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

Abstract

Analysis of minimal residual disease (MRD) in childhood acute myeloid leukemia (AML) may predict for clinical outcome. MRD levels were assessed by flowcytometric immunophenotyping in 94 children with AML enrolled into a single trial (United Kingdom Medical Research Council AML12 and similar Dutch Childhood Oncology Group ANLL97). An aberrant immunophenotype could be detected in 94% of patients. MRD levels after the first course of chemotherapy predicted for clinical outcome: 3-year relapse-free survival was 85% ± 8% (s.e.) for MRD-negative patients (MRDo0.1%), 64%±10% for MRDlow-positive patients (0.1%pMRDo0.5%) and only 14±9% for MRD-high-positive patients (MRDX0.5%; Po0.001), whereas overall survival was 95% ± 5%, 70% ± 10% and 40% ± 13%, respectively, (Po0.001). Multivariate analysis allowing for age, karyotype, FLT3-internal tandem duplications and white blood cell count at diagnosis showed that MRD after the first course of chemotherapy was an independent prognostic factor. Although comparison of paired diagnosis-relapse samples (n ¼ 23) showed immunophenotypic shifts in 91% of cases, this did not hamper MRD analysis. In conclusion, flowcytometric MRD detection is possible in children with AML. The level of MRD after the first course of chemotherapy provides prognostic information that may be used to guide therapy.

Outcome after failure of allogeneic hematopoietic stem cell transplantation in children with acute leukemia: a study by the société Francophone de greffe de moelle et de thérapie cellulaire (SFGM-TC)

“…Specific genetic predictors and MRD strongly correlate with the treatment outcome [19][20][21][22] and may guide risk-stratified therapeutic decisions. The development of highly sensitive MRD techniques standardized for all patients, genetic profiling and identification of other predicting factors are required for better-individualized treatments.…”

Diagnosis and management of acute myeloid leukemia in children and adolescents: recommendations from an international expert panel

“…Whereas some groups failed to show an independent prognostic impact, other groups have used the technique for treatment intensification. 10,62,63 Current technologic advances, such as Ն 6-color flow cytometry, may overcome any limitations. However, method standardization and quality control are essential.…”

Improved outcome of children transplanted for high-risk leukemia by using a new strategy of cyclosporine-based GVHD prophylaxis

“…The MRD positivity was defined as ⩾ 10 − 3 . [22][23][24][25] Statistical analysis All statistical analyses were performed using SPSS for Windows (version 11.0; SPSS, Chicago, IL, USA). Pearson's χ 2 tests were used to compare possible differences in qualitative variables between groups of patients.…”

“…Allele-specific oligonucleotide-PCR was performed and interpreted as described in up-to-date EuroMRD guidelines. 22 Multiparameter flow cytometry was performed on fresh cells after erythrocyte lysis using staining with Ab panels, as described previously in ALL. 23 At diagnosis, leukemia-associated immunophenotypes were determined on 10 000 to 15 000 nucleated cells.…”