HLA sensitization and allograft bone graft incorporation

Abstract

Achieving union between host bone and massive structural allografts can be difficult. Donor and recipient human leukocyte antigen (HLA) mismatches and recipient antibody response to donor HLA antigens might affect union. In a prospective multiinstitutional study, we enrolled a consecutive series of patients receiving cortex-replacing, massive structural bone allografts to determine the rate of donor-specific HLA antibody sensitization and to investigate the potential effect of such HLA alloantibody sensitization on allograft incorporation. HLA typing of patients and donors was determined by molecular typing methods. Donor-specific HLA sensitization occurred in 57% of the patients but had no demonstrable effect on graft incorporation or union. The type of host-allograft junction did have a major effect on graft incorporation. Cortical-to-cortical allograft-to-host junctions healed more slowly (mean, 542 days) than corticocancellous to corticocancellous allograft-to-host junctions (mean, 243 days). Although HLA sensitization does not appear to delay structural allograft bone incorporation, further followup is required to determine if there is an association between HLA sensitization and long-term graft survival. Based on these preliminary data, measures to further minimize or modulate HLA sensitization or response are not indicated at present for the purposes of improving structural bone allograft union.

Level of evidence: Level II, prognostic study.

Fig. 1

This log rank survivorship analysis compares those who developed HLA antibodies (hla = POS) with those who did not develop HLA-specific antibodies (hla = NEG) for the overall group of all patients. Note the lack of difference between the two curves reflecting the lack of HLA effect on the ultimate healing times overall (p = nonsignificant).

Fig. 2

This log rank survivorship analysis reveals no difference in the curves comparing healing-free survivorship of all cortical-to-cortical junctions when grouped by those who developed donor-specific HLA antibodies (hla = POS) versus those who did not develop donor-specific antibodies (hla = NEG) (p = nonsignificant).

Fig. 3

This log rank survivorship analysis reveals no difference in the curves comparing healing-free survivorship of all corticocancellous to corticocancellous junctions when grouped by those who developed donor-specific HLA antibodies (hla = POS) versus those who did not develop donor-specific antibodies (hla = NEG) (p = nonsignificant).

Fig. 4

This log rank survivorship analysis depicts the difference between the cortical-to-cortical junctions versus the corticocancellous to corticocancellous junctions analyzing only those patients who developed donor-specific HLA antibodies. Note the more rapid (p = 0.027) healing of the corticocancellous junctions.

Fig. 5

This log rank survivorship analysis depicts the more delayed healing of the cortical-to-cortical junctions compared with the corticocancellous to corticocancellous junctions analyzing only those patients who did not develop donor-specific HLA antibodies (p = 0.0017).

Fig. 6

This log rank survivorship analysis depicts all four curves, including cortical-to-cortical junctions compared with corticocancellous junctions also considering those that developed donor-specific HLA antibodies (hla = POS) and those that did not develop donor-specific HLA antibodies (hla = NEG). The curves clearly demonstrate that the segregation is based on the junctional type rather than the HLA antibody status (p = 0.0014).

Fig. 7

This log rank survivorship graph depicts the difference between cortical-to-cortical junctions versus corticocancellous to corticocancellous junctions considering the entire cohort without regard to HLA status. It clearly demonstrates the difference (p = 0.0002) between healing of the two groups with the more rapid healing of the corticocancellous junctions.

Fig. 8

This log rank survivorship analysis demonstrates there in no effect on time to allograft healing comparing those that develop HLA antibodies (hla = POS) with those that do not develop HLA antibodies (hla = NEG) even when the definition of radiographic healing is expanded to include the categories of “possibly healed” in addition to “completely healed” and “probably healed.”

Fig. 9

This log rank survivorship analysis of cortical to cortical junction healing times, including completely healed, probably healed, and possibly healed in the radiographic definition of healing, again confirms an absence of any detectable effect of HLA sensitization (hla = POS) or the lack of HLA sensitization (hla = NEG) on healing in cortical junctions.

Fig. 10

This log rank survivorship analysis on the timing of healing of corticocancellous to corticocancellous junctions includes completely healed, probably healed, and possibly healed in the definition of healing. There is no detectable effect of HLA sensitization (hla = POS) or the lack thereof (hla = NEG) on time to allograft healing in these corticocancellous junction sites.

Fig. 11

This series of log rank survivorship curves, stratified by cortical-to-cortical junctions and corticocancellous to corticocancellous junctions as well as HLA-positive status (hla = POS) and HLA-negative status (hla = NEG), clearly demonstrates that the only factor effecting healing is the junctional type. The corticocancellous to corticocancellous junctions healed faster (p = 0.0001) than the cortical-to-cortical junctions.