INDUCTION OF GRAFT-VERSUS-HOST DISEASE AS IMMUNOTHERAPY FOR RELAPSED CHRONIC MYELOID-LEUKEMIA

Background. The ability of allogeneic bone marrow transplantation to c ure chronic myeloid leukemia (CML) is due to both the conditioning reg imen and the antileukemic effects of the lymphocytes in the grafted ma rrow. We studied the ability of interferon alfa-2b and infusions of mo nonuclear cells from the marrow donor to induce a graft-versus-leukemi a reaction in patients with CML in relapse after bone marrow transplan tation. Methods. Eleven patients with relapsed CML after allogeneic bo ne marrow transplantation were treated with interferon alfa-2b and inf usions of mononuclear cells. The patients were monitored for toxic eff ects, for hematologic and cytogenetic responses, and, with use of the polymerase chain reaction, for elimination of cells containing the bcr /abl messenger RNA transcript characteristic of the leukemic cells. Re sults. Six of the eight patients with stable CML after relapse had com plete remissions according to molecular genetic criteria, since no cel ls with bcr/abl messenger RNA transcripts were detected (the method ca n identify 1 leukemic cell among 1 million normal cells). The three pa tients with accelerated CML after relapse did not enter remission. Mye losuppression was prominent in eight patients. Grade I acute graft-ver sus-host disease (GVHD) occurred in six patients, and grade III acute GVHD occurred in three. Limited chronic GVHD developed in five patient s. Conclusions. The induction of a graft-versus-leukemia reaction with interferon alfa-2b and infusions of donor mononuclear cells in patien ts with CML in relapse after bone marrow transplantation is an effecti ve antileukemic therapy that may off er an alternative to a second mar row transplantation.