Charles Mxxx DCEM2 Toulouse Purpan Medical School 01/26/2012 ECN Item 162
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1 Charles Mxxx DCEM2 Toulouse Purpan Medical School 01/26/2012 ECN Item 162
2 Definition Pathophysiology Clinical signs and symptoms Biology and Diagnosis Different types of AL Prognosis and Treatment
3 Malignant Hemopathy: cancer - Accumulation of blasts in the bone marrow - Affects the production of normal blood cell ( ) - Rapid evolution without TTT Chronic leukemia: - production - slow evolution Rare disease: 4-5/100,000/year 2 main types - Acute Myelogenous Leukemia (age++) - Acute Lymphoblastic Leukemia: 1/3 of children K + several subtypes
4 Mutagenic event Successive mutations (many genes involved) Leukemic phenotype Maturational arrest of bone marrow cells Early stages of development = Clonal proliferation of immature cells 1. Accumulation of immature cells in the bone marrow (+/-other organs) 2. Decreased production of normal blood cells Etiological Factors: - Mostly unknown -Hematological disorder: myelodisplastic syndrome ++ -Chemotherapeutic agents: alkylating agents, topoisomerase II inhibitors - Genetic factors: Trisomy 21, Fanconi disease, Li-Fraumeni syndrom, - Environmental exposures: ionizing radiations, benzene
5 VARIABLE UNSPECIFIC: ORIENTATION ++ Signs of medullar insufficiency - Anemic syndrome (asthenia, paleness, dizziness, ) -Haemorrhagic syndrome (bleeding gums, ecchymoses) - +/- Infectious signs (fever++): located infection septicemia Tumoral syndrome: infiltration by leukemic cells - Adenopathies - Hepato-Splenomegaly -Visceral localisations: gums, bones, skin, testicles,... - If WBC>100,000 cells/ul = leukostasis = clump of leukocytes in pulmonary or brain capillaries (ARD, coma, convulsions emergency)
6 Diagnosis: Based on biological results Complete Blood Count: -Aregenerative Anemia ++ - Thrombocytopenia - Neutropenia - Leukocytopenia vs. Hyperleukocytosis - +/- Blasts (myeloid or lymphoid) Bone marrow Aspiration: - Rich marrow - >20% Blasts - normal cells Complementary studies: -morphological studies -immunophenotyping ESSENTIAL TO - cytochemistry investigations (MPO reaction) CLASSIFY -cytogenetic studies: karyotype (prognosis++) THE - molecular evaluation of BW DISEASE
7 FURTHER INVESTIGATIONS o Clotting studies: Disseminated Intravascular Coagulation (AML3++) - Prothrombin time - fibrinogen level - fibrin split product Blood electrolytes profile: LDH, Uric acid, K+, Ca++ (tumor lysis syndrome) o o Lumbar Puncture: systematic (brain localization?) o o Chest X-ray: pneumopathy, leukostasis +/- Fever: Blood culture, urine culture o +/- Pre-transfusion procedures = blood group, serologies (HIV, HBV, HCV, CMV)
8 Classification Acute Myeloid Leukemia (AML) FAB: morphology, degree of differenciation of blasts (LAM 0 to LAM 7 ) OMS: Clinical, morphological & cytogenetic characteristics Acute Lymphoblastic Leukemia (ALL) preb-cell ALL (>85%) pret-cell ALL (10-15%) Cytology Myeloblasts: - big size - granulations -Auer rods Lymphoblasts: -small size - shape: rounded cells - reduced cytoplasm Cytochemistry MPO positive MPO negative Immunophenotyping Myeloid markers (CD13, CD33, ) Lymphoid markers
9 Gravity Signs Thrombocytopenia / Bleedings Septic shock / Fever Agranulocytosis + Fever Leukostasis (Oncologic ER) Tumor lysis syndrome Anemia (Hb<8g/dL) Symptomatic Treatment Platelets Transfusions ATB +/- Intensive care IV ATB with broad spectrum Chemotherapy/ Leukopheresis Hydratation, Alcalinisation, Red blood cells Transfusions
10 Objectives of Treatment: - Complete Remission (<5% blasts in BW, normalization of CBC) - Maintain the complete Remission - Avoid relapses 1) Induction therapy: INTENSIVE CHEMOTHERAPY = of leukemic cells - 1 month - AML: anthracyclins + arabinosylcytosine - ALL: anthracyclins, vincristin, prednisone, cyclophosphamide. Induced aplasia 2) Consolidation therapy: Maintain complete remission - chemotherapy (several months) +/- allogeneic HSCT: efficient to avoid relapses ALL: children, only if bad prognosis AML: age <60 (sepsis, toxicity++) +/- autologous HSCT *HSCT = of relapse rate, of 6-year survival rate in patients younger than 50
11 Some cases: supportive chemotherapy (2 years): children ALL if no HSCT, APL 3) Supportive care: Heavy treatment -«Hematologic resuscitation»: transfusions support anti-infectious care (isolation, ATB) - nutritional supplements - staff: experience ++ in treatment of leukemias 4) New treatments: Advanced knowledges on the pathophysiology of AL = New treatment perspectives arrest -Azacitidine (VIDAZA): DNA hypomethylation * no AMM in this indication: trial in process - Monoclonal Antibodies: new targets -Histone Deacetylase Inhibitors: «Ras»inactivation = cell growth
12 Accumulation of blasts in the bone marrow production of normal blood cells Tumoral syndrom CLINIC: ONLY ORIENTATION Medullar Insuffisiency Bone Marrow Aspiration: > 20% blasts CBC results: always abnormal Heavy Treatment: Etiological, treatment of gravity signs, supportive care
13 Livre du Collège National des Enseignants d Hématologie Livre du Collège National des Enseignants en Médecine Interne (éd.ellipses) Dictionnaire Médical, 5 ème édition (éd. MASSON)
Group of malignant disorders of the hematopoietic tissues characteristically associated with increased numbers of white cells in the bone marrow and
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