MLL Associated With Worse Post-Transplant Outcomes Than Other Cytogenetic Factors

In an analysis comparing the effects of MLL translocations with other cytogenetic characteristics on post-transplant outcomes in acute myeloid leukemia (AML), investigators found that survival rates are indistinguishable between patients with MLL-arranged disease and adverse-risk disease. However, the presence of an MLL translocation was associated with a higher risk of relapse than intermediate-risk cytogenetics. Results of the study were presented at the 2020 Transplantation & Cellular Therapy Meetings by Kamal Menghrajani, MD, from Memorial Sloan Kettering Cancer Center in New York.

The study included a total of 8,709 patients with AML who were enrolled in the Center for International Blood and Marrow Transplant Research database and had undergone hematopoietic cell transplantation (HCT) in first complete remission between 2007 and 2016. Patients were stratified by presence of 11q23 rearrangement (i.e., MLL fusions) as well as intermediate- or adverse-risk disease based on cytogenetics from the time of AML diagnosis. In addition to disease-free survival (DFS) and overall survival (OS), the investigators also evaluated rates of relapse and nonrelapse mortality.

Of the entire cohort:

  • 426 patients were included in the MLL group
  • 2,384 were classified as having intermediate-risk disease
  • 969 were classified as having adverse-risk disease

Among the 426 patients with 11q23 translocations, the following MLL subtypes were identified:

  • t(9;11) (n=112)
  • t(11;19) (n=62)
  • t(6;11) (n=41)
  • t(10;11) (n=28)
  • MLL other (n=47)
  • MLL undefined (n=136)

Characteristics were similar among the three groups: The median ages at HCT for the MLL, intermediate-risk, and adverse-risk disease groups were 46 years (range = 18-69), 55 years (range = 19-70), and 55 years (range = 20-70), respectively. Also, the proportions of patients who received an HLA-identical sibling donor were 25%, 31%, and 25%, respectively. Matched-unrelated donors were reported in 41% of the MLL group, 38% of the intermediate-risk disease group, and 39% of the adverse-risk disease group.

In multivariate analyses, the researchers observed that the DFS rate was lowest in the patients with adverse-risk disease (hazard ratio [HR] for death = 1.47; p<0.001), compared with the MLL group (HR for death = 1.26; p<0.002). The OS rate was similar between the MLL and adverse-risk disease groups (HRs of 1.32 and 1.45, respectively; p<0.001). Factors that predicted OS included: cytogenetics, age, Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI) score, white blood cell count at diagnosis, prior myelodysplastic syndromes (MDS), time to first complete remission (CR), time to HCT, donor type, and year of transplant (p<0.02 for all).

In contrast, patients with MLL fusions had a higher relapse risk than patients with intermediate-risk disease. Predictive factors for relapse were similar, and included cytogenetics, prior MDS, longer time to first CR, and shorter time to HCT (p<0.01 for all).

However, no difference was observed among the three groups regarding nonrelapse mortality (NRM). The following factors were predictive of NRM: age, performance status, conditioning regimen, and donor type (p<0.02 for all).

While measurable residual disease (MRD) status did not appear to independently predict NRM or OS, the investigators noted that the HR for relapse in patients with MRD-positivity was 1.23 (p<0.006). For the DFS analysis, the HR for death was 1.13 (p=0.04).

Based on these findings, the researchers concluded that patients with MLL-rearranged AML had post-HCT survival outcomes that “were more similar to patients with adverse-risk disease than to those with intermediate-risk characteristics.” The results also suggest that new approaches are needed for the high-risk population, as “they represent an urgent unmet clinical need.”

The authors report no relevant conflicts of interest.

Reference

Menghrajani K, Zhang J, Bo-Subait 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. Abstract #10. Presented at the Transplantation & Cellular Therapy Meetings, February 19, 2020; Orlando, FL.