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High-Resolution Donor-Recipient HLA Matching Does Not Influence Acute or Chronic Gvhd in Umbilical Cord Blood Transplantation

Track: Poster Abstracts
Wednesday, February 26, 2014, 6:45 PM-7:45 PM
Longhorn Hall E (Exhibit Level 1) (Gaylord Texan)
Aleksandr Lazaryan, MD PhD , Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, MN
John E. Wagner, MD , Pediatric Blood and Marrow Transplantation, University of Minnesota, Minneapolis, MN
Claudio Brunstein, MD, PhD , Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, MN
Todd Defor, MS , BMT Research Program, University of Minnesota, Minneapolis, MN
Margaret L. MacMillan, MD, MSc , Pediatric Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, MN
Bruce R. Blazar, MD , Pediatric Blood and Marrow Transplantation, University of Minnesota, Minneapolis, MN
Daniel J. Weisdorf, MD , University of Minnesota, Minneapolis, MN
Mukta Arora, MD, MS , Hematology, Oncology and Transplant, University of Minnesota, Minneapolis, MN

The degree of antigen-level (HLA-A, -B) and allele-level HLA-DRB1 matching has been correlated with the risk of acute GVHD (aGVHD) in prior studies of umbilical cord blood transplantation (UCBT), however no impact of HLA matching on development of chronic GVHD (cGVHD) has been reported for ≥4/6-matched UCBT. To understand the impact of high-resolution HLA allele matching at -A, -B, -C, -DRB1 and -DQ loci on GVHD we studied 404 recipients of single- (n=129) and double-unit (n=275, based on the predominating unit) UCBT from 2000 to 2010. Overall cumulative incidence of grade II-IV aGVHD, grade III-IV aGVHD, and cGVHD was 47%, 18%, and 20%, respectively. HLA allele-matched recipients, grouped as 9-10/10 (17%), 6-8/10 (61%), and <6/10 (22%), had a similar cumulative incidence of grade II-IV (43% vs. 47% vs. 52%, p=0.5) or grade III-IV (17% vs. 16% vs. 22%, p=0.4) aGVHD, respectively. In multivariable analysis HLA matching did not influence grade II-IV and III-IV aGVHD  (all p>0.5) after adjustment for the number of units, CD3, CD34 dose, age, gender match, conditioning, recipient CMV status, ATG use, and the year of transplant (Table). Use of ATG was independently associated with a lower risk of grade II-IV aGVHD (relative risk [RR]=0.5, p<0.01). Univariate difference in cumulative incidence of cGVHD for 9-10/10 (17%), 6-8/10 (17%), and <6/10 (29%) HLA match was confounded by age (RR=3.4 for ≥18 years, p<0.01) and prior aGVHD (RR=2.3, p<0.01) in multivariable analysis adjusted for CD34, CD3 dose, and the number of cord units. No other factors influenced cGVHD or modified the risk of HLA matching on cGVHD. Similar results were found in a multivariable analysis for stratified single- and double-unit UCBT. We conclude that stringent high-resolution HLA matching at -A, -B, -C, -DRB1 and -DQ loci does not influence the incidence of acute or chronic GVHD among recipients of UCBT.

Relative risk* of acute and chronic GVHD based on degree of high-resolution HLA matching

Factor

RR of aGVHD (95% CI)

RR of cGVHD (95% CI)

(n=79)

Grade II-IV

(n=191)

Grade III-IV

(n=72)

HLA match**

9-10/10 (n=69)

6-8/10 (n=246)

<6/10 (n=89)

1.0

1.1 (0.7-1.8)

1.1 (0.7-2.0)

1.0

1.1 (0.5-2.5)

1.4 (0.6-3.3)

1.0

0.7 (0.3-1.5)

1.1 (0.1-2.5)

*Adjusted for age, gender match, year of transplant, number of units, CD3, CD34 dose, ATG use, conditioning, recipient CMV status, prior aGVHD as appropriate; **High-resolution allele match at HLA-A, -B, -C, -DRB1, and -DQ loci; RR, relative risk; CI, confidence interval

Disclosures:
Nothing To Disclose
See more of: Poster Session 1: Histocompatibility/Alternative Stem Cell Sources
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