Measurable residual disease in patients undergoing allogeneic transplant for acute myeloid leukemia

Allogeneic hematopoietic cell transplant (alloHCT) is a well-established and effective anti-cancer cellular immunotherapy, widely used for maintenance of remission in patients with acute myeloid leukemia (AML). AlloHCT is broadly recommended as standard consolidative therapy for patients with AML, except for those with the lowest risk of relapse or who are unable or unwilling to tolerate a transplant. On average, alloHCT lowers the risk of relapse for those with AML but many patients still experience relapse despite entering alloHCT in remission. It has been known for over forty years that “complete” remission defined by cytomorphology and count recovery represents a range of residual potential disease burdens, which explains the disparate clinical outcomes observed in patients in this response state after treatment [[1], [2], [3]]. High sensitivity testing of patients with AML in remission can identify, in some patients, evidence of disease persistence (“measurable residual disease”, MRD) [[4], [5], [6]]. Patients with AML in remission testing positive for MRD have a higher risk of relapse and death [7,8], including when measured in remission immediately prior to alloHCT [[9], [10], [11], [12], [13]].

The disease heterogeneity and diverse genetic aetiology of AML, the often-complex clonal architecture, and lack of test availability and harmonization for this set of rare diseases are among the factors that have limited the clinical impact of AML MRD testing including in those undergoing alloHCT. There are however several key areas where peri-transplant AML MRD testing may have clinical utility (Table 1).

This article will review the methods currently recommended by an international expert consensus panel for clinical MRD testing in AML, discuss advances in the use of molecular techniques in particular next-generation sequencing for specific common molecular AML subsets, describe the evidence for testing MRD after transplantation, the role of conditioning intensification and maintenance therapy in patients with detectable MRD, and propose a research agenda including a description of ongoing and forthcoming efforts to generate high quality evidence for AML MRD testing in patients undergoing alloHCT.

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