Peripheral Blood Absolute Lymphocyte Count at Diagnosis As a New Prognostic Factor in Acute Myeloid Leukemia with t(8;21) Patients

Background: The recurrent translocation t(8;21) represents approximately 12% of adult AML cases, and it involves the AML1 gene on chromosome 21 and the ETO gene on chromosome 8, which generates an AML1-ETO fusion protein. Previous studies have shown that t(8;21) AML with AML1-ETO fusion has a high complete remission rate with standard chemotherapy and a prolonged survival when sequential high-dose cytarabine is administered. However, prognosis of AML with t(8;21) is heterogeneous.

Method: In order to under the relationship between clinical characteristics and prognosis, we retrospectively analyzed data of 68 t(8;21) AML patients who diagnosed at the two centers of South Korea between November 2005 and September 2016.

Results: Median age was 56 (range, 17 to 82) and median follow up duration was 99.8 months (range, 278 to 150.8). Among 65 patients who achieved CR after induction therapy, 24 patients (37%) received allogeneic stem cell transplantation (allo-SCT). The median absolute lymphocyte count (ALC) at diagnosis was 2,093 × 10⁶/L (range, 400-7,200), with higher ALC (≥ 2,205 x 10⁶/L) being detected in 31 (45.6%) patients. Higher ALC at diagnosis was defined by an ALC cut-off of ≥ 2,205 x 10⁶/L determined by receiver operating characteristic analysis and this cutoff value discriminated (in terms of sensitivity and specificity) between survival and death (area under curve [AUC] = 0.740, P = 0.001). In univariate analysis, lower CD19 expression (≥ 35%), higher BM blast (≥ 55%) and higher ALC at diagnosis were significantly associated with poor overall survival (OS) and leukemia-free survival (LFS) rate. The 5-year OS and the 5-year LFS of patients with higher ALC were 26.2% and 26.7%, respectively, while those of patients with lower ALC were 83.9 % and 73.6%, respectively. Of note, when we analyzed OS of 139 patients with normal karyotype according to ALC, there was not significant difference of survival rate and the 5-year OS of higher ALC in normal karyotype AML patients was 21.2%. Both groups according to ALC in t(8;21) AML patients were comparable for age, sex and clinical features at diagnosis as well as the proportion of patients who received allo-SCT. WBC count (> 20,000 x 10⁹/L), ANC (> 1,500 x 10⁶/L), additional cytogenetic abnormality, and C-kit mutation at diagnosis have not significant impact on survival. Minimal residual disease (MRD) after the first consolidation therapy did not affect the survival rate. Interestingly, among the patients who achieved CR after induction therapy, patients in higher ALC group showed MRD after the first consolidation therapy with higher incidence (91.3% vs. 60.6%, P = 0.012). In multivariate analysis, higher BM blast (HR 3.97, P = 0.004) and higher ALC (HR 11.59, P < 0.001) remained independent prognostic factors for poor OS rates. Higher BM blast (HR 4.42, P = 0.001) and higher ALC (HR 7.37, P < 0.001) were also independent factors for worse LFS rates.

Conclusion: Higher ALC was a significant prognostic factor for LFS and OS in AML patients with t(8;21). Further study for the correlation of ALC and the mechanism of adverse prognosis are needed.