RT Journal Article
A1 Eapen, Mary
A1 Klein, John
A1 Sanz, Guillermo
A1 Anasetti, Claudio
A1 Garcia, Joan
A1 Gluckman, Eliane
A1 Horowitz, Mary M.
A1 Koegler, Gesine
A1 Laughlin, Mary
A1 Michel, Gerard
A1 Spellman, Stephen R
A1 Smith, Franklin O.
A1 Rocha, Vanderson
T1 Donor-Recipient Matching at the HLA-C Locus and Early Outcomes after Unrelated Umbilical Cord Blood Transplant (UCBT)
JF Blood
JO Blood
YR 2008
DO 10.1182/blood.V112.11.153.153
VO 112
IS 11
SP 153
OP 153
SN 0006-4971
AB Previous studies indicate unrelated donor bone marrow transplantation mismatched at HLA-C locus (antigen-level but not allele-level) result in higher acute graft-versus-host disease (GVHD) and mortality. Hematopoietic recovery is not affected by mismatching at this locus. The current selection of cord blood units is based on antigen-level HLA typing at HLA A and B and allele-level at DRB1. The relative importance of matching at HLA-C has not yet been described for unrelated UCBT. To address this question we analyzed hematopoietic recovery, acute GVHD and mortality in 619 UCBT recipients who received a single cord blood (CB) unit, a myeloablative preparative regimen and a calcinuerin inhibitor for GVHD prophylaxis. Eighty-three percent of patients received UCBT for leukemia or lymphoma and 17% for immunologic, metabolic or histiocytic diseases. Seventy percent of patients were ≤16 years of age at transplantation. HLA typing (using molecular methods) was performed for 96% (n=593) of donor-recipient pairs. Method of typing is not available for the remaining 4% (n=26). For all analysis, donor-recipient HLA matching was evaluated at the antigen-level (first 2 of 4 digits) for HLA-A, B, C and allele-level (4 digits) for DRB1. The median infused cell dose was 4 × 107/kg and median follow-up, 2 years. We first examined the effect of donor-recipient HLA matching and cell dose on hematopoietic recovery and mortality considering the current standard for selection of cord blood units. Fifteen percent (n=94) were matched at HLA A, B and DRB1, with 43% (n=265) mismatched at 1-locus and 42% (n=260) mismatched at 2-loci. As reported previously, compared to matched UCBT, neutrophil recovery at day-42 was lower after UCBT mismatched at 1-locus (RR 0.48, p=0.042) and 2-loci (RR 0.38, p=0.007). After adjusting for infused cell dose, year of transplant and disease status, platelet recovery and 1-year mortality rates were not different after matched and mismatched UCBT. We then examined whether the addition of another mismatch at the C locus impacted outcomes. The Table below shows the probabilities of hematopoietic recovery, acute GVHD and survival considering matching at the C-locus in addition to the standard criteria used for CB unit selection. The comparison groups for each of the categories below are patients who received UCBT matched at the C locus for the respective category. In conclusion, the data shown suggest HLA-C does not affect hematopoietic recovery, acute GVHD and 1-year overall survival after UCBT. However, definitive conclusions can only be achieved in a larger series. In the mean time, cord blood unit selection need not consider matching at the C-locus.OutcomesProbabilityp-valueNeutrophil recovery at day-42Matched at A, B, DRB1 + mismatch at C (n=22) vs. matched at C (n=72)82% vs. 93%0.241-locus mismatch at A, B, DRB1 + mismatch at C (n=162) vs. matched at C (n=103)81% vs. 85%0.342-loci mismatch at A, B, DRB1 + mismatch at C (n=217) vs. matched at C (n=43)77% vs. 77%0.98Platelet recovery at day-100Matched at A, B, DRB1 + mismatch at C (n=22) vs. matched at C (n=72)72% vs. 68%0.681-locus mismatch at A, B, DRB1 + mismatch at C (n=162) vs. matched at C (n=103)61% vs. 66%0.352-loci mismatch at A, B, DRB1 + mismatch at C (n=217) vs. matched at C (n=43)54% vs. 58%0.59Acute grade 2–4 GVHD at day-100Matched at A, B, DRB1 + mismatch at C (n=21) vs. matched at C (n=71)32% vs. 40%0.481-locus mismatch at A, B, DRB1 + mismatch at C (n=162) vs. matched at C (n=101)36% vs. 42%0.392-loci mismatch at A, B, DRB1 + mismatch at C (n=213) vs. matched at C (n=43)35% vs. 40%0.61Overall survival at 1-yearMatched at A, B, DRB1 + mismatch at C (n=22) vs. matched at C (n=72)55% vs. 59%0.741-locus mismatch at A, B, DRB1 + mismatch at C (n=162) vs. matched at C (n=103)57% vs. 59%0.742-loci mismatch at A, B, DRB1 + mismatch at C (n=217) vs. matched at C (n=43)52% vs. 53%0.89
RD 11/15/2025
UL https://doi.org/10.1182/blood.V112.11.153.153