MRD Positivity in Two IDH Variants Associated with Higher Post-HSCT Relapse Risk in Patients with AML

A large retrospective analysis of patients with acute myeloid leukemia (AML) who underwent hematopoietic stem cell transplantation (HSCT) has found that, although in general the presence of IDH mutations in AML at diagnosis did not significantly influence prognosis, “IDH1 R132 and IDH2 R172 MRD positivity in remission at HSCT [was] associated with an increased risk of relapse, while IDH2 R140 mutations [was] not.” The analysis was published in Blood Advances in April.

Among 292 patients with a median age of 63 at diagnosis who received allogeneic HSCT at the University of Leipzig in Germany between 2007 and 2020, about 25% had an IDH mutation at diagnosis. The outcome analysis was restricted to 235 patients who received HSCT while in complete remission (CR) or CR with incomplete peripheral recovery (CRi). Median post-HSCT follow-up was 3.9 years.    

Material for ddPCR-based MRD detection was available for 44 patients with IDH1 or IDH2 mutations, of whom 33 (75%) had detectable IDH MRD. Using an optimized mutation-specific cut-off, the researchers “observed a strong relapse association of IDH1 R132 positivity or IDH2 R172 positivity, while IDH2 R140 MRD positivity [was] associated with an optically elevated but not significantly different [cumulative incidence of relapse] curve.”

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

  • 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 [published online ahead of print, 2022 Apr 5]. Blood Adv. 2022;bloodadvances.2021005789. doi:10.1182/bloodadvances.2021005789


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