Effect of Prior Blood Transfusions on Marrow Grafts: Abrogation of Sensitization by Procarbazine and Antithymocyte Serum

Abstract

Previous studies have shown that a single blood transfusion can immunize a dog and lead to rejection of a subsequent marrow graft even when donor and recipient are littermates matched at the major histocompatibility complex (DL-A). The present study was designed to evaluate whether immunization of a marrow graft recipient by prior blood transfusions could be abrogated by procarbazine and/or antithymocyte serum. On day 0, recipient dogs were given 1200 R total body irradiation followed by marrow from DL-A incompatible unrelated donors of different breed. All recipients were transfused with blood from the marrow donor on days -20 and -13 before irradiation. Group 1: seven of 10 dogs given no further therapy rejected the marrow graft. Group 2: four of eight dogs given procarbazine 12.5 mg/kg i.v. on days -8, -6 and -4 rejected. Group 3: five of 10 dogs given anti-dog thymocyte serum (ATS), 0.6 ml/kg subcutaneously on days -7, -5, and -3 rejected. Group 4: one of 10 dogs given procarbazine, 12.5 mg/kg i.v. on days -8, -6, and -4 and ATS, 0.6 ml/kg subcutaneously on days -7, -5, and -3 rejected the graft. Nine had sustained engraftment. Group 5: six of six dogs given the combination of procarbazine and ATS and further donor transfusions on days -6, -4, and -2 rejected. It was concluded that immunization by preceding blood transfusions can be successfully abrogated by a combination of procarbazine and ATS (p < 0.01). ATS or procarbazine alone were not sufficient. Continuation of donor blood transfusions during the procarbazine-ATS regimen precluded successful engraftment.