Cytogenetic and Genetic Advances in Myelodysplasia Syndromes

Myelodysplasia syndromes (MDS) are defined by a heterogeneous group of myeloid malignancies characterized by peripheral blood cytopenia and dishematopoiesis and frequently progress to acute myeloid leukemia. Conventional karyotype has a crucial role in myelodysplastic syndrome (MDS) and is one of items of the International Prognostic Scoring System (IPSS) for patient risk stratification and treatment selection. Approximately 50–60% of cases of MDS present chromosomal abnormalities, like the deletions of chromosome 5q and 7q, trisomy 8, and complex karyotypes. New genomic technologies have been developted, like single-nucleotide polymorphism array and next-generation sequencing. They can identify the heterozygous deletions wich result in haplo-insufficient gene expression (e.g., CSNK1A1, DDX41 on chromosome 5, CUX1, LUC7L2, EZH2 on chromosome 7) involved in the pathogenesis of myelodysplasia syndromes. Genetic abnormalities are multiple, the most recurrent one are involved in the RNA splicing like SF3B1, SRSF2, U2AF1, ZRSR2, LUC7L2, and DDX41. Epigenetic modifications are also identified, such as histone modification as ASXL1, EZH2. Finally, it can be DNA methylation (e.g., TET2, DNMT3A, IDH1/IDH2). On this review we will summarize the most recent progress in molecular pathogenesis of MDS, and try to better understand the pathogenesis of the specific subgroups of MDS patients and applications of discovery of new genetic mutation in the development of new therapeutic

Haematological Malignancies: Overview of the Recent Progresses in Genetics

Genetic defects play a major role in pathogenesis of the most of haematological malignancies, including cytogenetic abnormalities, gene mutations, and abnormal gene expression. Our knowledge about the genetics of haematological disorders has been dramatically improved during the past decade, due to revolution of sequencing technologies which have played a crucial role. In this chapter, we describe the techniques commonly employed for elucidating chromosomal aberrations, prognostic impact of recurrent chromosomal abnormalities, and recently updated risk stratification systems. We will summarise the chromosomal abnormalities recently identified on many of haematological diseases such acute myeloid leukaemia, acute lymphoid leukaemia, myelodysplasic syndrome, multiple myeloma, meyloproliferative disease and clarify their impacts on clinical phenotype and prognosis, as well as their role in the pathogenesis of these diseases. The aim of this chapter is to provide a brief overview of the recent progresses in haematological diseases genetics

Genetic Abnormalities in ALL

Acute lymphoblastic leukemia (ALL), can be defined by a family of genetically heterogeneous lymphoid neoplasms derived from B- and T-lymphoid progenitors. ALL constitutes the most common childhood cancer, due to an overproduction of immature lymphoid hematopoietic cells. Genetic analyzes currently provides important information for classifying patients into prognostic groups, genetic analysis also helps to understand the mechanisms of relapse, pharmacogenetics and the development of new potential therapeutic targets, which should help to further improve the results of leukemia. In fact, the new techniques in molecular cytogenetic permits to identify new cryptic abnormalities, these discoveries have led to the development of new therapeutic protocols. The role of cytogenetic analysis is crucial on ALL patient’s management. Karyotyping coupled with FISH analysis identifies recurrent chromosomal abnormalities in ALL, many of these abnormalities have prognostic and treatment impact. This chapter summarizes chromosomal abnormalities that are common and classify ALL according to the World Health Organization (WHO) classifications (2016 revision). We will present the main genetic modifications recently identified as well as the sequence mutations which have helped in the elucidation of the pathogenesis of ALL

Ostéonécrose Cortico-induite Multifocale au Cours d’une Leucémie Aigue Lymphoblastique: A Propos d’un Cas

