Minimal residual disease monitoring based on FLT3 internal tandem duplication in adult acute myeloid leukemia

Abdelhamid, Emna; Preudhomme, Claude; Hélevaut, Nathalie; Nibourel, Olivier; Gardin, Claude; Rousselot, Philippe; Castaigné, Sylvie; Gruson, Bérengère; Berthon, Céline; Soua, Zohra; Renneville, Aline

doi:10.1016/j.leukres.2011.11.002

Cited by 50 publications

(46 citation statements)

References 38 publications

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“…Additional stable molecular markers with potential for development for MRD monitoring include DNMT3A 63 and CEBPA 64 . Despite initial concerns that tracking FLT3-ITD mutation would not be informative due to concerns regarding stability 65 using more sophisticated techniques 66 this mutation has been shown to be highly predictive for relapse risk 67, 68 . It is likely therefore that clinical laboratories will have to offer, or contract with a reference laboratory for, a portfolio of RQ-PCR MRD assays, which will increase as next generation sequencing (NGS) technology increases the number of viable molecular targets 3 .…”

Section: ) Pcr For Mutated or Rearranged Sequence For Mrd In Non-cbfmentioning

confidence: 99%

Minimal residual disease in acute myeloid leukaemia

2013

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Technological advances in the laboratory have lead to substantial improvements in clinical decision-making by the use of pre-treatment prognostic risk stratification factors in acute myeloid leukemia (AML). Unfortunately similar progress has not been made in treatment response criteria, with the definition of “complete remission” in AML largely unchanged for over half a century. Several recent clinical trials have demonstrated that higher sensitivity measurements of residual disease burden during or after treatment can be performed, that results are predictive for clinical outcome and can be used to improve outcomes by guiding additional therapeutic intervention to patients in clinical complete remission but at increased relapse risk. We review here these recent trials, the characteristics and challenges of the modalities currently used to detect minimal residual disease (MRD), and outline opportunities to both refine detection and better clinically utilize MRD measurements. MRD measurement is already the standard of care in other myeloid malignancies such as chronic myelogenous leukemia (CML) and acute promyelocytic leukemia (APL). It is our belief that response criteria for non-APL AML should be updated to include assessment for molecular complete remission (mCR) and that recommendations for post-consolidation surveillance should include regular monitoring for molecular relapse as a standard of care.

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Section: ) Pcr For Mutated or Rearranged Sequence For Mrd In Non-cbfmentioning

confidence: 99%

Minimal residual disease in acute myeloid leukaemia

2013

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“…NPM1 mutations can be targeted in one-third of adult and less than 10% of childhood AML [10,11], and DNMT3A mutations in 15-20% of adult and 2% of childhood AML [12][13][14]. FLT3-internal tandem duplications (ITDs), found in approximately 25% of adult and 15% of childhood AML [15,16], are also possible MRD targets [17][18][19][20][21], as are mutations of CEPBA and MLL-partial tandem duplications [22]. In essence, the majority of AML cases should have distinctive genetic markers that can be adapted as targets for MRD.…”

Section: Molecular Detection Of Minimal Residual Diseasementioning

confidence: 99%

Should evaluation for minimal residual disease be routine in acute myeloid leukemia?

Coustan‐Smith

Campana

2013

Current Opinion in Hematology

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“…20,21 Using FLT3 mutation as an MRD marker has not been standardized or demonstrated in large studies; however, several small studies have suggested that FLT3 mutations may be useful as an MRD marker, especially when sensitive methods are employed. [22][23][24][25] In our limited numbers, FLT3-ITD mutations was negative in all tested patients while some of them had residual disease by other meth- …”

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confidence: 63%