General AML

Results from a CIBMTR study of patients with MLL-rearranged AML

Translocations at chromosome 11q23 involving the MLL gene are present in 3%–4% of patients with acute myeloid leukemia (AML). Because adult cases of AML with 11q23 abnormalities are rare, there are a lack of studies evaluating the impact of these translocations on patient outcomes.1 During the 2020 Transplantation & Cellular Therapy (TCT) Meeting, Kamal Menghrajani, Memorial Sloan Kettering Cancer Center,  New York, US, presented the results of a study by Center for International Blood and Marrow Transplant Research (CIBMTR)  evaluating the impact of MLL-rearranged AML on post-transplant outcomes as compared to intermediate- and adverse-risk disease.2

Methods2
  • 8,709 adult patients with AML from the CIBMTR database were included
  • Patients transplanted in first complete remission (CR1) were stratified by presence of 11q23 rearrangement, intermediate- or adverse-risk disease
  • Relapse, non-relapse mortality (NRM), disease-free survival (DFS), and overall survival (OS) were analyzed
  • Of the 8,709 eligible patients, 3,779 were selected based on disease and donor type, HSCT in CR1, and availability of data, of these:
    • 426 patients had an 11q23 translocation:
      • t(9;11): 26% (n = 112)
      • t(11;19): 15% (n = 62)
      • t(6;11): 10% (n = 41)
      • t(10;11): 7% (n = 28)
      • 11% (n = 47) had other translocation partners
      • For 32% (n = 136) no translocation partner was provided
    • 2,384 patients had intermediate-risk disease
    • 969 patients had adverse-risk disease
Results2
  • DFS was lowest in adverse-risk patients, hazard ratio (HR) for death:
    • adverse- risk, 1.47 (p < 0.001)
    • MLL, 1.26 (p = 0.002)
  • OS was shorter for the MLL- and adverse-risk groups:
    • adverse-risk, HR = 1.45 (p < 0.001)
    • MLL, HR = 32 (p < 0.001)
  • NRM was worse for patients with adverse-risk disease, with an HR of 1.17 (p = 0.05)
  • Relapse risk was higher for adverse-risk patients:
    • adverse risk, HR = 1.71 (p < 0.001)
    • MLL, HR = 1.27 (p = 0.01)
  • Relapse rates were similar for all translocation partners
  • For patients with measurable residual disease (MRD)-positivity:
    • HR for relapse, 1.23 (p < 0.006)
    • For DFS, HR for death, 1.13 (p = 0.04)
Conclusions2

In adult patients with MLL-rearranged AML, transplanted in CR1:

  • DFS and OS are very similar to patients with adverse-risk disease
  • MRD was a predictor of relapse and DFS, but not of NRM or OS
  • All translocation partners showed very similar relapse rates

All together these results demonstrated that adult patients with MLL-rearranged AML had a poor outcome, similar to patients with adverse-risk disease. New therapeutic approaches are needed for this population.

References
  1. Chen Y. et al. Prognostic significance of 11q23 aberrations in adult acute myeloid leukemia and the role of allogeneic stem cell transplantation. Leukemia. 2013 Apr; 27(4):836–42. DOI: 10.1038/leu.2012.319
  2. Menghrajani K. et al. MLL-Rearranged AML Is Associated with Poor Outcomes As Compared to Patients with Intermediate- and Adverse-Risk Disease: A CIBMTR Study of 3779 Adult Patients. Biol Blood Marrow Transplant. 2020 Mar 01; 26(3):S10–S11. DOI: 10.1016/j.bbmt.2019.12.074
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