t(1;4) translocation in a child with acute lymphoblastic leukemia: a case report.

BACKGROUND: Acute lymphoblastic leukemia is the most common childhood cancer, with an 80% frequency in children between 1 and 10 years old. The outcome and prognosis of acute lymphoblastic leukemia in children depends on various factors, such as age, clinical and biological features, and cytogenetic factors. CASE PRESENTATION: We report the case of a pediatric patient, a 4-year-old Moroccan female who was referred to the Hematology and Oncology Department of 20 August 1953 Hospital in Casablanca and diagnosed with B-cell acute lymphoblastic leukemia associated with a rare genetic chromosomal abnormality. CONCLUSION: Translocation (1;4)(p21;p15) is a relatively rare chromosomal abnormality found in human leukemia and was never described isolated in pediatric B-cell acute lymphoblastic leukemia patients. It showed a good evolution by complete remission and recovery of this patient after receiving all chemotherapy and after 8 years of follow-up.

Immunophenotype of Acute Lymphoblastic Leukemia: The Experience of University Hospital Centre Casablanca - Morocco.

BACKGROUND: Acute lymphoblastic leukemia (ALL) encompasses a group of lymphoid neoplasms that morphologically and immunophenotypically resemble B-lineage and T-lineage precursor cells. Our objective is to describe the immunophenotypic aspects of acute lymphoblastic leukemia (All) diagnosed by flow cytometry at the hematology laboratory of IBN ROCHD University Hospital Center and to compare them with those reported in other series. METHODS: This is a descriptive study over a period from August 2016 to October 2021, during a 5 year-and-2-month period. Immunophenotyping was performed at the flow cytometry unit on a Beckman-Coulter with 6 colors and 2 lasers in the hematology laboratory of the same hospital and data was collected retrospectively from the patients' files, their medical prescription files, kalisil software, and a data collection form we have established. RESULTS: The 440 patients had ages ranging from 1 month to 76 years, with a median of 9.5 years and the overall male-to-female ratio was 1.44. The immunological subtyping revealed that 82.5% of cases were B-ALL and 17.5% were T-ALL; of these B-ALL cases 230 (63.36%) were children (range: 0.1 - 15 years) and 134 (36.91%) were adults (range: 16 - 76 years); T-ALL were distributed in both age groups, 49 cases (37.7%) were children (range: 2 - 15 years) and 28 (21.56%) were adults (range: 18 - 63 years). All patients presented at least one abnormal blood count; thrombocytopenia has been observed in 89.4% of cases, anemia in 86.5% of cases, hyperleukocytosis in 79.8% of cases, leukopenia in 10.6% of cases, and pancytopenia in 4.8% of cases. The frequency of B-cell markers in B-ALL was found to be 363 (100%) for CD19, 323 (88.94%) for CD10, 290 (80%) for CD79a, and 73 (20%) for CD20. CD34 expression was found in 73 (20%) cases of B-ALL. HLA-DR was found in 54 (15%) cases, while TdT was found in 43 (13%) cases. Aberrant expression of myeloid antigens was found in 94 (26%) cases of B-ALL. Among T-ALL, the positivity of CD3 and CD7 was 100% (77 cases), while CD5 was positive in 58 (75%) cases. CD34 expression was found in only 19 cases of T-ALL. CD4 and CD8 expression was checked in only 9 adult patients and 4 pediatric cases. Out of them, 77.82% of cases were negative for both CD4 and CD8. CD4 and CD8 double positivity was seen in only 11.1% of cases, and 22.4% of cases showed either CD4 or CD8 positivity. CONCLUSIONS: We concluded that our study was similar to reports in the Americas and Europe, and it was the first large one that describes the immunophenotypic profile of ALL in the Moroccan population.

[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.

Diagnostic guidance for hereditary neutropenia in children: Narrative literature review.

In the era of genomics, orientation in the face of hereditary neutropenia still requires, first and foremost, a good clinical and cytological analysis. The thirty responsible genes now explain 60% of congenital neutropenia. These are rare since they are only found in 1‰ of all congenital neutropenia, estimated at 1% of the population. The clinical examination looks for phenotypes associated with syndromic hereditary neutropenia and cytology will guide this etiological research thanks to the data collected from blood count and bone marrow analysis. The objective of this narrative literature review is to provide an overview of the most recent literature regarding acquired and congenital chronic neutropenia and will provide a decision tree to guide towards aetiology. This will allow a better discussion with geneticists even if the genotype-phenotype correlation is not very strong.

