Measurable residual mutated IDH1 before allogeneic transplant for acute myeloid leukemia
Gege Gui1,2, Niveditha Ravindra3, Pranay S Hegde3
1Fralin Biomedical Research Institute, Virginia Tech FBRI Cancer Research Center, Washington, DC, USA.
Abstract:
Measurable residual disease (MRD) in adults with acute myeloid leukemia (AML) in complete remission is an important prognostic marker, but detection methodology requires optimization. Persistence of mutated NPM1 or FLT3-ITD in the blood of adult patients with AML in first complete remission (CR1) prior to allogeneic hematopoietic cell transplant (alloHCT) associates with increased relapse and death after transplant. The prognostic implications of persistence of other common AML-associated mutations, such as IDH1, at this treatment landmark however remain incompletely defined. We performed testing for residual IDH1 variants (IDH1m) in pre-transplant CR1 blood of 148 adult patients undergoing alloHCT for IDH1-mutated AML at a CIBMTR reporting site between 2013 and 2019. No statistically significant post-transplant differences were observed between those testing IDH1m positive (n = 53, 36%) and negative pre-transplant (overall survival (OS): p = 0.4; relapse: p = 0.5). For patients with IDH1 mutated AML co-mutated with NPM1 and/or FLT3-ITD, only detection of persistent mutated NPM1 and/or FLT3-ITD was associated with significantly higher rates of relapse (p = 0.01). These data, from the largest study to date, do not support the detection of IDH1 mutation in CR1 blood prior to alloHCT as evidence of AML MRD for increased post-transplant relapse risk.
Insights
Detecting IDH1 mutations in blood before stem cell transplant does not predict relapse risk in acute myeloid leukemia (AML) patients. Only NPM1 or FLT3-ITD mutations indicate higher relapse rates post-transplant.
Area of Science:
- Hematology
- Oncology
- Transplant Immunology
Background:
- Measurable residual disease (MRD) is a key prognostic marker in acute myeloid leukemia (AML).
- Persistence of NPM1 or FLT3-ITD mutations before allogeneic hematopoietic cell transplant (alloHCT) predicts poor outcomes.
- The prognostic value of other mutations, like IDH1, for MRD in AML remains unclear.
Purpose of the Study:
- To evaluate the prognostic significance of IDH1 mutations in patients with AML undergoing alloHCT.
- To determine if IDH1 mutation detection in remission blood predicts post-transplant relapse.
Main Methods:
- Retrospective analysis of 148 adult AML patients with IDH1 mutations.
- Testing for residual IDH1 variants (IDH1m) in pre-transplant complete remission 1 (CR1) blood.
- Correlation of IDH1m status with overall survival (OS) and relapse rates post-alloHCT.
Main Results:
- 36% of patients (n=53) had detectable IDH1m in pre-transplant CR1 blood.
- No significant difference in OS or relapse rates between IDH1m-positive and negative groups.
- In co-mutated AML, only persistent NPM1/FLT3-ITD, not IDH1m, predicted higher relapse rates (p=0.01).
Conclusions:
- IDH1 mutation detection in CR1 blood does not identify AML patients at increased risk of post-transplant relapse.
- NPM1 and FLT3-ITD mutations remain critical MRD markers in AML.
- Further research is needed to optimize MRD detection methodologies for AML prognosis.
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