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.

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.

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.

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.