Response kinetics and factors predicting survival in core-binding factor leukemia

Boddu, Prajwal; Gurguis, Christopher I.; Sanford, David; Cortes, Jorge; Akosile, Mary; Ravandi, Farhad; Patel, Keyur P.; Kadia, Tapan M.; Brandt, Mark; Maduike, Rita; Kantarjian, Hagop M.; Borthakur, Gautam

doi:10.1038/s41375-018-0158-1

Cited by 25 publications

(37 citation statements)

References 15 publications

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“…2,66 PCR-based MRD assessment of CBFB-MYH11 and RUNX1-RUNX1T1 transcripts for patients with inv(16) and t(8;21), respectively, has been consistently associated with risk of relapse across several studies. 32,33,[67][68][69][70] In the largest study of core-binding factor AML and MRD, 278 patients [163 with t(8;21) and 115 with inv(16)] were treated. 33 A >3 log reduction in RUNX1-RUNX1T1 in the bone marrow and CBFB-MYH11 copy number >10 in the peripheral blood after induction were the most prognostic measures of MRD for risk of relapse.…”

Section: Polymerase Chain Reaction-based Measurable Residual Disease mentioning

confidence: 99%

How close are we to incorporating measurable residual disease into clinical practice for acute myeloid leukemia?

Short

Ravandi

2019

Haematologica

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Assessment of measurable residual disease, also called “minimal residual disease,” in patients with acute myeloid leukemia in morphological remission provides powerful prognostic information and complements pretreatment factors such as cytogenetics and genomic alterations. Based on data that low levels of persistent or recurrent residual leukemia are consistently associated with an increased risk of relapse and worse long-term outcomes, its routine assessment has been recommended by some experts and consensus guidelines. In addition to providing important prognostic information, the detection of measurable residual disease may also theoretically help to determine the optimal post-remission strategy for an individual patient. However, the full therapeutic implications of measurable residual disease are uncertain and thus controversy exists as to whether it should be routinely incorporated into clinical practice. While some evidence supports the use of allogeneic stem cell transplantation or hypomethylating agents for some subgroups of patients in morphological remission but with detectable residual leukemia, the appropriate use of this information in making clinical decisions remains largely speculative at present. To resolve this pressing clinical issue, several ongoing studies are evaluating measurable residual disease-directed treatments in acute myeloid leukemia and may lead to new, effective strategies for patients in these circumstances. This review examines the common technologies used in clinical practice and in the research setting to detect residual leukemia, the major clinical studies establishing the prognostic impact of measurable residual disease in acute myeloid leukemia, and the potential ways, both now and in the future, that such testing may rationally guide therapeutic decision-making.

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Section: Polymerase Chain Reaction-based Measurable Residual Disease mentioning

confidence: 99%

How close are we to incorporating measurable residual disease into clinical practice for acute myeloid leukemia?

Short

Ravandi

2019

Haematologica

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“…[20][21][22] Currently available evidence suggests that optimal outcomes are achieved when patients with CBF-AML obtain either a molecular remission by RT-qPCR or very significant reductions in RUNX1-RUNX1T1/CBFB-MYH11 transcripts with induction and postremission therapy (defined as at least a > 3 log reduction of transcript levels from baseline after consolidation therapy); 20,22,39 higher intensity regimens may lead to deeper log reductions after chemotherapy. 20,22,40…”

Section: Core-b Ind Ing Fac Tor Leuk Emiamentioning

confidence: 99%

“…Recent studies have highlighted the heterogeneity of the disease by identifying subsets of patients with distinct risks of disease recurrence based on the degree of reduction in RUNX1‐RUNX1T1/CBFB‐MYH11 transcripts . Currently available evidence suggests that optimal outcomes are achieved when patients with CBF‐AML obtain either a molecular remission by RT‐qPCR or very significant reductions in RUNX1‐RUNX1T1/CBFB‐MYH11 transcripts with induction and postremission therapy (defined as at least a > 3 log reduction of transcript levels from baseline after consolidation therapy); higher intensity regimens may lead to deeper log reductions after chemotherapy . Moreover, emerging evidence from a study by Jourdan et al suggests that information from post‐treatment RUNX1‐RUNX1T1 transcript levels may be preferable over high WBC or KIT / FLT3 mutational status to identify patients with high‐risk t(8;21)(q22;q22) AML, as only MRD but not the other factors had a significant prognostic impact in multivariate analyses.…”

Section: Core‐binding Factor Leukemiamentioning

confidence: 99%

Clinical implications of molecular markers in acute myeloid leukemia

Käyser

Levis

2018

European J of Haematology

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The recently updated World Health Organization (WHO) Classification of myeloid neoplasms and leukemia reflects the fact that research in the underlying pathogenic mechanisms of acute myeloid leukemia (AML) has led to remarkable advances in our understanding of the disease. Gene mutations now allow us to explore the enormous diversity among cytogenetically defined subsets of AML, particularly the large subset of cytogenetically normal AML. Despite the progress in unraveling the tumor genome, only a small number of recurrent mutations have been incorporated into risk-stratification schemes and have been proven to be clinically relevant, targetable lesions. We here discuss the utility of molecular markers in AML in prognostication and treatment decision making, specifically highlighting the aberrations included in the current WHO classification.

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“…These indices likely more accurately describe the spatial arrangement of the 18FDG uptake of the total area, with different SUV located within the tumor. 6,7 10. Burnett AK, Russell NH, Hills RK, et alOptimization of chemotherapy for younger patients with acute myeloid leukemia: results of the medical research council AML15 trial.…”

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confidence: 99%

“…Quantitative monitoring of MRD has been one of the most important prognostic parameters in CBF AML, because the presence of unique translocations make this subgroup of AML amenable to molecular monitoring of MRD. [7][8][9] Although MRD after 2 cycles of treatment was not impacted by presence of clonal interference in the analysis by Itzykson et al, MRD data were available in a smaller cohort (limited to after 2 cycles of therapy) and were included in a bivariate analysis only. Thus, the question of whether clonal interference is prognostic completely independent of serial MRD data has not been answered.…”

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confidence: 99%

Prognosis interfered with by clonal interference

Borthakur

2018

Blood

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predictive value, 89%) and low-risk (negative predictive value, 100%) patients compared with TLG alone. However, the analysis of the SUV histogram with AUC-CSH does not encompass most of the information contained in the image in disregard of the spatial heterogeneity of the 18FDG uptake within a given metabolic volume, which can be characterized by textural indices. These indices likely more accurately describe the spatial arrangement of the 18FDG uptake of the total area, with different SUV located within the tumor. 6,7 10. Burnett AK, Russell NH, Hills RK, et al.Optimization of chemotherapy for younger patients with acute myeloid leukemia: results of the medical research council AML15 trial.

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Response kinetics and factors predicting survival in core-binding factor leukemia

Cited by 25 publications

References 15 publications

How close are we to incorporating measurable residual disease into clinical practice for acute myeloid leukemia?

How close are we to incorporating measurable residual disease into clinical practice for acute myeloid leukemia?

Clinical implications of molecular markers in acute myeloid leukemia

Prognosis interfered with by clonal interference

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