No abstract

Treatment of acute myeloblastic leukemia in children, adolescents and young adults (AYA) is a challenge in low-income countries. To evaluate treatment outcomes of children (B 15 years) and AYA (15-30 years) diagnosed with novo AML and treated in a single center according to the AML-MA 2011 protocol. From January 2011 to December 2015, eligible patients (age B 30 years) with novo AML had been enrolled on a uniform treatment protocol. The diagnosis was confirmed according to the FAB classification using the WHO 2008 criteria. Patients with WBC C 50 G/L had pretreated 4 days of hydroxyurea followed by two inductions and two consolidations. Supportive care consisted of transfusion of labile blood products, antibiotics and antifungals, and patient and family education by the hygiene team. 155 patients were recruited, 41 were \ 15 years old (22 boys, median age 7.8 years). Of the 114 AYA enrolled, (48 women, median age 23 years). Complete remission after two inductions was 28/41 (68.3%) of the children, including 100% of the children in the favorable group and 71/114 (62.3%) of the AYA, 22 of whom (68.7%) were in the favorable group. The number of deaths among children was 6 (14.6%). The evaluation of the AML-MA-2011 National Protocol in the age groups of children and AYA reveals that the objective of treatment is almost achieved in terms of complete remission in the two age groups.

Background In low‐ and middle‐income countries, therapeutic options for advanced, refractory, or relapsing malignancies are limited due to local constraints such as cost of drugs, distance from oncology centers, and lack of availability of new anticancer drugs. Metronomics, which combines metronomic chemotherapy (MC) and drug repositioning, allows for the provision of new therapeutic options for patients in this setting. Aim of the study To evaluate the activity and toxicity of a metronomic regimen in Moroccan pediatric patients with refractory or relapsing malignancies. Patients and methods From July 2014 to January 2018, patients with refractory/relapsing solid tumors treated in five pediatric oncology centers were consecutively enrolled. The metronomic regimen consisted of 28‐day cycles with daily oral administration of cyclophosphamide (30 mg/m2) from days 1 to 21, together with oral etoposide (25 mg/m2) from days 1 to 21 followed by break of one week and daily valproic acid (20 mg/kg) from days 1 to 28. Results Ninety‐eight children (median age, 8 years) were included. Underlying malignancies were neuroblastoma (24 patients), Ewing sarcoma (18), osteosarcoma (14), rhabdomyosarcoma (14), and miscellaneous tumors (28). A total of 557 cycles were given (median: 6; range, 1‐18 cycles). One‐year progression‐free survival of our patients was 19%, and one‐year overall survival was 22%. Complete response was obtained in three cases (3%), partial response in 11 cases (11%), and tumor stabilization for more than six months in 28 cases (28%). Conclusion This three‐drug metronomic combination was well tolerated and associated with tumor response and disease stabilization in 42 patients even for a long period.

Cytogenetic abnormalities are frequently reported in the literature describing the presence of chromosomal rearrangements in important cases of acute myeloid leukemia (AML); the rate can reach 50–60% of cases of AML. Cytogenetic abnormalities represent an important prognosis factor, their analysis is crucial for AML; cytogenetic study permits to classify prognostic groups and indicate the treatment strategy and helps to improve the outcome of these patients and to increase their chances of cure. Hundreds of uncommon chromosomal aberrations from AML exist. This chapter summarizes chromosomal abnormalities that are common and classifies AML according to the World Health Organization (WHO) classifications from 2008 to 2016; we will discuss briefly gene mutations detected in normal karyotype (NK) AML by cutting-edge next-generation sequencing technology, like FLT3-ITD, nucleophosmin (NPM1), CCAAT/enhancer-binding protein alpha (CEBPA), and other additional mutations.

AIM:The goals of this paper are: to report the incidence of AML in elderly, to describe cytogenetic characteristics of this population, to observe rare and novel cytogenetic abnormalities and lastly, to compare our finding with that previously reported in the literature.METHODS:We conducted a retrospective analysis of 283 patients with acute myeloid leukaemia (AML) treated in our unit, we will report the incidence of AML in elderly, describe cytogenetic characteristics of this population, observe rare and novel cytogenetic abnormalities and compare our finding with that previously reported in the literature.RESULTS:Among the 283 patients, 157 (54.4%) patients performed the karyotype, the cytogenetic analysis failed in 17 cases (11%). Prognostic group distribution was found to be favorable in 8 patients (6%) with 6 cases of t (8; 21) and 2 cases of inv (16), intermediate group in 94 patients (67%), including 58 cases (41,5%) with a normal karyotype, and an unfavorable group in 38 patients (27%) including complex karyotype (15%), -5 or del 5q (3%), -7 or del 7q (3.5%), t (9; 22) (2%). Some rare anomalies were observed.CONCLUSION:However, the occurrence of a complex karyotype was more frequent than younger patients. In our unit, elderly benefit from supportive care, our study shows that it is a heterogeneous group and our treatment approach have to change especially for the patient from favourable risk group who can benefit from intensive chemotherapy. We have to improve our diagnosis with including molecular genetics that provides a documented substrate for a thoughtfully considered treatment plan.

