Outcome of Acute Myeloid Leukemia in Children and Young Adults Treated with an Uniform Protocol in Casablanca, Morocco

Introduction :With the improvement in the risk assessment, therapeutic advances and supportive care, about 50% of children and young adults with newly diagnosed acute myeloid leukemia(AML) can be cured in high income countries. However similar survival advantages are not seen in patients from low or middle income countries.

In Morocco, the main causes of poor outcome in patients with AML are delayed diagnosis, early (before the start of treatment) and induction death, induction failure and therapy abandonment. In 2011, the National AML-MA-2011 protocol was developed to treat AML patients according to international standards and has focused on improving particularly supportive care, prevention and management of infection, transfusion support, implementation of hand hygiene, and education of patients, families and nurses. The goals of the AML-MA-2011 protocol were to obtain of favorable risk AML more than 70% complete remission rate, less than 10% on therapy mortality and event free survival (EFS) (4 years) of 40%.

Aim of this study : To evaluate and compare treatment outcomes (Complete remission rate, overall survival [OS] and EFS) of children (≤ 15 yrs.) and adolescents and young adults (AYA) (15-30 yrs) diagnosed with de novo AML and treated at a single center on AML-MA 2011

Patients and methods : From January 2011 to December 2015, eligible patient (age ≤ 30 yrs) with de novo AMLwere enrolled ona uniform treatment protocol. Patients with secondary AML, Down syndrome, those with acute promyelocytic leukemia or organ dysfunctions were excluded.

The diagnosis was confirmed according to the FAB classification using WHO criteria, At diagnosis BM MPO staining, immunophenotyping and lumbrteritisar puncture were performed. Karyotype was performed on marrow sample (with minimum 20 metaphases analyzed) using R banding technique. Patients with hyperleukocytosis (WBC≥ 50G/L) received as a pre-phase 4 days of hydroxyurea to 50mg/kg/day then 2 inductions and 2 consolidations. The two courses of induction associated cytarabine (100mg/m² q 12h for 10 days), Daunorubicin (50 mg/m² on days 2, 4, 6 for the first course, and on days 1, 3, 5 for the second course) and etoposide (100mg/m² for 5 days for the second course of induction). The consolidation included Cytarabine (3g/m²q 12h days1-3 for first and second course) plus Daunorubicin (30mg/m² on days 3, 4 at the first consolidation). L-Asparaginase 6000UI/m² on day 4 was give at second consolidation. All patients received CNS prophylaxis. Patients with CNS disease received addutional intrathecal.

The supportive care consisted of blood product transfusion, antibiotic and antifungal, and patient and family education by hygien team.

Complete remission (CR) was defined as normal clinical examination, no evidence of chloroma, peripheral counts recovery (ANC ≥ 1.0 G/L ; platelets ≥ 75 G/L without transfusion) and end of induction II bone marrow showed normal hematopoietic elements and <5% blasts.

Résultats :During the study period a total of 155 patients were enrolled, 41 were < 15 yrs (22 boys ; median age 7.8 yrs.). Of the 114 AYA enrolled, 48 were women and the median age was 23 yrs. In children median hemoglobin was 6.75g/dl and platelet 39.5G/L, 15/41 (36.6%) had AML2 and 36/41 (87.8%) had immunophenotyping. Among young adults 32/114 (28.1%) were hyperleucocytosis, 7.38g/dl and 52.81G/L were median hemoglobin and platelets respectively, 31/114 (29.8%) had AML1 and 89/114 (78.1%) had immunophenotyping. Cytogenetics was performed 90.2% of children and 95.6% of AYA. The median delay from diagnosis to treatment was 11.5 days in children and 29.9 days. Complete remission after two inductions was achieved in 28/41 (68.3%) children and 71/114 (62.3%) adults. The number of failure was 21 in age groups which 4 (9.8%) on children and 17 (14.9%) in young adults. The number of deaths in children is 9 (22%) of which 3 occurred in the first 15 days of induction and 6 from the 15th to 42nd day. AYA 26 (22.8%) deaths had been seen by registered including 5 in the first 15 days and 21 after. The causes of death were dominated by infections including 4 cases in children and 10 adults followed hemorrhage 3 cases among children and 10 adults. Leukostasis cases were recorded in 2 children 6 and young adults.

Analysis of the results is summarized in the table.

Conclusion : The therapeutic results of the protocol AML-MA 2011 were similar in both year groups, but are far from the goals of treatment.