[Prognostic value of residual disease detection in acute myeloid leukemia with normal karyotype and negative FLT3-ITD]. / Intérêt pronostique de la détection de la maladie résiduelle dans les leucémies aiguës myéloïdes avec caryotype normal et FLT3-ITD négatif.

INTRODUCTION: Complete remission (CR) in patients with acute myeloid leukemia (AML) is still morphologicaly defined, thus corresponding to a wide range of tumor burden. OBJECTIVES: we aimed to evaluate the residual disease (MRD) status in patients with AML, as well as perform a molecular analysis of the FLT3/ITD gene in patients with normal karyotype. MATERIAL AND METHODS: adult patients with AML, diagnosed according to the WHO 2016 criteria, were included. MRD was detected using flow cytometric techniques after induction treatment resulting in CR. RESULTS: thirty patients met our inclusion criteria. 83 % of them had an intermediate risk status, 67 % of which (20/30) having a normal karyotype. MRD and leukemic stem cell (LSC) positivity in this group was predominant with considerable decrease in benign progenitor count. The relapse-free survival (RFS) in the group of MRD negative patients with normal cytogenetics and non-mutated FLT3 gene was better than the RFS in all of our patients studied. CONCLUSION: MRD and LSC are powerful prognostic factors for relapse. They should be routinely integrated to guide better management of AML.

Prognostic Impact and Phenotype of Residual Acute Myeloid Leukemia Stem Cells.

BACKGROUND: Leukemia stem cells (LSCs) have been demonstrated to be more therapy-resistant than leukemic blast cells reflecting measurable residual disease (MRD). CD34+CD38- cell frequency is an independent factor for relapse prediction and could therefore be used in the future to improve MRD assessment in acute myeloid leukemia (AML). This protocol is designed to enable accurate and reproducible immunophenotypic detection of measurable residual stem cell disease necessary for proper therapeutic decision and report their prognostic value in AML patients. METHODS: Fifty-four Novo AML adult patients diagnosed in the onco-hematology service of the "20 August 1953" Hospital in Casablanca. We analyzed phenotype and frequency of CD45dim CD34+CD38- cells in bone marrow samples from patients with AML and non-myeloid malignancies using six-color flow cytometry and a simple one-tube essay. RESULTS: For evaluation of leukemic stem cells, our gate strategy was based on the selection of CD34+CD38 - stem cells and leukemia associated immunophenotype approach. Positivity of CD123 or/and aberrant expression of primitive markers CD117 and HLA DR on stem cells discriminate leukemia stem cells from normal hematopoietic stem cells. We reported a statistically significant difference between expressions of primitive markers (CD117 and HLA DR) on leukemic stem cells. In addition, the frequency of LSCs after complete remission in post-induction was persistent in 50% of AML patients. CONCLUSIONS: Overall, we show that CD34+CD38-CD123+ as a basic phenotype, with aberrant phenotype detection of HLA DR and CD117 markers on stem cells, contributes to detecting LSCs which indicates the poor prognosis.

[Imatinib in the treatment of chronic myeloid leukemia in Morocco]. / Imatinib dans le traitement de la leucémie myéloide chronique au Maroc.

INTRODUCTION: The treatment of chronic myeloid leukemia (CML) has been revolutionized by the advent of tyrosine kinase inhibitors. The results of the IRIS trial demonstrated the efficacy and long-term safety profile of Imatinib. The objective of our work is to report the results at 15 years of treatment of CML in chronic phase with Imatinib in Morocco. PATIENTS AND METHODS: Retrospective study realized at the hematology unit of CHU d'Ibn-Rochd in Casablanca, from January 2003 to September 2018, including all CML patients in the chronic phase at diagnosis, were treated with Imatinib for a minimum duration of 6 months. RESULTS: In total, 318 patients were collected, the median age was 41.5 years, the sex ratio M/F was 0.7, the Sokal score was high in 56% of cases. The complete hematological response at 3 months was 92%, the complete cytogenetic response at 12 months and the cumulative response were obtained in 43% (29/67) and 55% (153/279) of the cases respectively, the molecular response was evaluated in 125 patients witch 85% were on major molecular response. On a median follow-up of 44 months, the OS and EFS at 10 years were 86% and 59%, respectively. DISCUSSION: Our profile is characterized by a young age of the patients, the female predominance and a high Sokal score. The rate of complete cytogenetic response remains lower compared to what is described, however the survival rates as well as the tolerance were similar to those of the literature.