AIM: The aim of the study was to improve the quality of pain management in Moroccan pediatric oncology units, the Moroccan Society of Paediatric Haematology/Oncology initiated a national quality improvement project in 2014 with the support of the Lalla Salma Foundation for Prevention and Treatment of Cancer. METHODS: To assess the current situation of pain management in Moroccan pediatric oncology patients, two cross-sectional surveys were conducted, involving patient/parental proxies and health-care providers’. RESULTS: The first survey concerned 108 care providers from five institutions. The second survey covered 155 children with cancer from the five Moroccan pediatric oncology units. Among them, 145 reported suffering from pain, which patients/families attributed to the underlying cancer (n = 85), to procedures and treatment (n = 46), or to both the cancer and procedures/treatment (n = 19). Procedural pain was mainly related to lumbar puncture and bone marrow aspirate. The majority of patients/parents reported that pain negatively impacted their emotional, physical, and social functioning. The majority of parents requested further information and communication about pain management. CONCLUSION: Both health-care providers and families of children with cancer in Morocco report need for pain management improvement, including in institutional and educational practices. This current baseline data have informed the development of our ongoing project including continuing education, training, and practice policies development.

BACKGROUND: Patients with acute myeloid leukemia (AML) and hyperleukocytosis are at high risk of early mortality due to pulmonary, renal, and central nervous system complications. Leukapheresis and low-dose continuous infusion of cytarabine and hydroxyurea (HU) have been used but their advantages and limitations are not well characterized. The University hospital in Casablanca, Morocco has a limited number of beds, and hence admissions must be prioritized. Here we report the effects of HU on the white blood cell (WBC) count and early mortality rate of patients with hyperleukocytic AML. METHODS: Between April 2003 and December 2006, patients with AML were enrolled on the AML-MA2003 protocol (2 induction courses of cytarabine and daunorubicin and 2 postremission courses that include intermediate-dose cytarabine). Patients with AML and hyperleukocytosis (WBC count >50 x 109/L) were immediately started on HU (50 mg/kg/day orally x 4 days), regardless of hospital bed availability. Response was evaluated after 4 days of HU; patients were considered responders if >50% reduction of the initial WBC count was observed. RESULTS: Ninety of 260 (34.6%) patients enrolled had hyperleukocytosis. Three patients were excluded, induction therapy started on the day of admission. Therefore, 87 patients (48 females, 39 males) were evaluable. The mean age was 32 years (range, 2–60); 29% were children (ages 2–20 years). The mean initial WBC count was 104x109/L (range 50–260 x109/L); 37 (42.5%) patients had WBC counts > 100x109/L. The French-American-British subtypes were M1 (45%), M2 (26%), M4 (12%), M5 (7%), and M0, M3, M6 and M7 (2.5% each); 5 cases were unclassified. Karyotypes determined for 65/87 cases revealed 13 (20%) favorable karyotypes [9 had the t(8;21); 3 had inv16; 1 had the t(15;17)], 30 (46%) intermediate-risk karyotypes, including normal karyotypes, and 22 (34%) unfavorable-risk karyotypes. Sixty-two (71%) patients were classified as responders. In an additional 3, the WBC count was reduced 25%–50%. In 22 (25%) patients, including 4 whose WBC counts increased, HU showed no cytoreductive effect. The mean WBC count after 4 days of HU was 24 x 109/L (range, 1.5–125 x109/L); 15 (17%) patients’ WBC counts remained >100x109/L. Four patients developed acute tumor lysis syndrome (TLS) (hyperuricemia and renal dysfunction) in response to HU. There were 5 (8%) early deaths (mean, 7 days after the start of HU; range, 4–14 days). All 5 patients had WBC counts > 100x109/L at diagnosis, and only 1 was a responder. This mortality rate does not differ from that (9%) observed among the 170 protocol patients who did not have hyperleukocytosis. Causes of death included infection (n=1), pulmonary and CNS leukostasis (n=1 each), TLS (renal failure and hyperkalemia, n=1), and intracranial hemorrhage (n=1). Among several factors (age, sex, FAB type, karyotype, WBC counts), only WBC count of ≤ 100x109/L was significantly associated with response to HU (P=0.01). The complete remission rate after first course of induction therapy was 43.5% for responders and 16% for non-responders (P=0.02). CONCLUSION: HU given orally for 4 days rapidly reduces the WBC count in pediatric and adult AML with hyperleukocytosis. The early mortality rate in this high-risk group treated with HU compares favorably with rates reported for similar patients. It remains to be determined whether initial response to HU is associated with overall outcome in AML.

Introduction: 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 prephase Disclosures No relevant conflicts of interest to declare.