High resolution HLA matching associated with decreased mortality after unrelated bone marrow transplantation.
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.
Speiser
D E
DE
Laboratoire National de Référence pour l'Histocompatibilité, Hôpital Cantonal Universitaire de Genève, Switzerland.
Tiercy
J M
JM
Rufer
N
N
Grundschober
C
C
Gratwohl
A
A
Chapuis
B
B
Helg
C
C
Löliger
C C
CC
Siren
M K
MK
Roosnek
E
E
Jeannet
M
M
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
D006680:HLA Antigens