Induction of Graft-versus-host Disease As Immunotherapy for Relapsed Chronic Myeloid Leukemia

Background: The ability of allogeneic bone marrow transplantation to cure chronic myeloid leukemia (CML) is due to both the conditioning regimen and the antileukemic effects of the lymphocytes in the grafted marrow. We studied the ability of interferon alfa-2b and infusions of mononuclear cells from the marrow donor to induce a graft-versus-leukemia reaction in patients with CML in relapse after bone marrow transplantation.

Methods: Eleven patients with relapsed CML after allogeneic bone marrow transplantation were treated with interferon alfa-2b and infusions of mononuclear cells. The patients were monitored for toxic effects, 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.

Results: Six of the eight patients with stable CML after relapse had complete remissions according to molecular genetic criteria, since no cells with bcr/abl messenger RNA transcripts were detected (the method can identify 1 leukemic cell among 1 million normal cells). The three patients with accelerated CML after relapse did not enter remission. Myelosuppression was prominent in eight patients. Grade I acute graft-versus-host disease (GVHD) occurred in six patients, and grade III acute GVHD occurred in three. Limited chronic GVHD developed in five patients.

Conclusions: The induction of a graft-versus-leukemia reaction with interferon alfa-2b and infusions of donor mononuclear cells in patients with CML in relapse after bone marrow transplantation is an effective antileukemic therapy that may offer an alternative to a second marrow transplantation.