The influence of DNMT3A and DNMT3B gene polymorphisms on acute myeloid leukemia risk in a Moroccan population.

Acute myeloid leukemia (AML) is a very complex disease that is linked to environmental, genetic and epigenetic factors. Several Studies have found that aberrations in DNA methylation process play a crucial role in leukemogenesis. The aim of this case control study was to evaluate the association between rs1569686, rs2424913 polymorphisms located in DNMT3B gene and rs7590760 polymorphism located in DNMT3A gene and AML risk in a Moroccan population. MATERIALS AND METHODS: The present study was conducted in 142 cases of AML and 179 control subjects from the Moroccan population. Genomic DNA was isolated from whole blood samples by salting-out method and the genotype of the three polymorphisms was determined by the PCR-RFLP technique. RESULTS: The study results indicated that rs1569686 polymorphism was significantly associated with the risk of AML in dominant model (OR=1.72, 95 % CI 1.01-2.95, P=0.04), but not in recessive model. In stratified analysis by gender, statistically significant association between the rs2424913 CT genotype and AML was found among males (OR=2.05, 95 % CI 1.00-4.19, P=0.04). Similarly, the rs1569686 TT genotype was associated with an increase risk of AML (OR=3.21, 95 % CI 1.15-8. 98, P=0.02), this association was also found under dominant genetic model (OR=2.47, 95 % CI 1.07-5. 67, P=0.03) among males. However, the rs2424913 polymorphism was not associated with AML. CONCLUSION: Our findings have shown that rs1569686 polymorphism might be a risk factor of AML in males. While, the rs2424913 polymorphism was not associated with AML. Further studies with a large sample size are needed to validate our results.

Association of Multidrug Resistance Gene-1 (MDR1 C1236T) Polymorphism with the Risk of Acute Myeloid Leukemia in a Moroccan Population.

The human multidrug resistance MDR1 gene plays a crucial role in the absorption, transport, metabolism and elimination of harmful compounds. An impaired metabolism of these compounds related to genetic polymorphism may cause cancer such as acute myeloid leukemia AML. OBJECTIVE: The present study investigated the relationship between C1236T polymorphism and the risk of AML development in a sample of Moroccan population. METHODS: The present case-control study included 131 AML patients and 136 healthy controls. The MDR1 C1236T polymorphism was identified by PCR-RFLP method. Meta-analysis was performed to discuss our results. Statistical analyses were performed using SPSS, MetaGenyo and MedCalc. RESULTS: A positive association was found between the 1236TT mutant genotype and the risk of AML (OR 2.39; 95% CI 1.02-5.57, p= 0.04) compared to the wild type 1236CC. In addition, the recessive model revealed that carriers of 1236TT mutant genotype were more exposed to develop AML when compared to the combined 1236CC/CT genotype (OR: 2.27, CI: 1.01-5.05, p=0.04). The clinical parameters of AML showed no significant association. Meta-analysis demonstrated no statistically significant association between this polymorphism and AML susceptibility. CONCLUSION: Our study suggests that the MDR1C1236T polymorphism appears to be associated with the risk of AML. Further studies, including a large sample size, are needed to confirm these findings.

Cytogenetic profile of a representative cohort of young adults with de novo acute myéloblastic leukaemia in Morocco.

