While considerable therapeutic advances using targeted therapies have been made for many malignancies, the most common treatment for acute myeloid leukemia (AML) has not changed in nearly 40 years. Although the majority of patients treated with chemotherapy will achieve an initial remission, subsequent treatment with either further chemotherapy or allogeneic stem cell transplantation (SCT) is effective at preventing leukemic relapse in only approximately half of these individuals. The outlook is often especially suboptimal for those diagnosed with AML but not eligible for this intensive therapy due to advanced age or medical co-morbidity. Despite the lack of progress with conventional treatments, recent advances in the scientific understanding of the genetic diversity of AML, new developments in immunotherapy and the powerful graft-versus-leukemia effect already observed after SCT all offer hope that AML is potentially susceptible to control by the immune system in the non-SCT setting.
Dr. Hourigan’s research focuses on three complementary approaches that are united by an overriding theme of performing translational human immunology research in order to find ways to detect, prevent and treat AML relapse. These efforts are strengthened by collaborations with the NIH’s Center for Human Immunology and Inflammation (CHI), NHLBI core facility expertise in flow cytometry and genomics, and with a variety of clinical colleagues from leukemia centers across the country.
The Myeloid Malignancies Section was established with the mandate to investigate the “detection, prevention and treatment of AML relapse, in particular using non-transplantation immunotherapy”. The first research goal of Dr. Hourigan’s lab is to develop tools for the high sensitivity detection of residual AML after treatment that could help predict patients who may be at risk of relapse and whom may benefit from additional therapy. Such tools may also be able to quantify the efficacy of therapeutic interventions, particularly those given in remission with the intent of preventing relapse. A second, and related, area of research undertaken by Dr. Hourigan’s lab involves the detection and monitoring of specific leukemia immune responses in patients, particularly before and after immunotherapy. By analyzing the “immune health” of AML patients the team hopes to determine predictive biomarkers of the ability to respond to immunotherapy and to search for immune prognostic markers associated with successful long-term clinical outcomes. Finally, while the first two research efforts are “bedside-to-bench” in nature, the third mission of the section is to translate insights from the laboratory back to the clinic, with several ongoing clinical trials of both high sensitivity diagnostics and immunotherapy currently open for AML patients at the NIH clinical center.
The work carried out by Dr. Hourigan’s laboratory should help bring clinicians one step closer to developing more personalized treatments for AML and will hopefully provide a rational platform for the development of the next generation of immunotherapy.