General AML

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 16th 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.

References
  1. Harada K. et al. Outcomes after allogeneic hematopoietic stem cell transplantation in patients with acute myeloid leukemia harboring t(7;11)(p15;p15). Hematologica. 2017 Nov 16. DOI: 10.3324/haematol.2017.179804. [Epub ahead of print]