Prognostic factors associated with therapeutic response

Response to therapy/minimal residual disease (MRD): Early response to therapy, generally measured after the first course of induction therapy, is predictive of outcome and can be assessed by standard morphological examination of bone marrow,[49,66] cytogenetic analysis, fluorescence in situ hybridization, or more sophisticated techniques to identify MRD (e.g., multiparameter flow cytometry, quantitative RT-PCR).[67-69] Multiple groups have shown that the level of MRD after one course of induction therapy is an independent predictor of prognosis.[67-72]Molecular approaches to assessing MRD in AML: Molecular approaches (e.g., using quantitative RT-PCR) have been challenging to apply because of the genomic heterogeneity of pediatric AML and the instability of some genomic alterations. Results have shown the following:Flow cytometric methods: Flow cytometry has been used for MRD detection and can detect leukemic blasts based on the expression of aberrant surface antigens that differ from the pattern observed in normal progenitors.

Response to therapy/minimal residual disease (MRD): Early response to therapy, generally measured after the first course of induction therapy, is predictive of outcome and can be assessed by standard morphological examination of bone marrow,[49,66] cytogenetic analysis, fluorescence in situ hybridization, or more sophisticated techniques to identify MRD (e.g., multiparameter flow cytometry, quantitative RT-PCR).[67-69] Multiple groups have shown that the level of MRD after one course of induction therapy is an independent predictor of prognosis.[67-72]Molecular approaches to assessing MRD in AML: Molecular approaches (e.g., using quantitative RT-PCR) have been challenging to apply because of the genomic heterogeneity of pediatric AML and the instability of some genomic alterations. Results have shown the following:Flow cytometric methods: Flow cytometry has been used for MRD detection and can detect leukemic blasts based on the expression of aberrant surface antigens that differ from the pattern observed in normal progenitors.

Quantitative RT-PCR detection of RUNX1::RUNX1T1 fusion transcripts can effectively predict higher risk of relapse for patients in clinical remission.[73-75]

Response to therapy/minimal residual disease (MRD): Early response to therapy, generally measured after the first course of induction therapy, is predictive of outcome and can be assessed by standard morphological examination of bone marrow,[49,66] cytogenetic analysis, fluorescence in situ hybridization, or more sophisticated techniques to identify MRD (e.g., multiparameter flow cytometry, quantitative RT-PCR).[67-69] Multiple groups have shown that the level of MRD after one course of induction therapy is an independent predictor of prognosis.[67-72]Molecular approaches to assessing MRD in AML: Molecular approaches (e.g., using quantitative RT-PCR) have been challenging to apply because of the genomic heterogeneity of pediatric AML and the instability of some genomic alterations. Results have shown the following:Flow cytometric methods: Flow cytometry has been used for MRD detection and can detect leukemic blasts based on the expression of aberrant surface antigens that differ from the pattern observed in normal progenitors.

Other molecular alterations such as NPM1 variants [76] and CBFB::MYH11 fusion transcripts [77] have also been successfully employed as leukemia-specific molecular markers in MRD assays. For these alterations, the level of MRD has shown prognostic significance.

Response to therapy/minimal residual disease (MRD): Early response to therapy, generally measured after the first course of induction therapy, is predictive of outcome and can be assessed by standard morphological examination of bone marrow,[49,66] cytogenetic analysis, fluorescence in situ hybridization, or more sophisticated techniques to identify MRD (e.g., multiparameter flow cytometry, quantitative RT-PCR).[67-69] Multiple groups have shown that the level of MRD after one course of induction therapy is an independent predictor of prognosis.[67-72]Molecular approaches to assessing MRD in AML: Molecular approaches (e.g., using quantitative RT-PCR) have been challenging to apply because of the genomic heterogeneity of pediatric AML and the instability of some genomic alterations. Results have shown the following:Flow cytometric methods: Flow cytometry has been used for MRD detection and can detect leukemic blasts based on the expression of aberrant surface antigens that differ from the pattern observed in normal progenitors.

The presence of FLT3 ITD has been shown to be discordant between diagnosis and relapse, although when its presence persists (usually associated with a high-allelic ratio at diagnosis), it can be useful in detecting residual leukemia.[78]

Response to therapy/minimal residual disease (MRD): Early response to therapy, generally measured after the first course of induction therapy, is predictive of outcome and can be assessed by standard morphological examination of bone marrow,[49,66] cytogenetic analysis, fluorescence in situ hybridization, or more sophisticated techniques to identify MRD (e.g., multiparameter flow cytometry, quantitative RT-PCR).[67-69] Multiple groups have shown that the level of MRD after one course of induction therapy is an independent predictor of prognosis.[67-72]Molecular approaches to assessing MRD in AML: Molecular approaches (e.g., using quantitative RT-PCR) have been challenging to apply because of the genomic heterogeneity of pediatric AML and the instability of some genomic alterations. Results have shown the following:Flow cytometric methods: Flow cytometry has been used for MRD detection and can detect leukemic blasts based on the expression of aberrant surface antigens that differ from the pattern observed in normal progenitors.

