Immune responses and clinical outcome of massive human osteoarticular allografts

Cell mediated immune responses as measured by lymphocyte proliferation induced by the mitogens phytohemagglutinin and concanavalin A and antigen extracts of donor derived bone were studied within 2 years after wide resection of bone tumors in 18 patients receiving fresh frozen massive osteoarticular allografts. No uniform changes were seen in mitogen induced responses in 18 patients. However, five of nine patients tested with antigen extracts of donor derived bone showed elevated immune responses, one moderate and four weak. The incorporation of the allograft (evaluated by repeated radiographs; specific isotope techniques ; clinical outcome assessed by the functional rating scores of Mankin-Waber and the Musculoskeletal Tumor Society; and histologic biopsy findings on new bone formation) did not differ in these patients from those in patients without any response to donor derived tissue. During a long term followup (mean, 11 years; range, 2-20 years), degenerative joint and sclerotic density bone changes developed after 2 to 4 years without correlation to immune responses. Histologic specimens showed no signs of immunologic reaction, and no clinical rejection episodes were recorded. A slightly variable immune response to allograft bone seems to occur, but its clinical significance for outcome of the grafts remains to be determined. The low immune responses might reflect a low antigen release rate through an indirect pathway or immunologic tolerance to antigens or proteins shed from massive allografts that are nonliving scaffold implants during the creeping substitution process, corresponding to the low immune response and the slow histologic repair.