Measurable residual disease to guide transplant related strategies in acute myeloid leukemia
Measurable residual disease to guide transplant related strategies in acute myeloid leukemia
This thesis of Linde Morsink explores the prognostic significance and therapeutic implications of measurable residual disease (MRD) in adults with acute myeloid leukemia (AML) undergoing allogeneic hematopoietic cell transplantation (alloHCT). Through a series of retrospective studies, it demonstrates that MRD status—particularly as assessed before and shortly after transplantation—is a strong predictor of relapse and survival outcomes. The findings show that adverse cytogenetic features such as monosomal karyotype are associated with higher MRD positivity, but MRD itself is the primary driver of poor prognosis, independent of cytogenetic risk.
The thesis also investigates the role of timing and dynamics of MRD response, revealing that early MRD-negative remissions confer lower relapse risk, and that changes in MRD status around transplantation refine risk assessment beyond static MRD measurements. Conditioning intensity interacts with MRD status, with myeloablative regimens providing survival benefits primarily for MRD-negative patients.
Notably, the work highlights that in older AML patients, MRD may be less predictive of outcome following treatment with decitabine or when using post-transplant cyclophosphamide (PTCy) with abbreviated immune suppression. In these settings, relapse and survival outcomes for MRD-positive patients can approximate those of MRD-negative patients, suggesting that modified immune suppression strategies may mitigate the adverse impact of MRD.
Overall, this thesis advances understanding of how MRD can guide risk stratification and personalize transplant-related treatment decisions in AML, particularly in relation to conditioning intensity, treatment timing, and duration of immunosuppression.