Abstract
The detection of measurable residual disease (MRD) has become a key investigation that plays a role in the prognostication and management of several hematologic malignancies. Acute myeloid leukemia (AML) is the most common acute leukemia in adults and the role of MRD in AML is still emerging. Prognostic markers are complex, largely based upon genetic and cytogenetic aberrations. MRD is now being incorporated into prognostic models and is a powerful predictor of relapse. While PCR-based MRD methods are sensitive and specific, many patients do not have an identifiable molecular marker. Immunophenotypic MRD methods using multiparametric flow cytometry (MFC) are widely applicable, and are based on the identification of surface marker combinations that are present on leukemic cells but not normal hematopoietic cells. Current techniques include a “different from normal” and/or a “leukemia-associated immunophenotype” approach. Limitations of MFC-based MRD analyses include the lack of standardization, the reliance on a high-quality marrow aspirate, and variable sensitivity. Emerging techniques that look to improve the detection of leukemic cells use dimensional reduction analysis, incorporating more leukemia specific markers and identifying leukemic stem cells. This review will discuss current methods together with new and emerging techniques to determine the role of MFC MRD analysis.
Highlights
Acute myeloid leukemia (AML) is a hematologic malignancy characterized by more than 20% blasts in the bone marrow and often with recurring genetic abnormalities
In acute lymphoblastic leukemia (ALL), those who are measurable residual disease (MRD) negative complete high-dose chemotherapy alone, whereas those who have high levels (≥1%) MRD at the end of induction or persistent low level MRD have their treatment intensified and are usually recommended to proceed to allogeneic stem cell transplant (alloSCT) if a donor is available [11]
AML is a highly heterogenous malignancy and prognosis has been based around patient and disease factors, with a major emphasis on recurring genetic abnormalities
Summary
Acute myeloid leukemia (AML) is a hematologic malignancy characterized by more than 20% blasts in the bone marrow and often with recurring genetic abnormalities. QPCR methodologies are based upon the detection of the aberrant mutation in leukemic cells as compared to a housekeeper gene, and are sensitive down to frequencies of 1 × 106–7, this varies significantly depending on the genetic target [1]. While this is highly sensitive, only 60% of younger patients, and fewer older patients, have an identifiable PCR target. Immunophenotyping by MFC to assess MRD is applicable to most patients and is based on the identification of surface marker combinations that are present on leukemic cells but not normal hematopoietic stem cells [12]. This review will discuss the use of MFC in the diagnosis of AML; the role of, and evidence for, MRD in AML; and in particular the use of MFC in MRD in AML; and the new and emerging methods for assessing MRD by MFC
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