Stability of leukemia‐associated aberrant immunophenotypes in patients with acute myeloid leukemia between diagnosis and relapse: Comparison with cytomorphologic, cytogenetic, and molecular genetic findings

Abstract

Background: Multiparameter flow cytometry is increasingly used to monitor minimal residual disease in patients with acute myeloid leukemia to identify leukemic cells by leukemia-associated aberrant immunophenotypes (LAIPs). Changes in LAIPs during the course of the disease may be a limitation for this approach.Methods: We analyzed 49 patients at diagnosis and relapse by flow cytometry, cytomorphology, cytogenetics, and molecular genetics.Results: In 37 patients (76%), at least one LAIP detectable at diagnosis was present at relapse; in 12 patients (24%), none of the original LAIPs were present in at least 1% of bone marrow cells. Three groups were identified: no change in LAIPs, partial changes in LAIPs, and complete change in LAIPs. There were significant differences across these groups with regard to changes in cytomorphology (11%, 40%, and 58% of all cases, respectively; P ‫؍‬ 0.007), cytogenetics (15%, 20%, and 25%; not significant), and molecular genetics (18%, 0, and 86%; P ‫؍‬ 0.002).Conclusions: These data indicate that, in a subset of patients with acute myeloid leukemia, the disease is biologically different at relapse; therefore, monitoring of minimal residual disease is difficult to accomplish. In most patients with acute myeloid leukemia, multiparameter flow cytometry may be used to monitor minimal residual disease.

Clinical significance of flowcytometric minimal residual disease detection in pediatric acute myeloid leukemia patients treated according to the DCOG ANLL97/MRC AML12 protocol

“…Voskova et al 21 found at least one stable LAIP in 76% of adult patients with AML. In this study, in only four patients the applied LAIP labelings did not detect the majority of leukemic cells at relapse.…”

Minimal residual disease diagnostics in myeloid malignancies in the post transplant period

“…105 However, in the post transplantation setting the use of multiparameter flow cytometry still has to be validated as changes of the immunophenotype might be more frequent in relapse following SCT than after standard therapy where complete loss of the previous LAIP is seen in B25%. 106 In one case an increase of cells with the AML-specific immunophenotype 2 months from transplantation was an indication for the withdrawal of immunosuppression that was followed by a reduction of aberrant cells. 107 So far, only very few studies 108 addressed the value of MRD by immunophenotyping in AML specifically in the post transplantation period, but it was shown that leukemic blasts can be separated from regenerating blasts by multiparameter flow cytometry after SCT.…”

The kinetics of reduction of minimal residual disease impacts on duration of response and survival of patients with acute myeloid leukemia

“…At least two antibody combinations were selected in each single case to minimize pitfalls owing to 'phenotypic switches' that have been described to be occasionally associated with relapses. 19,20 Asynchronous and cross-lineage antigen expression represented the most frequent observed 'leukemia-associated' phenotypes, with the lack of antigen accounting for the remaining cases. Table 1 reports a list of the observed leukemia-associated phenotypes.…”