Aberrant Phenotype in Acute Myeloid Leukemia: Hematology Laboratory Experiment of the University Hospital of Casablanca, Morocco.

BACKGROUND: Aberrant phenotypes in acute myeloid leukemia have variable frequencies and their prognostic value with adverse hematological and other biological prognostic factors is still controversial, despite several reports of clinical significance. To date, no study has been reported evaluating the incidence of these phenotypic aberrations in the Moroccan population. The aim is to evaluate the incidence of aberrant phenotype expressions in acute myeloid leukemia and correlate their presence with the different AML subtypes, and clinical and biological characteristics in Moroccan patients. METHODS: Fifty-four AML patients were diagnosed according to WHO classification 2016 criteria. Immunopheno-typing by flow cytometric analysis was performed to evaluate aberrant phenotypes on myeloblasts. RESULTS: The occurrence of lymphoid antigens in AML was higher (51.8%), which was closer to that reported in the literature. CD7 has been revealed to be the most commonly expressed lymphoid antigen. Besides, CD19 was expressed in all 3.7% of M2 AML subtype. However, we could find no statistically significant differences between these aberrant phenotypes regarding FAB subtypes or clinical and biological outcomes. The great majority of AML cases showed asynchronous expression (57%) with significant differences regarding FAB subtypes. CONCLUSIONS: Aberrant phenotypes might be associated with different leukemia subtypes that should be studied for a better understanding of their biological significance and adding important information for prognosis and, at the same time, could be of help when looking for minimal residual disease during morphologic remission.

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.

[Large granular lymphocyte CD3+CD56+ Leukemia revealed by ocular tumor]. / Leucémie à grands lymphocytes granuleux CD3+ CD56+ révélée par une tumeur oculaire.

Large granular lymphocyte leukemia (LGL) constitutes a heterogeneous entity with very different immunophenotypic, clonal and evolutionary characteristics. The most common LGL-T are CD3 +, CD8 +, CD16 +, CD57 +, CD56-. The majority of patients have a chronic disease, systemic signs are rare, and symptoms mainly result from neutropenia or associated autoimmune diseases. We report here a very special case of a 44-year-old woman patient diagnosed with aggressive LGL-T variant also expressing CD56.

[Multiple myeloma and autologous haematopoietic stem-cell transplantation without cryopreservation: experiences of the Clinical Hematology Department of Casablanca, Morocco]. / Myélome multiple et autogreffe des cellules souches hématopoïétiques sans cryoconservation: expérience du Service d´Hématologie Clinique de Casablanca au Maroc.

High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (AHSCT) is the gold standard treatment for multiple myeloma in subjects aged ≤ 65 years. In developing countries, AHSCT without cryopreservation reduces the costs of hospitalization and all necessary equipments. We conducted a longitudinal, prospective, open study to evaluate this procedure at the Department of Clinical Hematology, Casablanca, Morocco. Data from the medical records of 64 patients were collected over a period of 24 months. After induction therapy, the overall response (complete remission + very good partial response) was 67.2% (43 patients). The mean CD34-cell count in the autograft was 12.97*106 /kg [2.4- 53*106 Cd34+/kg] and the median length of hospitalization was 20.5 days [14-60 days]. The overall response after autograf was 84% (54 patients). At 24 months follow-up, overall survival (OS) was 83.5%, median OS was not reached and progression-free survival (PFS) was 65.9%, with a median PFS of 24.1 months with 95% confidence interval [21.7-26.5 months]. Autologous hematopoietic stem cell transplantation without cryopreservation is an excellent alternative in our context reducing wait times and freezing costs.

Congenital Alpha-2 Antiplasmin Deficiency: a Literature Survey and Analysis of 123 Cases.

BACKGROUND: Congenital alpha-2 antiplasmin deficiency is a rare, often misdiagnosed coagulopathy that may result in severe hemorrhage. Homozygous patients develop symptomatology in early childhood, while heterozygous individuals may be asymptomatic or bleed profusely following invasive dental procedures, surgery or trauma late in life. Due to the rarity of this entity, we performed an analysis of reported cases of congenital alpha-2 antiplasmin deficiency to share uncommon cases with the medical community, to raise awareness of the condition among clinicians, and to promote better patient management. METHODS: To identify relevant studies, PubMed and Science Direct were searched using controlled vocabulary and keywords based on medical subject headings (MeSH). Data of all reported cases of congenital alpha-2 antiplasmin deficiency were extracted and summarized for study setting, patient characteristics, and types of treatments. RESULTS: Thirty-three publications were identified encompassing one hundred twenty-three patients. This manuscript presents many important clinical conditions that are uncommon and may go undetected by medical personnel. It illustrates the importance of considering alpha-2 antiplasmin deficiency in the work-up of patients who present with a severe bleeding phenotype and may have normal coagulation screening tests. Management of such patients may be challenging especially when the diagnosis of alpha-2 antiplasmin deficiency is not known. CONCLUSIONS: Improved awareness and access to diagnostic tools will contribute to better management of rare co-agulopathies.

