title: High resolution HLA matching associated with decreased mortality after unrelated bone marrow transplantation.
abstract: As compared with related HLA-identical sibling donors, bone marrow transplantation (BMT) with phenotypically HLA ABDR-compatible unrelated donors is associated with increased mortality. This may be due to hidden HLA incompatibilities not detected by conventional typing. We have analyzed 44 unrelated patient-donor pairs who were matched for HLA-A, -B, and -DR by routine tissue typing. Our comprehensive HLA typing approach consisted of serology, cytotoxic T-cell precursor (CTLp) tests, T-cell cloning, oligotyping, and DNA sequencing. Using these techniques, we identified numerous HLA allele mismatches not detected by the previously applied routine typing. Twenty-four patient-donor pairs were highly matched and had a low CTLp frequency, whereas the remaining 20 pairs were allele-mismatched for HLA-A, -B, -C, -DR, -DQ antigens and/or had a positive result of the CTLp test. Patient and donor age, diagnosis, and treatment did not differ significantly between the matched and mismatched transplants. The probability for severe acute graft-versus-host disease grades III-IV was 21% in the matched and 47% in the mismatched patients (P = .0464). Transplant-related mortality was 21% and 57% (P = .0072) and actuarial patient survival rates at 3 years were 61% and 13% (P = .0005). We conclude that both HLA class I and class II allele mismatches between unrelated phenotypically ABDR-compatible patient-donor pairs are frequent and associated with increased incidence of posttransplant complications.
authors.affiliation: Laboratoire National de Référence pour l'Histocompatibilité, Hôpital Cantonal Universitaire de Genève, Switzerland.
authors.forename: D E
authors.initials: DE
authors.lastname: Speiser
authors.forename: J M
authors.initials: JM
authors.lastname: Tiercy
authors.forename: N
authors.initials: N
authors.lastname: Rufer
authors.forename: C
authors.initials: C
authors.lastname: Grundschober
authors.forename: A
authors.initials: A
authors.lastname: Gratwohl
authors.forename: B
authors.initials: B
authors.lastname: Chapuis
authors.forename: C
authors.initials: C
authors.lastname: Helg
authors.forename: C C
authors.initials: CC
authors.lastname: Löliger
authors.forename: M K
authors.initials: MK
authors.lastname: Siren
authors.forename: E
authors.initials: E
authors.lastname: Roosnek
authors.forename: M
authors.initials: M
authors.lastname: Jeannet
mesh_terms: D000483:Alleles; D016026:Bone Marrow Transplantation / Q000276:immunology / Q000401:mortality*; D002423:Cause of Death; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000276:immunology / Q000401:mortality / Q000517:prevention & control; D006680:HLA Antigens / Q000032:analysis / Q000276:immunology; D006650:Histocompatibility Testing / Q000379:methods*; D006801:Humans; D007239:Infections / Q000209:etiology / Q000401:mortality; D015993:Life Tables; D008297:Male; D016019:Survival Analysis; D015996:Survival Rate; D014184:Transplantation, Homologous / Q000276:immunology / Q000401:mortality
chemical_list: D006680:HLA Antigens