We studied the effect of donor chimerism level on the outcome of donor lymphocyte infusion (DLI) therapy in 42 patients with persistent or relapsed hematologic malignancies after non-T cell-depleted allogeneic hematopoietic cell transplantation. Seventy-five percent of chronic myelogenous leukemia (CML) and 39% of non-CML patients entered remission after DLI therapy. Remission and survival rates were similar for CML patients irrespective of their pre-DLI donor chimerism levels; however, remission occurred sooner in patients with > or =10% pre-DLI donor chimerism. None of the non-CML patients with <10% pre-DLI donor chimerism and 47% of those with > or =10% pre-DLI donor chimerism attained remission. The 2-year survival rates after DLI were 75% for CML and 17% for non-CML patients. We conclude that a low level of donor marrow chimerism is not an adverse prognostic factor for response to DLI in CML patients, but for non-CML patients it may confer worse outcomes. Better methods to augment the response to DLI for patients with hematologic malignancies other than CML that recur after allogeneic hematopoietic cell transplantation are needed, whereas for relapsed CML patients, combination therapies including imatinib mesylate or other promising antileukemic agents may provide outcomes superior to those with DLI alone.