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

Background Studies evaluating the impact of 11q23 / KMT2A / MLL translocations on post-transplant outcomes as compared to other intermediate- and adverse-risk cytogenetic characteristics are lacking. Methods We considered 8709 AML patients from the CIBMTR database for inclusion. We evaluated relapse, non-relapse mortality (NRM), disease-free survival (DFS), and overall survival (OS) for patients who were transplanted in CR1 stratified by presence of 11q23 rearrangement, intermediate- or adverse-risk disease. Assignment of cytogenetic risk was performed by hand, based on the 2010 AML-MRC Classification System. A multivariate analysis was performed using a Cox proportional hazards model. Results Characteristics of 3779 patients, selected based on disease and donor type, HSCT in CR1, and availability of data, are shown in Figure 1. Of these, 426 patients had an 11q23-rearrangement, 2384 had intermediate-risk disease, and 969 had adverse-risk disease. Of the patients with 11q23 translocations, 112 (26%) had t(9;11), 62 (15%) had t(11;19), 41 (10%) had t(6;11), 28 (7%) had t(10;11), and 47 (11%) had other partners. No partner was provided in 136 cases (32%). Figures 2 and 3 show the DFS, OS, NRM, and relapse data stratified by cytogenetic category. Based on the multivariate analysis, DFS was lowest in adverse-risk patients (HR for death 1.47, 1.26 for MLL, p Stratification of outcomes by translocation partner did not yield any statistically significant differences between groups, however a descriptive analysis of these data will be presented. Measurable residual disease (MRD) status did not appear to play an independent role in NRM or in OS. However, the multivariate HR for relapse in patients with MRD-positivity was 1.23, p Conclusions Patients with MLL-rearranged AML had post-HSCT DFS and OS that were more similar to patients with adverse-risk disease than to those with intermediate-risk characteristics. MLL patients had a higher probability of relapse than intermediate-, but not adverse-risk, patients. NRM was similar among all groups. Both prognostic classification and MRD status independently contributed to the risk of relapse and DFS, but MRD was not an independent factor in predicting NRM or OS. Our study suggests that patients with MLL rearrangements do almost as poorly as those with adverse-risk disease and that novel approaches for this high-risk population represent an urgent unmet clinical need.