In a COG analysis (AAML0531 [NCT00372593]) of 784 patients, the following results were reported:[72]

Response to therapy/minimal residual disease (MRD): Early response to therapy, generally measured after the first course of induction therapy, is predictive of outcome and can be assessed by standard morphological examination of bone marrow,[49,66] cytogenetic analysis, fluorescence in situ hybridization, or more sophisticated techniques to identify MRD (e.g., multiparameter flow cytometry, quantitative RT-PCR).[67-69] Multiple groups have shown that the level of MRD after one course of induction therapy is an independent predictor of prognosis.[67-72]Molecular approaches to assessing MRD in AML: Molecular approaches (e.g., using quantitative RT-PCR) have been challenging to apply because of the genomic heterogeneity of pediatric AML and the instability of some genomic alterations. Results have shown the following:Flow cytometric methods: Flow cytometry has been used for MRD detection and can detect leukemic blasts based on the expression of aberrant surface antigens that differ from the pattern observed in normal progenitors. › In a COG analysis (AAML0531 [NCT00372593]) of 784 patients, the following results were reported:[72]

Sixty-nine percent of patients (n = 544) were MRD negative (defined as <0.02%) in their bone marrow at the end of induction 1 (EOI1).

Response to therapy/minimal residual disease (MRD): Early response to therapy, generally measured after the first course of induction therapy, is predictive of outcome and can be assessed by standard morphological examination of bone marrow,[49,66] cytogenetic analysis, fluorescence in situ hybridization, or more sophisticated techniques to identify MRD (e.g., multiparameter flow cytometry, quantitative RT-PCR).[67-69] Multiple groups have shown that the level of MRD after one course of induction therapy is an independent predictor of prognosis.[67-72]Molecular approaches to assessing MRD in AML: Molecular approaches (e.g., using quantitative RT-PCR) have been challenging to apply because of the genomic heterogeneity of pediatric AML and the instability of some genomic alterations. Results have shown the following:Flow cytometric methods: Flow cytometry has been used for MRD detection and can detect leukemic blasts based on the expression of aberrant surface antigens that differ from the pattern observed in normal progenitors. › In a COG analysis (AAML0531 [NCT00372593]) of 784 patients, the following results were reported:[72]

Those patients had better DFS rates (57%; 95% CI, 53%–61%; P < .001) and OS rates (73%; 95% CI, 69%–76%; P < .001) than patients who were MRD positive (DFS rate, 30%; 95% CI, 25%–36% and OS rate, 48%; 95% CI, 42%–54%).

Response to therapy/minimal residual disease (MRD): Early response to therapy, generally measured after the first course of induction therapy, is predictive of outcome and can be assessed by standard morphological examination of bone marrow,[49,66] cytogenetic analysis, fluorescence in situ hybridization, or more sophisticated techniques to identify MRD (e.g., multiparameter flow cytometry, quantitative RT-PCR).[67-69] Multiple groups have shown that the level of MRD after one course of induction therapy is an independent predictor of prognosis.[67-72]Molecular approaches to assessing MRD in AML: Molecular approaches (e.g., using quantitative RT-PCR) have been challenging to apply because of the genomic heterogeneity of pediatric AML and the instability of some genomic alterations. Results have shown the following:Flow cytometric methods: Flow cytometry has been used for MRD detection and can detect leukemic blasts based on the expression of aberrant surface antigens that differ from the pattern observed in normal progenitors. › In a COG analysis (AAML0531 [NCT00372593]) of 784 patients, the following results were reported:[72]

Additionally, in the 76% of patients who were in morphological remission at EOI1, 20% were MRD positive and had a significantly worse outcome than patients who were MRD negative/morphology negative.

Response to therapy/minimal residual disease (MRD): Early response to therapy, generally measured after the first course of induction therapy, is predictive of outcome and can be assessed by standard morphological examination of bone marrow,[49,66] cytogenetic analysis, fluorescence in situ hybridization, or more sophisticated techniques to identify MRD (e.g., multiparameter flow cytometry, quantitative RT-PCR).[67-69] Multiple groups have shown that the level of MRD after one course of induction therapy is an independent predictor of prognosis.[67-72]Molecular approaches to assessing MRD in AML: Molecular approaches (e.g., using quantitative RT-PCR) have been challenging to apply because of the genomic heterogeneity of pediatric AML and the instability of some genomic alterations. Results have shown the following:Flow cytometric methods: Flow cytometry has been used for MRD detection and can detect leukemic blasts based on the expression of aberrant surface antigens that differ from the pattern observed in normal progenitors. › In a COG analysis (AAML0531 [NCT00372593]) of 784 patients, the following results were reported:[72]

In the 24% of patients who were not in morphological remission, 36% were actually MRD negative and had significantly better outcomes than patients who were MRD positive/morphology positive.

