Homing in on allo-HSCT outcomes in AML patients with t(7;11)(p15;p15)

Translocation between 7p15 and 11p15 [t(7;11)(p15;p15)], is a chromosomal abnormality which results in a fusion of the Nucleoporin (NUP98) gene on 11p15 and the Homeobox A9 (HOXA9) gene on 7p15. The NUP98-HOXA9 fusion gene can contribute to leukemogenesis in Acute Myeloid Leukemia (AML) and is associated with poor outcomes in patients. There is a paucity of studies that have evaluated the transplant outcomes of AML patients with t(7;11)(p15;p15), hence the rationale for this study.

On 16^th November 2017, in a Letter to the Editor of Haematologica, Kaito Harada from Tokai University, Isehara, Japan, and co-authors reported results from their retrospective study which compared the transplant outcomes in AML patients with t(7;11)(p15;p15) versus patients with intermediate- or poor-risk AML variants. The study endpoints were Overall Survival (OS), Disease-free Survival (DFS), Relapse Rate and Transplant-related Mortality (TRM).

Using data from the Transplant Registry Unified Management Program, the authors identified 91 patients with AML harboring t(7;11)(p15;p15) who were enrolled between 1986–2014. They also identified 7,308 and 2,406 patients with intermediate- and poor-risk AML respectively with chromosomal changes other than t(7;11)(p15;p15). The median follow-up period was 1124 days in survivors (n = 4,278).

The key findings of the study were:

• OS at 3-years after allo-HSCT
  • t(7;11)(p15;p15) group: 40.1%
  • Intermediate-risk group: 48.0%
  • Poor-risk group:28.5%
  • Patients with t(7;11)(p15;p15) had significantly better OS than patients in the poor-risk group, P = 0.008
• DFS at 3-years after allo-HSCT
  • t(7;11)(p15;p15): 37.8%
  • Intermediate-risk group;: 44.8%
  • Poor-risk group:; 25.1%
  • Patients with t(7;11)(p15;p15) had significantly better DFS than patients in the poor-risk group, P = 0.006
• Cumulative incidence of relapse 3-years after allo-HSCT was significantly higher in the t(7;11)(p15;p15) group than in the intermediate-risk group; HR = 0.62 (95% CI, 0.43-0.89), P = 0.01
• 3-year TRM rate was not significantly different between the t(7;11)(p15;p15) and intermediate-risk group (21.8% vs3%, P = 0.26) or the poor-risk group (21.8% vs 30.7%, P = 0.5)
• Transplant outcomes in AML patients with t(7;11)(p15;p15) in first (n = 44) or second (n = 10) Complete Remission (CR)
  • 2-year OS in patients who underwent allo-HSCT in CR1 and CR2:60.6% vs3% respectively, P = 0.3
  • 2-year DFS in patients who underwent allo-HSCT in CR1 and CR2: 56.1% vs0% respectively, P = 0.056
  • OS (P = 0.005) and DFS (P = 0.001) were significantly higher in patients with t(7;11)(p15;p15) who underwent allo-HSCT in CR1 than in patients with high-risk (n = 37) AML
  • 2-year relapse rate in patients who underwent allo-HSCT in CR1 or CR2: 25.5% vs0%, P = 0.32
  • 2-year relapse rate was significantly lower in patients who underwent allo-HSCT in CR1 compared to high-risk AML patients; HR = 2.77, P = 0.009

Overall, Harada et al. concluded that their findings support the use of allo-HSCT in the treatment of patients with t(7;11)(p15;p15) AML, especially in first CR regarding the patients with superior outcomes. Unfortunately, allo-HSCT was found to be less effective in patients with high-risk disease or in second CR. In light of these findings, the authors stated that a larger prospective trial comparing allo-HSCT with standard chemotherapy is needed to confirm these results.