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

Abstract

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. We report on the measurement of minimal residual disease (MRD), by multicolour flow-cytometry in one centralized laboratory, in 142 children with newly diagnosed AML enrolled in the Associazione Italiana di EmatoOncologia Pediatrica-AML 2002/01 trial. At the end of the first induction course, MRD was <0·1% in 69, 0·1-1% in 16 and >1% in 51 patients. The 8-year disease-free survival (DFS) of 125 children in morphological complete remission and with MRD <0·1%, 0·1-1% and ≥1% was 73·1 ± 5·6%, 37·8 ± 12·1% and 34·1 ± 8·8%, respectively (P < 0·01). MRD was also available after the second induction course in 92/142 patients. MRD was ≥0·1% at the end of the first induction course in 36 patients; 13 reached an MRD <0·1% after the second one and their DFS was 45·4 ± 16·7% vs. 22·8 ± 8·9% in patients with persisting MRD ≥0·1% (P = 0·037). Multivariate analysis demonstrated that MRD ≥0·1% after first induction course was, together with a monosomal karyotype, an independent adverse prognostic factor for DFS. Our results show that MRD detected by flow-cytometry after induction therapy predicts outcome in patients with childhood AML and can help stratifying post-remission treatment.

Prognostic impact of t(16;21)(p11;q22) and t(16;21)(q24;q22) in pediatric AML: a retrospective study by the I-BFM Study Group

“…Currently, early response to therapy is increasingly used for risk-group stratification of therapy in AML. 3,26,27 The detection of MRD through flow cytometry can provide a more accurate measure of therapy response; however, the additional benefit of MRD measurement is inconsistent between AML subtypes and studies and depends on the sensitivity of the applied technique. 3,[28][29][30] In our cohort, MRD data were reported in about one-half of the t(16;21) rearranged cases.…”

Leukemic stem cells: identification and clinical application

“…Assessment of the frequency of remaining leukemic cells present during and after therapy (measurable/minimal residual disease, MRD) is increasingly used as an early read-out of therapy efficacy [6,41]. MRD frequency measurement has been shown to have independent prognostic impact across different cytogenetic and molecular subgroups [42][43][44][45], and is currently used to refine risk group classifications after induction therapy.…”

Highly sensitive chimerism detection in blood is associated with increased risk of relapse after allogeneic hematopoietic cell transplantation in childhood leukemia

“…In AML, MRD is most frequently monitored by flow cytometry with two to three logs lower sensitivities than in ALL . More sensitive PCR‐based analysis can be used in only 50% of children with AML, and with the risk of loss of markers or persistence of fusion transcripts, the interpretation is complicated . Furthermore, MRD is primarily analyzed on bone marrow samples, which limits the frequency of measurements in children.…”