[Acute myeloid leukemia with inversion of chromosome 16: cytological, immunophenotypic and cytogenetic disruption]. / Leucémie aiguë myéloïde avec inversion du chromosome 16 : discordance cytologique, immunophénotypique et cytogénétique.

Acute myeloid leukemia (AML) with inv(16) is primarily associated with the eosinophilic LAM4 form belonging to the favorable prognosis group of AML. We report the case of an 18-year-old man with acute myeloid leukemia with unusual inversion of chromosome 16. Cytological, phenotypic and cytogenetic investigations showed a divergence from those in the literature. Indeed, the myelogram shows a medullary infiltration by elements blocked at the stage of myeloblates/promyelocytes, containing Auer rods grouped sometimes in fagots in blasts, promyelocytes and neutrophils. In view of this pathognomonic aspect, the diagnosis of AML type M3 is mentioned but quickly questioned by the results of immunophenotyping in favor of a maturing AML (M2). The karyotype and the FISH later objectify a recurrent anomaly "cytologically unexpected" inversion 16 (p13, q22) associated with trisomy 22.

[Analysis and management of the pre-analytical risks in hemostasis]. / Analyse et gestion des risques de la phase pré-analytique en hémostase.

Risk analysis consists in identification, scoring and ranking of risks in order to manage the major risks. The aim of the study is to determine the risk analysis of the pre-analytical step of routine hemostasis in Hematological laboratory of CHU Ibn Rochd-Casablanca, Morocco. MATERIAL AND METHODS: The identification of pre-analytical activities of routine hemostasis was extensively realized according to a "by-proccess" methodology. According to "5M" analysis, we identified the risks associated with these activities. Therefore, the scoring of each risk was realized according to «AMDEC¼ methodology, by the staff of hematological laboratory. Risks were classified according to their severity and the major were identified using "Pareto diagram". RESULTS: Forty eight risks were identified in 15 activities. Identity monitoring (13.7%), pre-analytical storage of samples (13.4%), pre-analytical treatment, including centrifugation (12.9%) and transport to the laboratory (11.3%) represented the activities that exhibited the highest level of risk. Using "Pareto diagram", we retained 19 major risks, related to medical prescription, identity monitoring, transport to the laboratory, pre-analytical treatment of samples and IT processing. DISCUSSION AND CONCLUSION: Risk analysis allowed the identification of 19 major risks out of 48 identified risks, related to the pre-analytical step of routine hemostasis. These 19 major risks needed a plan to reduce their criticity.

"Sickle cell trait and haemophilia: a rare association".

In this paper we analyze the combination of HbAS disease and haemophilia A must be exceedingly rare. Because of this rarity we report the case of two brothers with sickle cell trait and major haemophilia A. We conclude that it is about a post-circumcision bleeding due to major hemophilia A associated to sickle cell AS, this association was a systematic discovery.

Correlation between the plasma fibrinogen concentration and coronary heart disease severity in Moroccan patients with type 2 diabetes. Prospective study.

AIM: The present study aims at determining the relationship between the plasma fibrinogen concentration and the severity of coronary heart disease in type 2 diabetic patients. METHODS: Prospective analytical survey, based on a sample of 120 subjects divided in four groups: 30 non diabetic coronary patients (G1), 30 coronary diabetic patients (G2), 30 non-coronary diabetic patients (G3), and 30 healthy subjects (G4). RESULTS: The average age was 59.58±7.88 years; female gender predominated by 52.5%. The plasma fibrinogen concentration corresponded to 3.46g/L±0.86 in G1; 3.73g/L±1.11 in G2; 3.06g/L±0.98 in G3 and 2.46g/L±0.51 in G4; with a significant difference between the four groups (P=0.001). The plasma fibrinogen concentration increased in parallel with the cardiovascular risk (P=0.0001); there was also a significant correlation between the plasma fibrinogen concentration and the clinical and para-clinical coronary disease severity (respectively P=0.005 and P=0.0001). A positive correlation between the plasma fibrinogen concentration and hyperglycemia (P=0.035) was found in G4. But no correlation with the lipids parameters, except for the low density-lipoproteins in G3 (P=0.035). CONCLUSION: In the Moroccan population, the plasma fibrinogen concentration was positively and significantly correlated with the coronary heart disease severity.

