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IDH Mutation Location Affected Relapse Risk After AML Transplant

Overall, the presence of IDH mutations at diagnosis of acute myeloid leukemia (AML) did not have a strong prognostic effect after hematopoietic stem cell transplantation (HSCT); however, certain IDH mutation locations had a higher association with risk of relapse after transplant, according to a recent study.

Researchers led by Marius Bill, MD, PhD, of The Ohio State University, analyzed 292 patients with AML who received HSCT in complete remission or complete remission with incomplete peripheral recovery.

In AML, the prognostic impact of IDH mutations in patients consolidated with chemotherapy remains ambiguous with differing results in some larger retrospective studies,” the researchers wrote. “After consolidation with HSCT, the prognostic impact is even less clear.

Therefore, the researchers looked at IDH mutation status at diagnosis and at transplant as a potential marker for minimal residual disease (MRD). About 24% of the included patients had IDH mutations at diagnosis; 11.4% had IDH1 mutations and 14.0% had IDH2 mutations. The presence of IDH mutations did not have a prognostic impact when consolidated with HSCT.

However, the researchers did find that IDH1 R132 and IDH2 R172 MRD positivity in remission at transplant was associated with increased risk for relapse. In contrast, IDH2 R140 mutations had no such association. Patients with IDH1 R132 and IDH2 R172 MRD positivity also had shorter event-free and overall survival, but the difference was not statistically significant.

In our cohort, IDH2 R140 mutations behaved more like a clonal hematopoiesis related aberration, while IDH1 R132 and IDH2 R172 harbored AML disease specific features,” the researchers wrote. “In the context of consolidating HSCT in IDH mutated AML it will be interesting to see if deeper remissions – defined by IDH MRD variant allele frequency at HSCT – by novel induction concepts and/or trials testing IDH inhibitors as maintenance treatment (e.g., after HSCT) will improve outcomes of IDH mutated AML patients in the future.

Bill M, Jentzsch M, Bischof L, et al. Impact of IDH1 and IDH2 mutation detection at diagnosis and in remission in patients with AML receiving allogeneic transplantation. Blood Adv. 2022 Apr 5; doi: 10.1182/bloodadvances.2021005789.

 

 

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