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The presence of measurable (minimal) residual disease (MRD) after induction chemotherapy is a strong and independent prognostic marker of increased risk of relapse and shorter survival in patients with acute myeloid leukemia (AML) and can be used to stratify risk and assess treatment response.1 In two of the latest studies, presented at the 61st American Society of Hematology (ASH) Meeting & Exposition, Orlando, US, in December 2019, MRD was used to predict relapse after autologous hematopoietic stem cell transplantation (allo-HSCT). These studies are summarized below.
To learn more about the use of MRD monitoring in the management of AML, visit the AML Global Portal.
The final results of the AML12 trial of the Spanish Cetlam Group were presented by Jorge Sierra, Hospital Santa Creu Sant Pau, Barcelona, ES. This prospective study was designed to evaluate the feasibility and outcomes of prospective, risk-adapted treatment based on AML genetics at diagnosis and the presence of MRD after consolidation chemotherapy.
A total of 812 adults (Table 1) were enrolled at 15 Spanish academic hospitals. Induction chemotherapy, which was administered to all patients, consisted of idarubicin plus cytarabine. Consolidation treatment was high-dose cytarabine (HDAC), with the number of courses depending on genetic risk: two courses for those with European LeukemiaNet (ELN)-favorable genetics and one for those with ELN-intermediate or -adverse genetics. Any subsequent therapy was allocated based on genetic and MRD risk analysis as follows:
HR, high ratio; LR, low ratio; MRC, Medical Research Council; WBC, white blood cells | |
N= 812 (%) | |
Median age, years (range) | 55 (18–70) |
---|---|
Male | 421 (52) |
Median WBC x109/L (range) | 9.6 (0–530) |
Cytogenetics (MRC) | n= 764 (%) |
Favorable | 81 (11) |
Intermediate | 516 (67) |
Normal karyotype | 378 (73) |
Adverse | 167 (22) |
Mutations in intermediate MRC | |
NPM1+/FLT3-ITD negative | 137 (26) |
NPM1+/FLT3-ITD LR | 35 (7) |
NPM1+/FLT3-ITD HR | 55 (11) |
NPM1-/FLT3-ITD positive | 42 (8) |
CEBPα mut. (biallelic) | 12 (2) |
Triple mut neg./lack of information | 210 (41)/25 (5) |
Based on these results, the investigators concluded that MRD was a good marker to predict relapse after consolidation chemotherapy and that allo-HSCT was feasible in a large proportion of patients in intermediate or adverse risk groups based on genetics and/or MRD positivity. However, they also believe that allo-HSCT during the first CR could be avoided in more than one-third of patients (those with favorable genetics at diagnosis and no MRD), since 5-year survival rates were high after chemotherapy only.
Monitoring MRD after allo-HSCT is highly predictive of relapse and overall survival in AML, according to the results of a study presented by Felicitas Thol, Hannover Medical School, Hannover, DE. Building on previous work, which demonstrated that MRD status before allo-HSCT was predictive of relapse and non-relapse mortality (NRM),4 Thol and coworkers set out to answer the question of whether next-generation sequencing (NGS) from peripheral blood can be used to quantify MRD in AML patients who had undergone allo-HSCT. Samples (primarily peripheral blood) from 138 patients were taken at Day 90 (n= 133) and Day 180 (n= 125) post-transplant, and MRD was assessed by NGS, implementing read families of 42 different genes in order to overcome detection errors.
NGS-based MRD monitoring of peripheral blood after allo-HSCT is feasible and predicts future relapse and survival in AML. It should be performed at Day 90 post-transplant with an extended marker set of non-DTA markers in order to help guide post-transplant care in AML patients.
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