Mutation burden in the peripheral blood of AML and MDS patients

Assessment of therapeutic response in patients with Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS) typically relies on the morphologic quantification of Bone Marrow (BM) blasts. However, this method is limited by sample error and challenging drug toxicities.

In a Letter to the Editor of Blood, Eric J. Duncavage and colleagues from the Washington University School of Medicine, St. Louis, USA, discuss their study which aimed to determine whether sequencing of Peripheral Blood (PB) samples is a feasible approach for determining clonal architecture and whether it might provide a less invasive measure of response of therapy in AML and MDS patients.

To do this, the authors quantified the mutation burden in the PB and compared it to the BM samples in twenty-seven patients (AML, n = 22; MDS, n = 5; median age = 73 years) with at least two somatic mutations in the BM treated with a 10-day course of decitabine (NCT01687400) at Washington University School of Medicine.

The key results of the study were:

• Similar subclonal architecture and copy number variation were observed in patient samples from the PB and BM
• Rate of clone mutational clearance during decitabine treatment correlated between the PB and BM; R² = 0.69, P < 0.001

In summary, targeted PB mutation analysis recapitulates the genomic events observed in the BM blasts of AML and MDS patients. Additionally, PB mutation analysis quantifies the clearance of mutations as a distinct end point which is not influenced by drug toxicity.

The authors concluded by suggesting that “PB mutation analysis may provide a less invasive alternative for monitoring response to treatment” in AML and MDS patients which is not subject with the issues observed with BM monitoring.