BACKGROUND: We analyzed the cytogenetic characteristics of a representative population of young adults with de novo acute myéloblastic leukemia (AML) treated in a single center institution. METHODS: Patients with de novo AML included were aged between 20 and 60 years. Cytogenetic analysis was done at diagnosis. Twenty cells were analyzed, although examination of lower numbers of metaphases was also acceptable if an abnormal clone was detected. FINDINGS: From 1/1/04 to 31/12/2014, among 1315 adult patients, 1055 (80%) patients were aged between 20 and 60 years. Karyotype was done in 927 (88%) patients and cytogenetic analysis failed in 32 cases (3·4%). Clonal abnormalities were observed in 520 (58%) patients. 175 (19·5%) were classified in the favorable group, 609 were in the intermediate group and 111 (12·5%) were in the adverse group. The most frequent chromosomal abnormality observed was t(8;21) in 112 (12·5%). Thirty three (3·7%) patients had t(15;17) and 30 (3·3%) had inv16, trisomy 8 was found in 47 (5·2%), 11q23 rearrangements in 32 (3·6%), 67 (7·4%) had a complex karyotype, -5/del(5q) and -7/del(7q) were seen in, respectively, 11(1%) and 27 (3%). Monosomy occurred in 115 (13%) patients, 70 (8%) responded to the definition of monosomal karyotypes. INTERPRETATION: This is the largest study done in Morocco, Africa and Middle East. Epidemiological studies involving different ethnic populations and geographic regions of the world should help unfold the true nature of environmental and genetic interplay in the development of AML. Our cytogenetic profile reveals some particularities when compared to other populations; it does not seem to be similar neither to eastern or western countries.

Acute Myeloid Leukemia (AML) In Elderly: Cytogenetic Characteristics of Patients Treated At Hematology and Pediatric Oncology Center in Casablanca.

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.

Secondary Thymoma among Adult Treated For Acute Lymphoblastic Lymphoma/Leukemia: Report of a Case and Review of the Literature.

BACKGROUND: Concomitant thymoma and T- lymphoblastic/leukaemia lymphoma is possible. Secondary thymoma after treatment for T-lymphoblastic/leukaemia lymphoma was also occasionally reported, although this is quite rare. CASE REPORT: We report a case of 44-year-old women with secondary thymoma after chemotherapy treatment for T Acute Lymphoblastic leukaemia/lymphoma. Diagnosis of lymphoblastic/leukaemia lymphoma was made in 2015 by morphological and histological study. The patient underwent Moroccan protocol for acute lymphoblastic leukaemia (MARALL) from 2015 to 2017 and achieved complete remission. One year later, the patient developed an anterior mediastinal mass, relapse was suspected, but the surgical biopsy was performed and histological, the mass showed thymoma. CONCLUSION: At the time of diagnosis of thymoma for a patient treated for T-lymphoblastic/leukaemia lymphoma it is necessary to eliminate a relapse because the distinction between thymoma and T-lymphoblastic/leukaemia lymphoma is sometimes difficult, and the association is possible.

[Primary colonic extranasal NK/T-cell lymphoma: about a case]. / Lymphome T/NK extra-nasal à localisation colique primitif: à propos d'un cas.

To better understand this cancer, we here report the case of a 43-year old patient diagnosed with localized and isolated primary colonic NK/T-cell lymphoma without associated enteropathy, treated wih 3 cycles of AspaMetDex with a poor response who died during treatment with a clinical picture of acute abdomen. Primary intestinal NK/T-cell lymphoma most commonly affects the young subject with poor prognosis. It is difficult to distinguish between intestinal NK/T-cell lymphoma and inflammatory or infectious intestinal disorders because of its non-specific clinical and endoscopic features. The histopathological and immunohistochemical data as well as the study of DNA allow to adjust the diagnosis and to classify this lymphoma according the European Enteropathy type T-cell lymphoma (ETL).

[Burkitt's lymphoma of the oral cavity: about a case]. / Localisation buccale d'un lymphome de Burkitt: à propos d'un cas.

Burkitt's lymphoma (LB) is a type of malignant non-Hodgkin's lymphoma originating from malignant B-cell transformation and proliferation. Positive confirmation is based on biopsy of the tumor mass or bone marrow aspiration revealing the presence of tumor cells. We here report the case of a young man, about twenty years old, addressed for post tooth extraction gingival swellings evolving for 1 month. Anatomopathologic examination after biopsy complemented by immunohistochemistry confirmed the diagnosis of Burkitt's lymphoma. Treatment was based on chemotherapy. Although Burkitt's lymphoma is rare, it is an aggressive tumor that represents a real public health problem, hence the role of the dentists in early diagnosis, in order to allow rapid and appropriate management of the disease which is vital to the healing process.

