ACUTE LEUKEMIA_1_

ACUTE LEUKEMIA Dr.Huda al abd alkarim Assistant prof& consultant oncologist DEFINITION : Clonal malignant disorders characterized :by the proliferation of abnormal (leukemia)Blast cells and impaired production of normal blood cells. Lymphoblast/myeloblast EPIDEMIOLOGY :     Incidence: 5% of all new cancer cases. AML common in adult ALL most common in children Etiology: – Ionizing radiation. – Benzene. – Chemotheraputic agent(alkylating agent,topoisomerase II inhibitor) – Human T-lymphocyte leukemia virus (HTLV1). – Congenital disorder:  Down syndrome.  Immunodeficiency syndrome. Clinical presentation:  Will present with sign or symptoms related to : – Pancytopenia:  WBCinfection.  Hb anemia.  platelets bleeding. – Organ infiltration:  Lymphadenopathy. More common with ALL than AML.  Splenomegally.  Hepatomegally.  CNS:5-10% of patient with ALL Investigations:  CBC: – – – – – – –  electrolytes: 60% of pts have an elevated WBC. Most are anemic Most are thrombocytopenic 90%have blast in the periphral blood film. Hypo/hyper kalemia Hypomagnesimia hyperphosphatemia  Hypermetabolism: DIC: – – – – – – LDH. uric acid.    Bone marrow biopsy and aspirate: Radiology: 30%or more of all nucleated cells are blast. Most common with promyelocytic leukemia,small% monocytic leukemia&ALL CXR:mediastinal mass(T-cell ALL) Osteopenia or lytic lesion 50% of patients with ALL.(itractable pain). CLASSIFICATION  Criteria: - Morphology :apperance of cell under microscope. -Cytochemistry:chemical activity of the cell.(myeloperoxidase , Sudan Black B) -immunophenotyping: antigen pressent in the cell membrane - Cytogenetics: chromosome of the cell - Molecular biology:  Classification: 3 groups of acute leukemias: - acute myeloid leukemias AML(M1 –M6). - acute lymphoblastic leukemias ALL (L1-L3). - Biphenotypic leukemias or Acute undifferentiated leukemia Differential diagnosis of Acute leukemias:  Lymphoma.  Myelodysplastic syndrome.  Multiple myeloma.  Aplastic anemia  Sever megaloblastic anemia due to B12 defeciency.  Severe lymphocytosis due to infections. Management:  A-Supportive measure: -isolation in positive laminer flux room -insertion of central line -family and patient support by permanent social worker -AlKaline diuresis to prevent tumor lysis syndrome -oropharynx/GIT decontamination to prevent fungal infection -IV antibiotics for infection -Blood transfusion if anemia and thrombocytopenia. Therapeutic option  B-Curative intent: only allogenic bone marrow transplant .  C_Classical approch(curative/palliative) -induction chemotherapy -consolidation of remission -intensification -maintenance chemotherapy -CNS prophylaxis Cont:  Special consideration: by intrathecal chemotherapy,high dose systemic MTX or Aracytine. OR cerebrospinal irradiation CNS: -neuroprophylaxis: - meningeal infiltration: Testis: orchidectomy/radiotherapy if testis involvement. Prognosis in ALL parameters WBC Gender Immunophenotype Age Cytogenetic Good low Girls C-ALL Child Normal,hyperdiploid, poor High(>50x10 9 /l) Boys B-ALL Adult or infant. Ph+,11q23rearrangements. Time to clear blast from blood Time to remission Cns disease at presentation Minimal residual disease < 1week <4weeks Absent Negative at 1-3 months >1week >4weeks Present Still positive at 3-6 months. . Prognosis in AML parameters Cytogentics Favorable T(15;17). T(8;21). Inv(16). unfavorable Deletion of chromosome5or7. 11q23 T(6;9) Abn(3q)complex rearrangments >20% blasts after first course. BM response to remission induction <5% blasts after first course age <60yrs >60yrs