech Inc, Genzyme Corporation, Histogenetics Inc, HKS Medical Information Systems, Hospira Inc, Infectious Diseases Society of America, Kiadis Pharma, Kirin Brewery Co Ltd, Leukemia \& Lymphoma Society, Merck \& Company, Medical College of Wisconsin, MGI Pharma Inc, Michigan Community Blood Centers, Millennium Pharmaceuticals Inc, Miller Pharmacal Group, Milliman USA Inc, Miltenyi Biotec Inc, National Marrow Donor Program, Nature Publishing Group, New York Blood Center, Novartis Oncology, Oncology Nursing Society, Osiris Therapeutics Inc, Otsuka America Pharmaceutical Inc, Pall Life Sciences, Pfizer Inc, Saladax Biomedical Inc, Schering Corporation, Society for Healthcare Epidemiology of America, Soligenix Inc, StemCyte Inc, StemSoft Software Inc, Sysmex America Inc, THERAKOS Inc, Thermogenesis Corporation, Vidacare Corporation, Vion Pharmaceuticals Inc, ViraCor Laboratories, ViroPharma Inc, and Wellpoint Inc . The views expressed in this article do not reflect the official policy or position of the National Institutes of Health, Department of the Navy, Department of Defense, or any other agency of the US Government. ",

year = "2011",

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doi = "10.1016/j.bbmt.2010.09.012",

language = "English (US)",

volume = "17",

pages = "885--892",

journal = "Biology of Blood and Marrow Transplantation",

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T1 - HLA-C Antigen Mismatch Is Associated with Worse Outcome in Unrelated Donor Peripheral Blood Stem Cell Transplantation

AU - Woolfrey, Ann

AU - Klein, John P.

AU - Haagenson, Michael

AU - Spellman, Stephen

AU - Petersdorf, Effie

AU - Oudshoorn, Machteld

AU - Gajewski, James

AU - Hale, Gregory A.

AU - Horan, John

AU - Battiwalla, Minoo

AU - Marino, Susana R.

AU - Setterholm, Michelle

AU - Ringden, Olle

AU - Hurley, Carolyn

AU - Flomenberg, Neal

AU - Anasetti, Claudio

AU - Fernandez-Vina, Marcelo

AU - Lee, Stephanie J.

N1 - Funding Information: Financial disclosure: The CIBMTR is supported by Public Health Service Grant/Cooperative Agreement U24-CA76518 from the National Cancer Institute (NCI) , the National Heart, Lung and Blood Institute (NHLBI) , and the National Institute of Allergy and Infectious Diseases ; NHLBI-NCI Grant/Cooperative Agreement 5U01HL069294 ; Health Resources and Services Administration Contract HHSH234200637015C ; Office of Naval Research Grants N00014-06-1-0704 and N00014-08-1-0058 ; and grants from AABB, Aetna, American Society for Blood and Marrow Transplantation, Amgen Inc, anonymous donation to the Medical College of Wisconsin, Astellas Pharma US Inc, Baxter International Inc, Bayer HealthCare Pharmaceuticals, Be the Match Foundation, Biogen IDEC, BioMarin Pharmaceutical Inc, Biovitrum AB, BloodCenter of Wisconsin, Blue Cross and Blue Shield Association, Bone Marrow Foundation, Canadian Blood and Marrow Transplant Group, CaridianBCT, Celgene Corporation, CellGenix GmbH, Centers for Disease Control and Prevention, Children’s Leukemia Research Association, ClinImmune Labs, CTI Clinical Trial and Consulting Services, Cubist Pharmaceuticals, Cylex Inc, CytoTherm, DOR BioPharma Inc, Dynal Biotech (an Invitrogen company), Eisai Inc, Enzon Pharmaceuticals Inc, European Group for Blood and Marrow Transplantation, Gamida Cell Ltd, GE Healthcare, Genentech Inc, Genzyme Corporation, Histogenetics Inc, HKS Medical Information Systems, Hospira Inc, Infectious Diseases Society of America, Kiadis Pharma, Kirin Brewery Co Ltd, Leukemia & Lymphoma Society, Merck & Company, Medical College of Wisconsin, MGI Pharma Inc, Michigan Community Blood Centers, Millennium Pharmaceuticals Inc, Miller Pharmacal Group, Milliman USA Inc, Miltenyi Biotec Inc, National Marrow Donor Program, Nature Publishing Group, New York Blood Center, Novartis Oncology, Oncology Nursing Society, Osiris Therapeutics Inc, Otsuka America Pharmaceutical Inc, Pall Life Sciences, Pfizer Inc, Saladax Biomedical Inc, Schering Corporation, Society for Healthcare Epidemiology of America, Soligenix Inc, StemCyte Inc, StemSoft Software Inc, Sysmex America Inc, THERAKOS Inc, Thermogenesis Corporation, Vidacare Corporation, Vion Pharmaceuticals Inc, ViraCor Laboratories, ViroPharma Inc, and Wellpoint Inc . The views expressed in this article do not reflect the official policy or position of the National Institutes of Health, Department of the Navy, Department of Defense, or any other agency of the US Government.

