Relapsed acute myeloid leukemia: Why is there no standard of care?

Abstract

Relapse after achieving a prior response remains one of the most important obstacles to improving the outcome of patients with acute myeloid leukemia (AML). Although overall, the majority of patients with disease relapse do poorly, this is by no means uniform and a number of predictors of outcome have been identified. Previously, most trials of investigational agents in the setting of disease relapse in AML have accrued a wide range of patients with widely different patient and disease characteristics. With increased understanding of the biology of the neoplastic change in AML, and better identification of disease subsets based on their molecular characterization, target-specific novel agents are being developed that will hopefully lead to better strategies, not only for treating relapsed disease, but also for the initial induction treatment.

Dendritic cell vaccination as postremission treatment to prevent or delay relapse in acute myeloid leukemia

“…One of the major reasons for this is that a majority of patients relapse even after complete remission (CR) is achieved with standard chemotherapy. 3 Relapse is usually caused by the persistence of a small population of residual leukemic cells, a condition designated as minimal residual disease (MRD). 4 Allogeneic hematopoietic stem-cell transplantation (allo-HSCT), the best established postremission treatment to eradicate MRD, decrease the risk of relapse, and increase survival after chemotherapy, is still beset by substantial morbidity and mortality.…”

Considerations and challenges for patients with refractory and relapsed acute myeloid leukaemia

“…Multiple inter-related factors, including age, cytogenetics, immunophenotypic changes, and (in the case of relapsed AML) duration of first CR, have been shown to affect treatment outcomes for patients with rrAML [15][16][17][18]. Variability in these characteristics among patient populations in treatment studies may be one reason why clinical trials thus far have failed to identify a single preferred regimen or standard of care [13].…”

“…Overall, patients with rrAML have a poor prognosis and few treatment options, as there currently is no standard of care [8,13]. Challenges in treating patients with rrAML include accurately assessing the disease prognosis and likelihood of achieving CR, selecting the salvage therapy that is most likely to succeed and that can be tolerated, and identifying patients for whom haematopoietic cell transplantation (HCT) is a viable option [14].…”

Multi-color flow cytometric immunophenotyping for detection of minimal residual disease in AML: past, present and future

“…2 Currently, pre-treatment factors such as age, cytogenetic risk score and mutational profile are used for risk stratification and clinical decision making. 1,5,6 However, the individual patient's response to therapy is also an important prognostic factor that should ideally be integrated into the risk stratification to help identify candidates who may benefit from alternative therapeutic agents or hematopoietic SCT.…”

“…1 Current treatment regimens achieve CR in the majority of adult patients; however, approximately 65% of patients develop relapsed disease. 2,3 Thus, there is a need to effectively identify which patients are at most risk for impending relapse. Low levels of leukemic cells, termed minimal residual disease (MRD), have been shown to correlate with an increased risk of relapse and shortened survival believed to be a major cause of relapse.…”