General AML

The role of extramedullary involvement on the survival and characteristics of adult AML patients with t(8;21): A Korean Study

Acute Myeloid Leukemia (AML) t(8;21) subtype is associated with a high incidence of Extramedullary (EM) involvement which results in poor prognosis in this subgroup of patients. Post-remission therapy with Allogenic Hematopoietic Cell Transplant (allo-HCT) is usually not recommended for t(8;21) AML patients with EM involvement due to the lack of effect on survival outcomes. The role of EM involvement in adult AML patients with t(8,21) has not been clarified in association with HCT, hence the rationale for this study.

Sung-Soo Park from Seoul St Mary’s Hospital, Seoul, Korea and colleagues first published their data in Clinical Lymphoma, Myeloma & Leukemia on 17th September 2016.

In this study, the authors retrospectively studied 154 adult AML patients with t(8;21) and aimed to identify the clinical characteristics and treatment outcomes of patients with t(8;21) that either have an involvement of an EM site at diagnosis (EM-positive, n = 17) or do not have an involvement of an EM site at diagnosis (EM-negative, n = 137). 

The key results are:
  • Most frequently involved EM site at diagnosis in EM-positive t(8;21) patients was D spine (n = 8), L spine (n = 5), sacrum (n = 3), kidney (n = 2) and liver (n = 2)
  • Median age of patients in the EM-positive group versus EM- negative group; 27 vs 42 years, P = 0.013
  • Compared to EM-negative patients, there were more patients ≤ 45 years old in the EM-positive group; 57.7% vs 88.2%, P = 0.15
  • Leukocytosis (≥ 30 x 109/L) and high lactate dehydrogenase were higher in the EM-positive group compared to the EM-negative group, 41.2% vs 10.9%, P = 0.04 and 47.1% vs 14.6% , P = 0.004 respectively
  • c-kit mutations were higher in the EM-positive group compared to EM-negative; 58.8% vs 24.1%, P = 0.005
  • At diagnosis, factors associated with EM-positive t(8;21) included young age (≤ 45 years old; HR = 14.369, P =0.02), c-kit mutations (HR = 6.917, P =0.011) and leukocytosis (≥ 30 x 109/L, HR = 7.702, P = 0.014)
  • 3- year Overall Survival (OS) for patients at diagnosis in the EM-positive (n = 17) and EM-negative (n = 137) subgroup were 52.3% and 60.0% respectively; P = 0.658
  • 3- year Event Free Survival (EFS) for patients at diagnosis in the EM-positive (n =17) and EM-negative (n =137) subgroup were 51.5% and 58.0% respectively; P = 0.496
  • 3- year OS for patients treated with allo-HCT in the EM-positive (n =12) and EM-negative (n = 57) subgroup were 66.7% and 69.7% respectively; P = 0.889
  • 3- year EFS for patients treated with allo-HCT in the EM-positive (n =12) and EM-negative (n = 57) subgroup were 65.6% and 69.3% respectively; P = 0.759

In summation, the authors noted that their study had a small sample size and the data used in their study did not originate from a prospective clinical trial. They however, highlighted that despite these limitations, they were able to identify characteristics and associated factors of AML with EM-positive t(8;21) such as young age, leucocytosis and c-kit mutations. Additionally, it was noted that CNS was the most involved EM site in these subgroup of patients.

With regards to patient outcomes; post-remission therapy with allo-HCT provided good survival outcomes in these patients. Furthermore, the authors suggested that allo-HCT was an effective option for post-remission therapy in adult AML patients with EM- positive t(8;21).

Abstract
BACKGROUND:

Acute myeloid leukemia (AML) with t(8;21)(q22;q22) is classified into a favorable-risk group. Extramedullary (EM) involvement has frequently been reported in this subgroup as resulting in a poor prognosis. However, characteristics or standard treatments of t(8;21) AML with EM involvement (EM-positive t(8;21)) have not yet been elucidated.

PATIENTS AND METHODS:

We retrospectively analyzed 154 adult AML patients with t(8;21). Among them, 17 were EM positive and 137 were EM negative at the time of diagnosis. EM involvement was evaluated only when a patient showed suspicious signs or symptoms. All EM-positive patients were treated according to a strategy based on allogeneic hematopoietic cell transplantation (allo-HCT).

RESULTS:

Central nervous system was the most frequently involved site (70.6%). EM-positive t(8;21) was associated with age ≤ 45 years, leukocytosis (≥ 30 × 109/L), and c-kit mutation compared to EM-negative t(8;21) in multivariate analysis. After intensive chemotherapy with or without local therapy, high-risk t(8;21) AML including EM-positive t(8;21) underwent allo-HCT for postremission therapy. Three-year OS (52.3% vs. 60.0%, P = .658) and event-free survival (51.5% vs. 58.0%, P = .496) were not different between the 2 groups. The subgroup of patients who underwent allo-HCT also showed similar outcomes.

CONCLUSION:

EM-positive t(8;21) was associated with young age, leukocytosis, and c-kit mutation, and central nervous system was frequently involved. Allo-HCT resulted in good outcomes in EM-positive t(8;21).

References
  1. Park S. S. et al., Characteristics and Survival Outcome Analysis of Extramedullary Involvement in Adult Patients With t(8;21) Acute Myeloid Leukemia. Clin Lymphoma Myeloma Leuk. 2017 Jan; 17(1): 38-42: DOI:10.1016/j.clml.2016.09.001. Epub 2016 Sep 17.