Allele-level HLA matching for umbilical cord blood transplantation for non-malignant diseases in children: a retrospective analysis.
Abstract
<h4>Background</h4>The standard for selecting unrelated umbilical cord blood units
for transplantation for non-malignant diseases relies on antigen-level (lower resolution)
HLA typing for HLA-A and HLA-B, and allele-level for HLA-DRB1. We aimed to study the
effects of allele-level matching at a higher resolution-HLA-A, HLA-B, HLA-C, and HLA-DRB1,
which is the standard used for adult unrelated volunteer donor transplantation for
non-malignant diseases-for umbilical cord blood transplantation.<h4>Methods</h4>We
retrospectively studied 1199 paediatric donor-recipient pairs with allele-level HLA
matching who received a single unit umbilical cord blood transplantation for non-malignant
diseases reported to the Center for International Blood and Marrow Transplant Research
or Eurocord and European Group for Blood and Marrow Transplant. Transplantations occurred
between Jan 1, 2000, and Dec 31, 2012. The primary outcome was overall survival. The
effect of HLA matching on survival was studied using a Cox regression model.<h4>Findings</h4>Compared
with HLA-matched transplantations, mortality was higher with transplantations mismatched
at two (hazard ratio [HR] 1·55, 95% CI 1·08-2·21, p=0·018), three (2·04, 1·44-2·89,
p=0·0001), and four or more alleles (3·15, 2·16-4·58, p<0·0001). There were no significant
differences in mortality between transplantations that were matched and mismatched
at one allele (HR 1·18, 95% CI 0·80-1·72, p=0·39). Other factors associated with higher
mortality included recipient cytomegalovirus seropositivity (HR 1·40, 95% CI 1·13-1·74,
p=0·0020), reduced intensity compared with myeloablative conditioning regimens (HR
1·36, 1·10-1·68, p=0·0041), transplantation of units with total nucleated cell dose
of more than 21 × 10<sup>7</sup> cells per kg compared with 21 × 107 cells per kg or less (HR 1·47, 1·11-1·95, p=0·0076), and transplantations done in
2000-05 compared with those done in 2006-12 (HR 1·64, 1·31-2·04, p<0·0001). The 5-year
overall survival adjusted for recipient cytomegalovirus serostatus, conditioning regimen
intensity, total nucleated cell dose, and transplantation period was 79% (95% CI 74-85)
after HLA matched, 76% (71-81) after one allele mismatched, 70% (65-75) after two
alleles mismatched, 62% (57-68) after three alleles mismatched, and 49% (41-57) after
four or more alleles mismatched transplantations. Graft failure was the predominant
cause of mortality.<h4>Interpretation</h4>These data support a change from current
practice in that selection of unrelated umbilical cord blood units for transplantation
for non-malignant diseases should consider allele-level HLA matching at HLA-A, HLA-B,
HLA-C, and HLA-DRB1.<h4>Funding</h4>National Cancer Institute; National Heart, Lung,
and Blood Institute; National Institute for Allergy and Infectious Diseases; US Department
of Health and Human Services-Health Resources and Services Administration; and US
Department of Navy.
Type
Journal articleSubject
Fetal BloodHumans
Histocompatibility Testing
Treatment Outcome
Survival Analysis
Retrospective Studies
Alleles
Adolescent
Child
Child, Preschool
Infant
Female
Male
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https://hdl.handle.net/10161/24620Published Version (Please cite this version)
10.1016/s2352-3026(17)30104-7Publication Info
Eapen, Mary; Wang, Tao; Veys, Paul A; Boelens, Jaap J; St Martin, Andrew; Spellman,
Stephen; ... Ruggeri, Annalisa (2017). Allele-level HLA matching for umbilical cord blood transplantation for non-malignant
diseases in children: a retrospective analysis. The Lancet. Haematology, 4(7). pp. e325-e333. 10.1016/s2352-3026(17)30104-7. Retrieved from https://hdl.handle.net/10161/24620.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Joanne Kurtzberg
Jerome S. Harris Distinguished Professor of Pediatrics
Dr. Kurtzberg is an internationally renowned expert in pediatric hematology/oncology,
pediatric blood and marrow transplantation, umbilical cord blood banking and transplantation,
and novel applications of cord blood and birthing tissues in the emerging fields of
cellular therapies and regenerative medicine. Dr. Kurtzberg serves as the Director
of the Marcus Center for Cellular Cures (MC3), Director of the Pediatric Transplant
and Cellular Therapy Program, Director of the Carolina

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