Prognostic significance of flow-cytometry evaluation of minimal residual disease in children with acute myeloid leukaemia treated according to the AIEOP-AML 2002/01 study protocol

Prognostic significance of flow-cytometry evaluation of minimal residual disease in children with acute myeloid leukaemia treated according to the AIEOP-AML 2002/01 study protocol
In children with acute myeloid leukaemia (AML), assessment of initial treatment response is an essential prognostic factor; methods more sensitive than morphology are still under evaluation. In this study the measurement of minimal residual disease (MRD) was reported by multicolour flow-cytometry (MFC) in one centralized laboratory assessed at the end of each of the 2 courses of induction therapy.
This is a retrospective analysis of 142 children with newly diagnosed AML between May 2003 and May 2011 enrolled in the Associazione Italiana di Emato Oncologia Pediatrica (AIEOP)-AML 2002/01 trial with the aim of evaluating the prognostic role of MFC-MRD. All patients had cytogenetic and molecular characterization at diagnosis and were stratified as either “standard risk” (SR) or “high risk” (HR), according to cytogenetic criteria and response to first induction course.
Bone marrow aspirates were collected after the first induction course in 142 patients; 94 of them were also analyzed after the second induction course.
MRD value ≥0·1% at the end of the first induction course has a relevant power to predict patient outcome. Children with positive MRD after induction remain at higher risk of relapse and have poorer outcomes as compared to those with a negative MRD. Relapse in children with MRD negative disease appeared to be correlated with high risk genetic features.
MFC- MRD can not detect minor subclones of AML which can be cause of relapse.
MFC-MRD has a lower limit of sensitivity of 0.1%.
MRD evaluation can be complemented by presenting features, such as genetic abnormalities or high WBC at diagnosis, with the goals of refining risk stratification and, thus, improving the outcome of children with newly diagnosed AML. This study complements other work done by COG and the BFM showing that end-induction MRD is prognostic in AML.