Clonal Dynamics and clinical implications of Post Remission Clonal Hematopoiesis in Acute Myeloid Leukemia (AML)
While clonal hematopoiesis (CH) can precede the development of acute myeloid leukemia (AML) it can also persist after achieving remission. Long term clonal dynamics and clinical implications of persistent CH are not well understood. Here, we studied the prevalence, dynamics and clinical implications of post remission CH in 164 AML patients who attained complete remission after induction chemotherapies. Post remission CH was identified in 79 (49% patients. Post remission CH persisted long term in 91% of the trackable patients despite treatment with various types of consolidation and maintenance therapies. Post remission CH was eradicated in 20 out of 21 (95% patients who underwent allogeneic stem cell transplant. While patients with post remission CH as a group had comparable hematopoiesis with those without it, patients with persistent TET2 mutations showed significant neutropenia long term. Post remission CH had little impact on relapse risk, non relapse mortality, and incidence of atherosclerotic cardiovascular disease, although the clinical impact of post CR CH was heterogeneous among different mutations. These data suggest that while residual clonal hematopoietic stem cells (HSCs) are generally resistant to consolidation and maintenance therapies, they retain the ability to maintain normal hematopoiesis and have little impact on clinical outcomes, although larger study is needed to dissect the gene specific heterogeneity.
Blood