Les corticostéroïdes oraux sont couramment utilisés en hématologie, en particulier dans le traitement des leucémies aiguës et des lymphomes. L'ostéonécrose est une complication significative et invalidante de la corticothérapie. Les patients du service d’hématologie reçoivent des thérapies combinées à base de chimiothérapies et de corticoïdes. Ils sont ainsi à risque élevé de développer une ostéonécrose avasculaire, qui est malheureusement le plus souvent diagnostiquer aux stades avancés de la maladie. Par conséquent, les cliniciens doivent être conscients du potentiel risque de cette complication et de l’importance d’un diagnostic précoce et d’un traitement adéquat afin d’améliorer le pronostic fonctionnel de ces patients qui ont survécu à leur maladie cancéreuse. Nous rapportons le cas d’un jeune adulte atteint de leucémie lymphoblastique aiguë, traité par une combinaison de corticoïdes et de chimiothérapie, compliquée d’une ostéonécrose multifocale, et discutons brièvement cette complication rare mais redoutable à la lumière de la littérature existante. Osteonecrosis is recognized as one of the most common therapyrelated side effect in patients with acute lymphoblastic leukemia. Long continuous use of corticosteroid during all therapy is the major contributor to the development of osteonecrosis. To reduce osteonecrosis which is associated with debilitating long-term effects, steroid prescription should be rational. Patients should be diagnosed in early asymptomatic stages of osteonecrosis by MRI to improve prediction, management, and to prevent functional impairment. This paper focuses on reporting a case of a young adult treated with a combination of high dose corticosteroids and multi-agent chemotherapy for acute lymphoblastic leukemia. It was complicated by development of a multifocal osteonecrosis. This rare but serious complication was also briefly discussed in light of the existing literature

Current Cytogenetic Abnormalities in Acute Myeloid Leukemia

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

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

Pain Management in Children with Cancer: National Surveys of Practices and Perceptions in Morocco

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

Assessment of oral health-related quality of life among children with acute leukemia

Aim: To assess the impact of oral health on the quality of life in children with acute leukemia.Methods: Forty children (age 11 to 14 years) with acute leukemia from the Pediatric Oncology and Hematology Departments of the 20th August Hospital Casablanca and the Pediatrics Department P3 at Abderrahim Harouchi Hospital Casablanca, Morocco were surveyed. Data was collected via an administered questionnaire. The questionnaire is a translated version of the Child-Oral Impacts of Daily Performance Questionnaire in Arabic (validated in Morocco).Results: The most commonly reported problems were: dental tartar, teeth position abnomalities, tooth decay, dental sensitivity and oral ulcerations. The overall prevalence of oral problems impacting upon daily activities (eating, speaking, cleaning teeth, relaxing, sleeping, smiling, showing teeth, studying and being in touch with other children) over the last 3 months was 52.5%. The most frequently affected daily activity was eating difficulties (45%) while the most frequently reported problem was oral ulcerations.Conclusion: Studies have confirmed that children over the age of 11 are able to perceive their general and oral health as well as its impact on their daily lives. The current study showed that oral problems on top of general health complications among children with acute leukemia lead to a deterioration in their quality of life, which is already affected by malignancy and chemotherapy.Improving awareness on the importance of oral health-related quality of life among children with acute leukemia would be valuable

AMYLOSE CONJONCTIVALE: PREMIERE MANIFESTATION D’UNE AMYLOSE SYSTEMIQUE ASSOCIEE AU MYELOME MULTIPLE

IntroductionL’amylose systémique de type AL a été décrite dans presque tous les organes. Cependant l’atteinte conjonctivale est relativement rare et décrite le plus souvent sous forme de cas isolés et petites séries de cas. Elle est le plus souvent une manifestation de l’amylose oculaire localisée; toutefois, une atteinte palpébrale peut survenir dans le cadre d’une forme systémique. Nous rapportons l’observation d’une amylose AL, qui apparait originale par l’atteinte conjonctivale révélatrice en soulignant le retard diagnostic et thérapeutique du à la méconnaissance de cette localisation et les tentatives de traitement symptomatique.ObservationUn patient de 58 ans présentait un purpura palpébral, périorbitaire bilatéral en lunette et des masses conjonctivales avec notion d’hémorragies conjonctivales intermittentes. Cette symptomatologie évoluait depuis plus de 12 mois, ayant suscitée plusieurs consultations ophtalmologiques et dermatologiques, ainsi que divers traitements symptomatiques jusqu’à réalisation d’un bilan biologique objectivant un pic des gammaglobulines à l’électrophorèse des protéines sériques suivi de la réalisation d’une biopsie conjonctivale posant le diagnostic d’amylose et imposant une recherche extensive ayant retrouver d’autres localisations d’amylose associées au myélome multiple.Discussion/ Conclusion  L’amylose  conjonctivale est une affection rare, dont le diagnostic est suspecté cliniquement et confirmé par examen histopathologique. Elle peut être le seul signe révélateur d’une atteinte systémique et son diagnostic impose une recherche systémique d’autres localisations