Favorable Risk Group Acute Myeloid Leukemia in Children and Young Adult Treated in Uniform Protocol in Casablanca, Morocco. a Preliminary Analysis
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AbstractIntroduction: Treatment of Acute Myeloid Leukemia (AML) with in developing countries is challenging. 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. Improvement of supportive care with particular focus on prevention and management of infection and improved transfusion support is crucial for better overall outcome.Aim of the study: To evaluate the preliminary results (Complete remission, OS and EFS) in children and young adults with favorable risk group AML treated in a single center with AML MA 2011 protocol.Patients and methods: From January 2011 to December 2014, a uniform treatment protocol was conducted to treat patients with age ≤ 30 years with de novo AML with favorable risk group. The diagnosis was done according to FAB classification, MPO done systematically. Karyotype was performed on marrow sample (20 metaphases analyze at least), 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 3 consolidations. 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/m²q 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. The supportive care consisted of transfusion, antibiotic and patient and family education by hygiene team.Results: 39/159 patients (24.5%) had a favorable prognosis. They were 13 female and 26 male (Male/Female ratio of 2) with a median age of 21 years and the peak frequency was between 20-30 years (21 patients or 53.8%). Two groups were identified. (Table 1) The means WBC were 39.741 G/L (1.134-425.000G/L) and more than 50 G/L for 17 patients. t(8; 21) represented 71.8% of karyotype and was associated 14 times with other abnormalities: 8 loss of sex chromosome (6 -Y and -X 2), 2 deletions, 2 trisomy and 2 add. Inv16 or t (16; 16), 28.2% of case, was associated with a deletion once and once with trisomy. (Table 1) Molecular biology carried 7 times was positive in 4 cases all AML-ETO. Three patients died before treatment, two in hospital by septic shock (1), subarachnoid hemorrhage (1) and one at home. 36/39 patients were evaluable for the protocol. 17 patients with WBC > 50G/L received hydroxyurea prior to chemotherapy with good response for 16 (94.1%) and 1 (5.9%) death. The median average time from start of treatment was 15 days with a range of 1-52 days. After the two inductions 26 (74.3%) obtained a complete remission, 2 (5.7%) were in failure, and 7 (20%) died in hospitalization during induction 1. The cause of death was: 2 hemorrhage, 3 infections, 1 pulmonary embolism and 1 patient died at home.Conclusion: Therapeutic results are yet far from satisfactory. Complete remission could be improved with reduction of infection toxic deaths. Improvement of supportive care therapy may allow treating patients with intensified treatment with better outcome. Hydroxyurea is efficient to reduce WBC and for best conditions to initiate induction therapy.Table 1. Patient's characteristics All patients Group 1(age ≤15years) Group 2(age≥16 years) Number (%) Median age (Years) 39 (100%) 21 9 (23%) 10 30 (77%) 24 Male/Female 2 3.5 1.7 WBC>50000 (G/L) 17 2 7 FAB M1/M2/M4/M4Eo/other Immunophenotype 12/19/2/4/2 28 (71.8%) 1/7/1/0/0 7 (25%) 11/12/1/4/2 21 (75%) t(8 ;21) 28 (71.8%) 8 (88.9%) 20(66.7%) t(8 ;21)+ other anomalies 14 (50%) 5 (62.5%) 9 (45%) Inv 16 or t(16 ;16)Inv16 or t(16 ;16) + other anomaliesTreatmentComplete remission DeathFailureCauses of death infection/Hemorrhage/otherOSES 11 (28.2%) 2 (18.2%) 36*(92.3%) 26 (72.2%) 7 (18%) 2 2/3/2 51% 30.9% 1 (11.1%) 1 (100%) 9 (100%) 8 (88.9%) 1 (11.1%) 0 0/1/0 10 (33.3%) 1 (10%) 26 (86.7%) 18 (69.2%) 6 (23.1%) 2 (7.7%) 2/2/2 *One death after prephaseDisclosuresNo relevant conflicts of interest to declare.
