Changing fate by personalizing treatment for a high-risk blood cancer

2020

Challenge

Every year 20,000 Americans develop a highly fatal blood cancer called acute myeloid leukemia (AML). Unfortunately, even for those who achieve a clinical remission after chemotherapy and a bone marrow transplant, the cancer still often comes back. In some of these patients, it is possible to detect very low-level traces of residual leukemia, which are associated with a higher likelihood of subsequent relapse. However, it was not known if this ‘measurable residual disease’ in AML was just an early sign of an inevitable relapse or if it could be treated to prevent the cancer from recurring.

Advance

IRP researchers led by investigator Christopher S. Hourigan M.D., D.Phil., looked at pre-transplant blood samples taken from adults with AML participating in the NIH-funded Blood and Marrow Transplant Clinical Trials Network study. This study treated AML patients already in clinical remission with either standard high-dose preparative therapy before their bone marrow transplants or a lower-intensity approach designed to reduce treatment-related toxicity. Using cutting-edge, highly sensitive genomic diagnostics, the IRP researchers confirmed a clear benefit of higher-dose therapy for those in clinical remission who showed signs of residual disease.

Impact

This work demonstrated that conventional clinical methods for determining the success of AML treatment are not sensitive enough to identify those who would benefit from additional therapy. The findings allow for optimal therapy selection and personalized treatment in preparation for bone marrow transplant in AML patients and also point towards the potential for novel clinical trials that focus on those with the highest risk of relapse after receiving a transplant.

Publications

Hourigan CS, Dillon LW, Gui G, Logan BR, Fei M, Ghannam J, Li Y, Licon A, Alyea EP, Bashey A, Deeg HJ, Devine SM, Fernandez HF, Giralt S, Hamadani M, Howard A, Maziarz RT, Porter DL, Scott BL, Warlick ED, Pasquini MC, Horwitz ME. (2020). Impact of conditioning intensity of allogeneic transplantation for acute myeloid leukemia with genomic evidence of residual disease. J. Clin. Oncol. Apr 20;38(12):1273-1283.

Hourigan CS, Dillon LW, Logan BR, Fei M, Ghannam J, Gui G, Li Y, Licon A, Alyea EP, Bashey A, Deeg HJ, Devine SM, Fernandez HF, Giralt S, Hamadani M, Howard A, Maziarz RT, Porter DL, Scott BL, Warlick ED, Pasquini MC, Horwitz ME. (2019). Impact of conditioning intensity of allogeneic transplantation for acute myeloid leukemia with genomic evidence of residual disease. European Hematology Association Annual Congress, Amsterdam. Presidential Plenary Symposium, June 14th, 2019.