Lead poisoning in children: a case report.

Lead colic is a rare cause of abdominal pain. The diagnosis of lead poisoning is most often mentioned in at risk populations (children, psychotic). We report the case of a 2 year old child that was presented for acute abdomen. Abdominal plain radiograph showed multiple intra-colonic metallic particles and suggested lead poisoning diagnosis. Anamnesis found a notion of pica and consumption of peeling paint. Elevated blood lead levels (BLL) confirmed the diagnosis. The lead poisoning is a public health problem especially in children, but its manifestation by a lead colic is rare and could simulate an acute abdomen table.

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.

Hematology reference intervals in Moroccan population.

BACKGROUND: Laboratory reference intervals are important for both clinical orientations and therapeutic decisions. In Morocco, no reference ranges are available for local population. The ranges commonly used in clinical laboratories and by physicians are those of Caucasian population. We have decided that it is relevant to undertake an epidemiological investigation on local adult healthy population, with the aim of establishing hematology reference intervals in Moroccan population. METHODS: Blood samples were taken from healthy adult volunteers of the regional transfusion center and measured on a Sysmex XE-2100 analyzer. We have grouped our data samples with regard to gender and retained donors aged between 18 and 45 years old according to ICSH guidelines 1982. Leucocyte, erythrocyte, and platelet parameters were analyzed. For any sample flagged by the automate or thrombopenia with platelets < 100000/microL, a systematic smear was done and checked. RESULTS: A significant difference between male and female was found with regard to the values for leucocyte, erythrocyte, and platelet parameters as well as for hemoglobin and hematocrit. These data were compared to normal values reported for Arabic, Caucasian, and African population. CONCLUSIONS: As part of this study, we have given a descriptive approach of normal blood cell count and its peculiarities in North African Arabian and Berber population not explored until now. We have established similarities and differences between our population and other African, Arab, and Caucasian populations.

Prevalence and risk factors of hepatitis B and C virus infections among the general population and blood donors in Morocco.

BACKGROUND: Viral hepatitis is a serious public health problem affecting billions of people globally. Limited information is available on this issue in Morocco. This cross-sectional study was undertaken with the aim of determining the seroprevalence and risk factors of hepatitis B virus (HBV) and hepatitis C virus (HCV) among the general population and among blood donors. METHODS: Blood samples from volunteers, have been screened with ELISA tests for detecting the hepatitis-B surface antigen (HBsAg) and anti-HCV. Within the seroreactive patients for HCV in the general population, RT-PCR was performed by the Cobas Ampliprep/Cobas Amplicor. RESULTS: HCV and HBV-seropositivity was documented in 1.58% and 1.81% out of 41269 and 23578 participants respectively from the general population. Two patients were found to be co-infected. HCV-RNA was detected by PCR in 70.9% of the 195 anti-HCV positive subjects. The anti-HCV prevalence was not different among males and females (P = 0.3). It increased with age; the highest prevalence was observed among subjects with >50 years old (3.12%). Various risk factors for acquiring HCV infection were identified; age, dental treatment, use of glass syringes and surgical history. In addition to these factors, gender and sexual risk behaviors were found to be associated with higher prevalence of hepatitis B. The HBV positivity was significantly higher among males than females participants in all age groups (P < 0.01). The peak was noticed among males aged 30-49 years (2.4%). None of the 152 persons younger than 20 years had HBsAg or anti-HCV. The prevalence of anti-HCV and HBsAg among 169605 blood donors was 0.62% and 0.96% respectively. CONCLUSIONS: Our study provided much important information concerning hepatitis B and C prevalence and risk factors; it confirmed the intermediate endemicity for HCV infection and pointed to a decreasing trend of HBV incidence, which might reclassify Morocco in low HBV endemicity area. This could be attributed primarily to the universal HBV vaccination among infants and healthcare workers over the past 13 years. HCV and HBV infections in the present survey were mainly associated with nosocomial exposures. Prevention and control of HBV infection are needed to reduce HBV transmission between adults.