Response to therapy/minimal residual disease (MRD): Early response to therapy, generally measured after the first course of induction therapy, is predictive of outcome and can be assessed by standard morphological examination of bone marrow,[49,66] cytogenetic analysis, fluorescence in situ hybridization, or more sophisticated techniques to identify MRD (e.g., multiparameter flow cytometry, quantitative RT-PCR).[67-69] Multiple groups have shown that the level of MRD after one course of induction therapy is an independent predictor of prognosis.[67-72]Molecular approaches to assessing MRD in AML: Molecular approaches (e.g., using quantitative RT-PCR) have been challenging to apply because of the genomic heterogeneity of pediatric AML and the instability of some genomic alterations. Results have shown the following:Flow cytometric methods: Flow cytometry has been used for MRD detection and can detect leukemic blasts based on the expression of aberrant surface antigens that differ from the pattern observed in normal progenitors. › In a COG analysis (AAML0531 [NCT00372593]) of 784 patients, the following results were reported:[72]

This was also true in patients with marrow blast percentages in excess of 15%, 27% of whom had MRD-negative bone marrow and significantly better outcomes.

Response to therapy/minimal residual disease (MRD): Early response to therapy, generally measured after the first course of induction therapy, is predictive of outcome and can be assessed by standard morphological examination of bone marrow,[49,66] cytogenetic analysis, fluorescence in situ hybridization, or more sophisticated techniques to identify MRD (e.g., multiparameter flow cytometry, quantitative RT-PCR).[67-69] Multiple groups have shown that the level of MRD after one course of induction therapy is an independent predictor of prognosis.[67-72]Molecular approaches to assessing MRD in AML: Molecular approaches (e.g., using quantitative RT-PCR) have been challenging to apply because of the genomic heterogeneity of pediatric AML and the instability of some genomic alterations. Results have shown the following:Flow cytometric methods: Flow cytometry has been used for MRD detection and can detect leukemic blasts based on the expression of aberrant surface antigens that differ from the pattern observed in normal progenitors.

A CCG study of 252 pediatric patients with AML in morphological remission demonstrated the following:[79]

Response to therapy/minimal residual disease (MRD): Early response to therapy, generally measured after the first course of induction therapy, is predictive of outcome and can be assessed by standard morphological examination of bone marrow,[49,66] cytogenetic analysis, fluorescence in situ hybridization, or more sophisticated techniques to identify MRD (e.g., multiparameter flow cytometry, quantitative RT-PCR).[67-69] Multiple groups have shown that the level of MRD after one course of induction therapy is an independent predictor of prognosis.[67-72]Molecular approaches to assessing MRD in AML: Molecular approaches (e.g., using quantitative RT-PCR) have been challenging to apply because of the genomic heterogeneity of pediatric AML and the instability of some genomic alterations. Results have shown the following:Flow cytometric methods: Flow cytometry has been used for MRD detection and can detect leukemic blasts based on the expression of aberrant surface antigens that differ from the pattern observed in normal progenitors. › A CCG study of 252 pediatric patients with AML in morphological remission demonstrated the following:[79]

MRD, assessed by flow cytometry, was the strongest prognostic factor predicting outcome in a multivariate analysis.

Response to therapy/minimal residual disease (MRD): Early response to therapy, generally measured after the first course of induction therapy, is predictive of outcome and can be assessed by standard morphological examination of bone marrow,[49,66] cytogenetic analysis, fluorescence in situ hybridization, or more sophisticated techniques to identify MRD (e.g., multiparameter flow cytometry, quantitative RT-PCR).[67-69] Multiple groups have shown that the level of MRD after one course of induction therapy is an independent predictor of prognosis.[67-72]Molecular approaches to assessing MRD in AML: Molecular approaches (e.g., using quantitative RT-PCR) have been challenging to apply because of the genomic heterogeneity of pediatric AML and the instability of some genomic alterations. Results have shown the following:Flow cytometric methods: Flow cytometry has been used for MRD detection and can detect leukemic blasts based on the expression of aberrant surface antigens that differ from the pattern observed in normal progenitors.

Other reports have confirmed both the utility of flow cytometric methods for MRD detection in the pediatric AML setting and the prognostic significance of MRD at various time points after treatment initiation.[67,68,70]