Single Asian Centre Experience in Acute Myeloid Leukaemia with Translocation 8;21 [t(8;21) (q22;q22)/RUNX1-RUNX1T1]

Acute myeloid leukemia (AML) is associated with various acquired genetic changes in hematopoietic progenitor cells. Core binding factor (CBF) AML which consists of AML with t(8;21)(q22;q22)/RUNX1-RUNXT1 and inversion 16 are identified in 13-15% of patients with de novo AML. In both subtypes, the cytogenetic rearrangements disrupt genes that encode subunit of core-binding factor, a transcription factor that is essential in regulating normal hematopoeisis. AML t(8;21) tend to occur in younger age group and display favorable prognosis with chances of attaining complete remission up to 80%. However, relapse rate may reach 30-40%. Recently, more publications reported variable outcome of this subset of leukemia. Therefore, we set the study to evaluate the outcome of our cohort of AML patients with t(8;21) diagnosed between January 2008 and February 2015. We performed retrospective review of all patients who have been diagnosed as AML t(8;21) from our department's database. The data were collected from the electronic hospital information system (eHis). All data were analyzed in this non-randomized study on 30th June 2015. A total of 39 out of 812 AML patients diagnosed between January 2008 and February 2015 were included in this study with mean follow-up duration of 25.3 months (3-89 months). These patients were diagnosed from bone marrow assessment according the WHO 2008 classification with presence of t(8;21)(q22;q22) karyotype or detectable RUNX1-RUNXT1 fusion transcript. Mean age was 34.6 (13-72 year-old). Mean presenting white blood cell count was 25.3 x10^9/L (4.0-95.0x 10^9/L). 30 patients had karyotyping done at diagnosis, and 18 had no additional cytogenetic abnormalities. 84.6 % received standard daunorubicin and cytarabine (3+7) as induction chemotherapy and the remaining patients received other modified anthracycline-cytarabine combination chemotherapy. 25 patients achieved complete morphological remission (CR) after induction. 20 patients had sustained morphological CR after completion of cytarabine-based consolidation protocol and 13 still in CR until their last follow-up. 7 patients relapsed morphologically (mean duration of last chemotherapy 5.43 months) and only 2 patients managed to achieve and maintain CR after salvage chemotherapy and hemopoeitic stem cell transplant (HSCT). Those who relapsed while on consolidation chemotherapy (5 patients) also have dismal outcome as 4 of them died from progression of disease despite salvage chemotherapy and only 1 still alive and in CR after salvage chemotherapy and HSCT. In our cohort, 14 patients were not in CR after induction and received salvage chemotherapy. 2 of them remained refractory and eventually died. 12 patients achieved CR after salvage chemotherapy, followed by HSCT in 10 patients. 6 out of these 10 patients remained in CR until their last follow-up. 1 patient relapsed after HSCT and the other 3 died of transplant-related complications. Extramedullary disease was seen in 5 young males (age 13-27 years, involving 2 paraspinal, 1 lacrimal gland and 1 extraconal). 2 achieved CR after induction, while the other 3 achieved CR after consolidation, but 2 of them relapsed. 4 patients undergone HSCT and 3 remained in CR while 1 died of transplant-related complication. 30 patients had molecular monitoring throughout their treatment course. The best molecular response was unquantifiable fusion transcript, seen in 18 patients with mean survival of 33.2 months. The mean survival of 12 patients who had any level of molecular positivity was 26.5 months. Relapse rate was 38.5%, with relapse duration 1-14 months (mean 4.62 months). The overall survival in relapse/refractory group was 19.2 months, compared with 77.2 months in the other group. The analysis of our AML cohort t(8;21) suggests a favourable outcome, with short remission duration of less than 6 months in 73.3% who relapsed. Extramedullary disease and induction failure are poor prognostic features and HSCT is a feasible treatment strategy for this cohort. Role of PCR negativity as best molecular response during the treatment course as a prognostic indicator needs further evaluation.