High Incidence and Curability of Patients with Acute Myeloblastic Leukemia (AML) and t(8;21) Treated On a Uniform Protocol in Casablanca, Morocco.

AML with t(8;21) is known to have a more favorable outcome when treated with adequate chemotherapy and supportive care. There have been minimal data on the characteristics and outcome of AML with this translocation in low-income countries.

We analyze the clinical and biological characteristics of a large population of children and adults with AML in Casablanca who had t(8;21) in relation to response, event-free (EFS) and overall survival (OS).

From 4/1/03 to 3/31/09, eligible patients were treated on the AML-MA2003 protocol at a single center. For patients presenting with WBC>50,000, hydroxyurea (HU) was given for 4 days prior to initiation of standard induction. Treatment included two induction courses of cytarabine, 200 mg/m²/d (days 1-7) and daunomycin 50 mg/m²/d (days 1-3); consolidation was stratified by age: those '20 years had two courses of Capizzi high-dose cytarabine, 2 g/m2 q 12h (days 1-4) with L-asparaginase, 6000 units/m2 day 4; those >20 years had one or two courses of high-dose cytarabine, 1 g/m2 q 12h (days 1-4) with daunomycin 50 mg/m²/d (day 1-3), and maintenance with oral 6-mercaptopurine 60 mg/m²/d and weekly sc cytarabine 40 mg/m² for 18 months. Events included death, relapse, progression, and abandonment.

85 of 535 (15.8%) patients with karyotype results had t(8;21), including 40 with only t(8;21), 25 with additional loss of a sex chromosome, 5 with del (9), and 15 with other cytogenetic abnormalities. Characteristics of the t(8;21) group are shown in the Table. Five adults were ineligible for protocol therapy, due to secondary AML (n=1), refused (n=1) and early death (n=3). Of 33 children (age < 20 years), 28 completed all 4 courses of planned therapy. Five deaths occurred on therapy (1 failure, 4 toxicity) and 11/28 relapsed later, 8-14 months after end therapy. Of 47 adults who received the first induction course, 35 went on to 2^nd induction, 34 received 1^st consolidation, 22 completed both courses of induction and consolidation, and 20 completed maintenance. There were 12 deaths on therapy and 12 relapses after therapy completion. Overall, 30/80 patients did not complete prescribed therapy: 14 deaths, 1 failure, 4 abandonment, 11 complete remission). 7/8 children and 4/4 adults with t(8;21) had an early response (50% decrease in blasts) to HU. The complete remission rate (CR) after two courses of induction therapy was 91% for children and 72.5% for adults. The 2-year EFS and OS for the patients with t(8;21) was 32% (standard error [SE] 6.3%) and 59% (SE 7.3%) respectively. There was not a significant difference in 2-year EFS by sex (p=0.18), age ' 20 years vs older (p= 0.08), or presence of additional cytogenetic abnormalities accompanying the t(8;21) (p=0.98)

t(8;21) in Morocco occurred in 15.8% of cases, more frequently than the 7 to12% reported. It was associated with a high incidence of extramedullary disease, FAB M2, frequent deletion of a sex chromosome, preponderance of males, and young age. A third of these favorable-risk AML patients survive event-free 2 years from diagnosis despite the problem of abandonment of therapy and suboptimal supportive care.

No relevant conflicts of interest to declare.