Multidimensional Flow Cytometry for Detection of Minimal Residual Disease in Acute Myeloid Leukemia

Abstract

The term minimal residual disease (MRD) describes the situation in which, after chemotherapy for acute leukemia (AL), a morphologically normal bone marrow (BM) can still harbor a relevant amount of residual malignant cells. Several techniques are now amenable to investigate MRD, and all together they have designated a new era in which a re-definition of the current criteria of complete remission (CR) is required. Depending upon the measured level of MRD we can distinguish a variety of clinical situations ranging from a potentially cured disease to short-term remission. In the context of this spectrum of conditions there would be room for different therapeutic strategies ranging from no further therapy to pre-emptive therapy to treat early relapses (immunologic and/or molecular relapses). This review will focus on the state of art of MRD detection in acute myeloid leukemia (AML) using multidimensional flow cytometry (MFC), and will cover the laboratory and clinical aspects of this approach.

The Role of Multiparameter Flow Cytometry for Detection of Minimal Residual Disease in Acute Myeloid Leukemia

“…13,[17][18][19]21,22,33,39,40 Drach et al 21 evaluated MRD in 68 patients with AML. In follow-up assessment of BM samples collected consecutively after induction therapy, they observed that only patients in whom a LAP continued to be detected experienced early relapse.…”

2006 Bethesda International Consensus recommendations on the flow cytometric immunophenotypic analysis of hematolymphoid neoplasia: Medical indications

“…Assessment of response to therapy (including “minimal residual disease” testing) and persistence of FCI‐detectable MRD following therapy, which is often an adverse prognostic factor. However, the optimal frequency of such monitoring has not been established (112, 137–163). Documentation of progression or relapse. Diagnosis of additional intercurrent hematolymphoid neoplasm, either treatment‐ related (such as MDS/AML or PTLD) or coincidental (164–170).…”

The use of receiver operating characteristic analysis for detection of minimal residual disease using five‐color multiparameter flow cytometry in acute myeloid leukemia identifies patients with high risk of relapse

“…Patients were classified in three risk groups for cytogenetic abnormalities according to Grimwade et al (22). Favorable risk was defined by the presence of t(15;17) or t(8;21) or inv (16) and poor risk was defined by the presence of either five unrelated abnormalities, monosomy 5 or 7, abnormalities of the long arm of chromosome 5, or inv(3) (q21:q26). Patients who did not meet the criteria for poor or favorable risk were classified as intermediate risk.…”

“…Although studies of MRD detection by MFC in AML are still limited when compared with acute lymphoblastic leukemia (ALL) (11)(12)(13)(14), several reports have been published providing evidence that study of MRD are a useful tool for predicting relapse (8)(9)(10)(15)(16)(17)(18)(19)(20).…”