Outcome of acute Myeloid Leukemia in Adults Patients Treated According to Morocco National AML-MA-2011 Protocol in Casablanca, Morocco

Introduction

Treatment of AML in developing countries is a very great challenge. In Morocco, the major causes of therapy failure are delay in diagnosis, early (prior to start of therapy) and induction deaths, induction failures and abandonment of therapy. In 2011, the national AML-MA-2011 protocol was initiated to treat AML patients according to international standards and was focused on the improvement of supportive care with particular the prevention and management of infection, transfusion support, the patient, family and nurses education on hygien. The objective of this new protocol was to obtained more than 70% of complete remission, deaths in inductions less than 10%, and EFS at 4years at 40%. The aim of this study is to evaluate the results in adults AML patients treated with AML MA 2011 protocol in Casablanca Hematology Departement.

Patients and Methods : Were reviewed the data ofpatients (aged 18-60yrs) treated according to AML-MA-2011 protocol from 1st january 2011 to 31th december 2015. Patients with APL or secondary AML were excluded. AML was diagnosed by studying peripheral blood smears, bone marrow aspiration, and biopsy slides stained with May-Grünwald Giemsa and myeloperoxidase. Immunophenotypic and cytogenetic studies were performed at diagnosis on bone marrow samples. AML was defined as the presence of more than 20% of myeloblasts in the bone marrow. Subtype of AML was recorded according to French-American-British (FAB) classification. Karyotype was performed on marrow sample, R banding technique was used. WHO 2008 prognostic classification was adopted.

Patients with hyperleukocytosis (WBC≥ 50G/L) received as a pre-phase 4 days of hydroxyurea to 50mg/kg/day. The two courses of induction associated Cytarabine (100mg/m² q 12h (day 1-10)), Daunorubicin (50 mg/m² (day 2, 4, 6) for the first course, on days 1, 3, 5 for the second course) and etoposide (100mg/m² only at second course of induction). The consolidation included Cytarabine (3g/m² q 12h (day1-3) for first and second course and 1 g/m² (day1-3) on third course) plus Daunorubicin (30mg/m² (day 3-4 and day 1-3) at the first and third consolidation. L-Asparaginase 6000UI/m² on day 4 was give at second consolidation. Patients received CNS prophylaxis.

Platelet support was provided in the case of bleeding, or whenever the platelet count was less than 10 × 10⁹/L. For infections, Ceftazidime was the first line of antibiotic used. Amikacin was added for persistent fever beyomd 48-h or clinical deterioration. Imipenem was used for persistent fever. Additional antibiotic or antifungal or antiviral was dictated by clinical and biological findings.

Complete remission (CR) was defined as the absence of abnormal clinical symptoms and having less than 5% of myeloblasts in the bone marrow, absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count >1.0 × 10⁹/L; platelet count >75 × 10⁹/L; independence of red cell transfusions. The analysis of data was done by SPSS 18.0

Résultats : 559 adults patients were diagnosed for AML,323 was treated by AML-MA-2011 protocol from 2011-2015. The median age was 38 years (18-60), the sex ratio M/F was 1.10 ; the median hemoglobin (g/dl) was 7.15 (2.6-16.3) ; the median platelet (G/L) was 38.5 (1-620) ; the median leukocyte (G/L) was 17.97 (0.85-377). For cytology, according to FAB the dominants types was M1 : 98 (30.34%), M2 : 97 (30.03%), M4 : 51(15.78%). 249 (77.08%) patients had immunophenotyping. According to karyotype, 46 (14.24%) had good prognosis ; 216 (66.87%) was in intermediate group, 61 (18.88%) had adverse prognosis. Complete remission after two inductions was obtained with 197(60.99%) patients, inductions failure was noticed on 49(15.17%) patients, 98(30.34%) patients died during inductions cycles ; 152(47.05%) achieved the second consolidation cycles, 66 (33.50%) patients whose were in complete remission relapse. The OS at 3-years was estimated at 48.4%. The analysis of therapeutics results is summarized in the table.

Conclusion : The therapeutics results of AML-MA-2011 protocol in the treatement of adults AML patients are satisfactory but could be improved with reduction of infection toxic deaths and improvement of supportive care therapy.