The Impact of High-resolution HLA-A, HLA-B, HLA-C, and HLA-DRB1 on Transplant-related Outcomes in Single-unit Umbilical Cord Blood Transplantation in Pediatric Patients.
Current practice for selecting donor units for umbilical cord blood transplant (UCBT) involves matching at HLA-A and HLA-B by low-resolution typing and the HLA-DRB1 allele by high-resolution (HR) typing. We retrospectively studied the impact of HR allele matching at HLA-A, HLA-B, HLA-C, and HLA-DRB1 on transplant-related outcomes in 60 single-unit UCBTs in pediatric patients with malignant and nonmalignant conditions. Five-year overall survival of our cohort was 71% (95% confidence interval, 58-81); 27% experienced primary graft failure. Applying HR typing, donor-recipient mismatch variability increased ranging from 1/8 to 8/8, however, no impact on primary graft failure, graft-versus-host disease or posttransplant infection was observed. UCBTs with ≥6/8 HR matches did have a better overall survival (P=0.04) and decreased transplant-related mortality (P=0.02) compared with <6/8 HR matches. Using standard HLA typing, we showed an increased incidence of acute graft-versus-host disease (grade II to IV) and decreased transplant-related mortality in comparing the matched (6/6) versus ≤5/6 group (P=0.05 and 0.05, respectively). These data support the use of current guidelines for umbilical cord blood selection and encourage utilization of HR typing to select umbilical cord blood units matched at ≥6/8 especially when appropriate ≥5/6 units are available.
*Division of Hematology/Oncology/Stem Cell Transplant, Ann & Robert H. Lurie Children's Hospital of Chicago †Stem Cell Transplantation, Ann & Robert H. Lurie Children's Hospital of Chicago §Department of Pediatrics, Northwestern University Feinberg School of Medicine ‡Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL.
Amy E
AE
Armstrong
Eileen
E
Smyth
Irene B
IB
Helenowski
William T
WT
Tse
Reggie E
RE
Duerst
Jennifer
J
Schneiderman
Morris
M
Kletzel
Sonali
S
Chaudhury
D000208:Acute Disease; D000293:Adolescent; D000483:Alleles; D002648:Child; D002675:Child, Preschool; D036101:Cord Blood Stem Cell Transplantation / Q000009:adverse effects / Q000401:mortality; D005260:Female; D005805:Genes, MHC Class I; D005802:Genes, MHC Class II; D030342:Genetic Diseases, Inborn / Q000628:therapy; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control; D006680:HLA Antigens / Q000032:analysis* / Q000235:genetics; D059811:HLA-DRB1 Chains / Q000032:analysis* / Q000235:genetics; D006402:Hematologic Diseases / Q000628:therapy; D006650:Histocompatibility Testing / Q000379:methods*; D006801:Humans; D007223:Infant; D007239:Infections / Q000453:epidemiology / Q000209:etiology; D007518:Isoantibodies / Q000096:biosynthesis; D053208:Kaplan-Meier Estimate; D008297:Male; D009369:Neoplasms / Q000401:mortality / Q000628:therapy; D055031:Primary Graft Dysfunction / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control; D012008:Recurrence; D012189:Retrospective Studies; D016896:Treatment Outcome; D014775:Virus Activation
D006680:HLA Antigens; D059811:HLA-DRB1 Chains; D007518:Isoantibodies