THE GRAFT-VERSUS-LEUKEMIA (GVL) EFFECT AFTER ALLOGENEIC BONE-MARROW TRANSPLANTATION FOR CHRONIC MYELOGENOUS LEUKEMIA (CML)

Immune mechanisms superimposed to the myeloablative conditioning regim ens exert an additional powerful effect in eradicating leukemia and in achieving immunological control of minimal residual disease. The impa ct of GVHD-independent GVL has been evaluated to be absent, or near ab sent, in ALL, about 30% in AML and about 40% in CML. While until littl e time ago most of the evidence in favor of an immune antileukemia mec hanism exerted by allo BMT in CML was indirect, based on the lack of G VL, there is now solid evidence of a positive type, based on the antil eukemia effect of donor lymphocyte infusions in patients having relaps ed after transplant. There are three lines of indirect clinical eviden ce for GVL in CML: they include the classical linkage between GVHD and reduced relapse rate, increased relapse rate after identical twin all ografts, and increased relapse risk after effective GVHD prophylaxis, with T lymphocyte depletion in the foreground. The eradicating effects of donor lymphocyte infusions in relapsed patients are the ultimate d emonstration that allogeneic immune competent cells are capable of rec ognizing and destroying the Ph-positive clone. However the frequency o f irreversible aplasia indicates that donor lymphocytes act in the sam e way on residual host hematopoiesis, so that a second graft, without repeat conditioning, should be programmed for such cases.