Updates in immunotherapy for acute myeloid leukemia

The standard treatment and outcomes for adult patients with acute myeloid leukemia (AML) has not changed significantly in the past 40 years and most patients still die from their disease. The standard regimens currently used to induce remission involve high dose induction chemotherapy with cytarabine and an anthracycline. After remission is obtained, this is followed by consolidation chemotherapy to destroy residual leukemic cells. Although obtaining remission is common, the risk of relapse remains high for multifactorial reasons. AML stem cells are thought to be chemotherapy resistant and heterogeneous enough to respond to different selection pressures from chemotherapeutics (1). Additionally, AML has a multitude of techniques to evade the host immune system: Downregulation of non-self human leukocyte antigen, resist natural killer (NK) cells, decreasing antigenicity, producing their own dendritic cells (DCs) leading to T-cell neutralization, and releasing ligands to block T cell attacks (2). For those at increased risk, the best current curative approach is with an allogeneic hematopoietic stem cell transplant (aHSCT). Those who are medically fit to tolerate an aHSCT then have a natural immunotherapy at their defense: graft-versus-leukemic (GVL) effect, where donor NK and T cells are able to destroy both leukemic and leukemic stem cells. Unfortunately, relapse after aHSCT occurs, and the treatment has high morbidity and mortality rates due to increased infection risk, graft-versus-host disease, and additional cancers. A method of utilizing immunotherapy to destroy leukemic cells without the morbidity of a stem cell transplant has garnered much interest over the past several decades. The antitumor effects of immunotherapy have also been recognized in methods other than aHSCT. For example, although the primary mechanism of action for anthracyclines is cytotoxicity, they have shown to stimulate lymphocytes and in animal models success of therapy correlates with the functional status of the immune system (3,4). A search for further methods using the strategies noted above to produce a prolonged remission state with minimal toxicity and risk factors is currently underway