Prognosis of Acute Myeloid Leukemia with Translocation (8;21): A Survey of 142 Cases Investigated in the JALSG AML97 Study.
Authors: Hatsumi Nahoko , Miyawaki Shuichi , Sakamaki Hisashi , Ohtake Shigeki , Yagaski Fumiharu , Mitani Kinuko , Matsuda Shin , Kishimoto Yuji , Miyazaki Yasushi , Asou Norio , Honda Sumihisa , Taniwaki Masafumi , Ohno Ryuzo 
Published: October 2019

Abstract
Background: Translocation (8;21) is one of the most common structural aberrations found in AMLand good response rates and a better DFS have been described in pts possessing it. Especially, the DFS rate may exceed 60–70% in younger pts given repetitive courses of HDAra-C. However, it was recently reported that a subtype of AML with t(8;21) showed a poor prognosis and this case also had the KIT mutation. As a result, we retrospectively analyzed the prognosis of AML pts with t(8;21) prospectively enrolled in the JALSG AML97 study.
Patients and Methods: Between 1997 and 2001, JALSG AML97 enrolled 809 pts previously untreated for AML and pts with M3 were excluded. From the 789 eligible pts, we selected the subjects with t(8;21) for this study. Induction therapy consisted of cytarabine and idarubicin. All CR pts were randomized to receive either four courses of standard dose consolidation therapy without maintenance therapy or three courses of standard dose consolidation with 6 courses of maintenance therapy. HDAra-C was not administered in the JALSG AML97 study. Peripheral blood and bone marrow smears and karyotypes were reevaluated by the central review committees. Any patients who underwent SCT were censored at the date of SCT. The Kaplan-Meier method was used to estimate OS and DFS. For comparisons of OS or DFS, the log rank test was used.
Result: Cytogenetic studies were performed in 783 patients (99.2%) and only 15 studies resulted in failure. One hundred forty-two (18.5%) of those pts showed t(8;21). The median age was 43 yrs (15–64). The male: female ratio was 95: 47. The distribution of FAB types was as follows: AMLM2, 130; M4, 6; M1, 5; and M5, 1. A total of 69 (48.6%) pts had a sole t(8;21), 46 (32.4%) had a loss of a sex chromosome, and 27 (19.0%) had other cytogenetic abnormalities. The CR rate was 90.0%. Thirty-two pts underwent two courses of induction therapy. The early death (< one month) rate was 1.4% (2/142). Only a high WBC count (>=10x109/L) was found to be a marginally significant prognostic factor (p=0.0517). The estimated OS rate at 5yrs was 53.6%, and the DFS of the CR pts was 41.2%. We found no relationship between OS or DFS and the following factors: age, gender, karyotypic abnormality, performance status, the percentage of MPO positive blasts, the presence or absence of Auer rods, the platelet count, the number of induction therapies for CR and the type of postremisson therapy. However, two factors, the WBC count and the percentage of blasts in bone marrow were found to be strongly predictive factors for the outcome. For the pts with a WBC count >=10x109/L, the DFS rate at 5yrs was 30.8%, while for the pts with less than 10x109/L, it was 48.8% (p=0.0215). For the pts with blast >=50% and less than 50%, the DFS rates at 5yrs were 32.2% and 56.7% (p=0.0087), respectively. According to these two factors, a poor risk group (N=30, 21.0%) was thus identified. They had a WBC count >=10x109/L and blast >=50%. The DFS rate at 5yrs was only 22.3 % in the poor risk group while that of the other pts was 48.9% (P=0.0003).
Conclusion: This study confirmed that all AML pts with t(8;21) shows a high response rate and a good prognosis, thus indicating that this favorable AML group includes a poor risk group which can be identified based on the WBC count and the blast percent in the bone marrow.