Immunotherapy for acute leukemia

(allo-HCT) can be curative for patients with acute leukemia [1]. The anti-leukemia activity relies on the graft-versus-leukemia (GVL) effects that are elicited after allo-HCT, suggesting that anti-tumor immunity may be responsible for eradicating leukemia and preventing subsequent relapse. However, allo-HCT is associated with significant morbidity and mortality resulting from toxicity of dose-intensive conditioning regimens and graft-versus-host disease (GVHD), limiting allo-HCT to younger and medically fit patients. Over the last two decades, non-myeloablative conditioning regimens have been developed to reduce toxicity and allow the use of allo-HCT in older patients [2]. These regimens are designed to provide sufficient immune suppression just to allow donor cell engraftment and induction of GVL effects as the primary therapy. Despite the more frequent use of non-myeloablative allo-HCT in older patients, GVHD still remains a major challenge. Several retrospective studies have demonstrated that both acute and chronic GVHD are associated with a decreased incidence of relapses [3, 4]. However, effects of chronic GVHD on relapse are difficult to separate from acute GVHD effects, because most cases of chronic GVHD occur within the first year after transplant, at the time when acute GVHD is still active. Also, since majority leukemia relapses occur within the first year after allo-HCT, there is possibility of little net-additive chronic GVHD anti-leukemic benefit when it comes to affecting late (>12 months) relapses. In a recent study, we evaluated the effects of chronic GVHD on late relapse in 7,489 allo-HCT recipients who were alive one year after HCT [5]. The protective effect of chronic GVHD on late relapse was present only in patients with chronic myeloid leukemia (CML) and was not seen in patients with acute leukemia. Although providing protection from late relapse in patients with CML, chronic GVHD was associated with higher risk of treatment-related mortality and inferior overall survival for all diseases. These results suggest that development of more assertive strategies for chronic GVHD therapy and prevention should be justified to decrease treatment related mortality after allo-HCT. Within the first year after allo-HCT both treatment related mortality and leukemic relapse can be as high as 30-40% in high risk patients [6]. In view of these Editorial results, the question arise is whether we can mimic the GVL effects of donor cells by enhancing the antitumor effects of the patients' immune system and avoiding allo-HCT and its associated complications. The answer to this question is " not yet. " The prospect is …