General AML

KIT mutation type in patients with t(8,21) acute myeloid leukemia have different prognoses

A group of Chinese researchers aimed to retrospectively evaluate the prognostic impact of individual KIT mutation types in patients with acute myeloid leukemia (AML). The results of this study were reported in the August 2018 issue of Blood Cancer Journal.

In this retrospective study, 275 patients (median age at diagnosis = 36 years, range, 16–69) with t(8;21) AML who were diagnosed and treated between June 2005 to December 2017 at Peking University People’s Hospital were analyzed for KIT mutational patterns.

Patients included in this study were treated with induction therapy consisting of the standard 3+7 regimen or homoharringtonine, aclarubicin and cytarabine regimen. Among 263 patients achieving complete remission, consolidation chemotherapy included either intermediate dose cytarabine-based chemotherapy, chemotherapy followed by autologous hematopoietic stem cell transplantation (HSCT), or chemotherapy followed by allogeneic HSCT. Dasatinib was used in some patients with KIT mutations.

Key findings:
  • Median follow-up time: 20 (2–93) months
  • Twenty-two types of KIT mutation were detected in 114 (41%) patients
    • Sole and compound (combination of two types) mutations were observed in 103 and 11 patients respectively
    • Patients had KIT mutations in exon 17 (37.8%) and exon 8 (5.1%)
    • Most prevalent mutations were exon 17 D816, exon 17 N822, exon 8 deletion-insertion and exon 17 D820
  • 3-year relapse-free survival (RFS) in patients with sole D816 mutation and those with no mutation: 33.7% (95% CI, 17.3 – 50.9%) vs 69.7% (95% CI, 59.9 – 77.6%), P < 0.0001
  • 3-year overall survival (OS) in patients with sole D816 mutation and those with no mutation: 54.9% (95% CI, 37.9–69.1%) vs 77.6% (95% CI, 68.3–84.5%), P < 0.0001
  • 3-year OS and RFS rates were similar among patients with the sole N822 mutation, exon 8 mutation, and no mutation
  • Patients with exon 17 D820 had significantly lower 3-year RFS than patients with no mutation: 20.0% (95% CI, 0.8–58.2%) vs 69.7% (95% CI, 59.9–77.6%), P = 0.0050

In summary, exon 17 D816 and D820 mutation were associated with an adverse prognosis while exon 17 N822 and exon 8 have a similar prognosis to no mutation.

Key limitations of this study include its retrospective nature, lack of data on other genes and the treatment regimen used in patients included in this study were not uniform.

In conclusion, the findings of this study demonstrate that individual KIT mutations have distinct prognoses in adult patients with t (8;21) AML. The authors noted that the findings of their study “would be helpful for a more precise stratification and for directing the appropriate treatment in t(8;21)”.

References
  1. Qin Y. Z et al. Heterogeneous prognosis among KIT mutation types in adult acute myeloid leukemia patients with t(8;21). Blood Cancer J. 2018 Aug 7;8(8):76. DOI: 10.1038/s41408-018-0116-1.
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