[Diffuse interstitial lung disease revealing adult T-Cell leukemia/lymphoma (HTLV-1)]. / Pneumopathie interstitielle diffuse révélant la leucémie-lymphome à cellules T de l'adulte HTLV1.

Adult T-Cell Leukemia/Lymphoma is a tumoral proliferation of activated mature T lymphoid cells whose causative agent is a retrovirus known as Human T-cell leukemia virus type 1. This virus rarely causes inflammatory bronchioloalveolar disorders. We report the case of a patient hospitalized with diffuse interstitial lung disease and whose etiological assessment revealed adult T-Cell Leukemia/Lymphoma (HTLV-1).

Acquired factor VII deficiency associated with acute myeloid leukemia.

Isolated acquired factor VII deficiency is a rare coagulopathy. It has been reported in 31 patients with malignancy, sepsis, postoperatively, aplastic anemia, and during bone marrow transplantation. We discuss, through a new case of acquired factor VII deficiency, the characteristics of this disease when it is associated with acute myeloid leukemia. Acquired factor VII deficiency in hematological diseases can be caused by intensive chemotherapy, infections, or hepatic dysfunction. The best treatment in developing countries remains corticosteroids associated with plasma exchange, frozen plasma, and antibiotics.

Naso-Sinusal T ALL With Aberrant Expression of CD56 Mimicking NK/T Non Hodgkin Lymphoma.

T-acute lymphoblastic leukemia (T-ALL) represents 25 % of cases of acute lymphoblastic leukemia (ALL) in adults. The clinical presentation is dominated by a elevated number of white blood cells and in immunophenotype the lymphoblasts are generally Tdt positive and variably express CD1a, CD2, CD3, CD4, CD5, CD7, and CD8. NK/T non Hodgkin lymphoma is presented as a single lesion often ulcerated with torpid evolution affecting the nasal cavity, nasopharynx and/or palate. CD56 expression is while characteristic of NK-cells, and is also expressed on a subset of normal T cells. Its expression in ALL does not exclude the diagnosis and seems to be a prognostic factor of this disease. We report the case of a young woman with nasal cavity tumor which was initially diagnosed as T-cell lymphoma. This diagnosis was finally revised to conclude to T-ALL with CD56 aberrant expression.

[Healthcare-associated infections in a paediatric haematology/oncology unit in Morocco]. / Infections associées aux soins dans une unité d'hématologie-oncologie pédiatrique au Maroc.

OBJECTIVE: HAI cause considerable morbidity and mortality and are associated with prolonged hospital stay and increased health care costs. To describe the incidence of HAI in paediatric cancer patients as the first step towards improving infection control policies. METHODS: A prospective surveillance study was performed in the Casablanca university hospital paediatric haematology/oncology unit over an 8-month period from January to August 2011. Data including extrinsic risk factors associated with HAI were recorded. RESULTS: The incidence of HAI was 28 per 1000 patient-days. The median age was 9.6 years and the most frequent diagnosis was acute myeloid leukaemia (32%). Neutropenia at diagnosis was significantly correlated with the risk of HAI. 55.7% of HAls were nosocomial fever of unknown origin. Gram-negative bacteria were the main pathogens (60%), gram-positive cocci were responsible for 26% of HAI and Candida for 14% of HAI. The length of hospital stay for patients with and without infection were 16.5 and 5 days, respectively (P < 0.001). Six of the 11 deaths were related to HAI. CONCLUSION: These findings suggest the need to evaluate infection control measures in order to reduce morbidity and mortality in paediatric haematology/oncology units.

[Reccurent pregnancy loss and 20210GA prothrombin mutation]. / Fausses couches à répétition et mutation 20210GA de la prothrombine.

Prothrombin mutation, in the same way as the factor V Leiden, is a thrombophilic state susceptible to induce both thrombosis and repetition of miscarriages at pregnancy woman. We report a case of 36 year-old woman who presented two miscarriages leaded to thrombophily state diagnosis by prothrombin mutation and among which two last pregnancies were led to their term thanks to anticoagulation.