PY - 2011/6/1

Y1 - 2011/6/1

N2 - The association between HLA matching and outcome in unrelated-donor peripheral blood stem cell (PBSC) transplantation has not yet been established. In the present study, a total of 1933 unrelated donor-recipient pairs who underwent PBSC transplantation between 1999 and 2006 for acute myelogenous leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, or chronic myelogenous leukemia and received high-resolution HLA typing for HLA-A, -B, -C, -DRB1, -DQA1, and -DQB1 were included in the analysis. Outcomes were compared between HLA-matched and HLA-mismatched pairs, adjusting for patient and transplant characteristics. Matching for HLA-A, -B, -C, and -DRB1 alleles (8/8 match) was associated with better survival at 1 year compared with 7/8 HLA-matched pairs (56% vs 47%). Using 8/8 HLA-matched patients as the baseline (n = 1243), HLA-C antigen mismatches (n = 189) were statistically significantly associated with lower leukemia-free survival (relative risk [RR], 1.36; 95% confidence interval [CI], 1.13-1.64; P = .0010), and increased risk for mortality (RR, 1.41; 95% CI, 1.16-1.70; P = .0005), treatment-related mortality (RR, 1.61; 95% CI, 1.25-2.08; P = .0002), and grade III-IV graft-versus-host disease (RR, 1.98; 95% CI, 1.50-2.62; P < .0001). HLA-B antigen or allele mismatching was associated with an increased risk for acute GVHD grade III-IV. No statistically significant differences in outcome were observed for HLA-C allele (n = 61), HLA-A antigen/allele (n = 136), HLA-DRB1 allele (n = 39), or HLA-DQ antigen/allele (n = 114) mismatches compared with 8/8 HLA-matched pairs. HLA mismatch was not associated with relapse or chronic GVHD. HLA-C antigen-mismatched unrelated PBSC donors were associated with worse outcomes compared with 8/8 HLA-matched donors. The study's limited power due to small sample size precludes conclusions about other mismatches.

AB - The association between HLA matching and outcome in unrelated-donor peripheral blood stem cell (PBSC) transplantation has not yet been established. In the present study, a total of 1933 unrelated donor-recipient pairs who underwent PBSC transplantation between 1999 and 2006 for acute myelogenous leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, or chronic myelogenous leukemia and received high-resolution HLA typing for HLA-A, -B, -C, -DRB1, -DQA1, and -DQB1 were included in the analysis. Outcomes were compared between HLA-matched and HLA-mismatched pairs, adjusting for patient and transplant characteristics. Matching for HLA-A, -B, -C, and -DRB1 alleles (8/8 match) was associated with better survival at 1 year compared with 7/8 HLA-matched pairs (56% vs 47%). Using 8/8 HLA-matched patients as the baseline (n = 1243), HLA-C antigen mismatches (n = 189) were statistically significantly associated with lower leukemia-free survival (relative risk [RR], 1.36; 95% confidence interval [CI], 1.13-1.64; P = .0010), and increased risk for mortality (RR, 1.41; 95% CI, 1.16-1.70; P = .0005), treatment-related mortality (RR, 1.61; 95% CI, 1.25-2.08; P = .0002), and grade III-IV graft-versus-host disease (RR, 1.98; 95% CI, 1.50-2.62; P < .0001). HLA-B antigen or allele mismatching was associated with an increased risk for acute GVHD grade III-IV. No statistically significant differences in outcome were observed for HLA-C allele (n = 61), HLA-A antigen/allele (n = 136), HLA-DRB1 allele (n = 39), or HLA-DQ antigen/allele (n = 114) mismatches compared with 8/8 HLA-matched pairs. HLA mismatch was not associated with relapse or chronic GVHD. HLA-C antigen-mismatched unrelated PBSC donors were associated with worse outcomes compared with 8/8 HLA-matched donors. The study's limited power due to small sample size precludes conclusions about other mismatches.

KW - Disease free survival

KW - Graft-vs-Host disease

KW - HLA Mismatch

KW - HLA-C antigen

KW - Hematopoietic cell transplantation

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UR - https://www.scopus.com/pages/publications/79955985682#tab=citedBy

U2 - 10.1016/j.bbmt.2010.09.012

DO - 10.1016/j.bbmt.2010.09.012

M3 - Article

C2 - 20870028

AN - SCOPUS:79955985682

SN - 1083-8791

VL - 17

SP - 885

EP - 892

JO - Biology of Blood and Marrow Transplantation

JF - Biology of Blood and Marrow Transplantation

IS - 6

ER -

HLA-C Antigen Mismatch Is Associated with Worse Outcome in Unrelated Donor Peripheral Blood Stem Cell Transplantation

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