Clinical Use of Measurable Residual Disease in Acute Myeloid Leukemia

Abstract

Treatment of acute myeloid leukemia (AML) remains a high-risk venture for the patient suffering from the disease. There is a real risk of succumbing to the treatment rather than the disease, and even so, cure is much less than certain. Since the establishment of complete remission as a prerequisite for cure in the 1960s, a number of years passed before advanced techniques for detecting minute amounts of disease matured sufficiently for clinical implementation. The two main techniques for detection of measurable residual disease (MRD) remain qPCR and multicolor flow cytometry. When performed in expert laboratories, both these modalities offer treating physicians excellent opportunity to follow the amount of residual disease upon treatment and offer unparalleled prognostication. In some AML and age group subsets, evidence now exist to support the choice of both proceeding to allogeneic transplant and not doing so. In other AML subgroups, MRD has sufficient discriminative power to identify patients likely to benefit from allogeneic transplant and patients likely not to. After treatment or transplantation, follow-up by molecular techniques can, with high certainty, predict relapse months before bone marrow function deterioration. On the other hand, options upon so-called molecular relapse are less well tested but recent evidence supports the use of azacitidine both in transplanted patients and patients consolidated with chemotherapy. In conclusion, MRD testing during treatment is a superb prognosticator and a major tool when choosing whether a patient should be transplanted or not. The exact use of MRD testing after treatment is less well defined but evidence is mounting for the instigation of treatment upon rising MRD levels (pre-emptive treatment) before morphologically detectable relapse.

Keywords: Acute myeloid leukemia, AML; Allogeneic stem cell transplantation; Complete remission; Measurable residual disease, MRD; Multicolor flow cytometry; Pre-emptive treatment; Surveillance; qPCR.