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ACUTE Leukemia

ACUTE Lymphocytic Leukemia

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ACUTE Leukemia

ACUTE LeukemiaWhat Is Leukemia?Cancer of the white blood cellsAcute or ChronicAffects ability to produce normal blood cellsBone marrow makes abnormally large number of immature white blood cells called blastsHistoryMeans white blood in GreekDiscovered by Dr. Alfred Velpeau in France, 1827Named by pathologist Rudolf Virchow in Germany, 1845Main TypesAcute Lymphocytic Leukemia (ALL)Acute Mylogenous Leukemia (AML)Chronic Lymphocytic Leukemia (CLL)Chronic Mylogenous Leukemia (CML)

18/04/20165Classification of LeukaemiaAcuteChronic

MyeloidLymphoid

5Demographics of Leukemia Patients (2001 Data)

Total Reported Cases = 31,500Sources from Leukemia, Lyphoma, Myeloma Facts 2001CLL=Chronic LymphocyticALL=Acute LymphocyticCML=Chronic MylogenousAML=Acute MylogenousSymptomsWhen there are excessive white blood cells --> InfectionsWhen there are few red blood cells: Paleness --> AnemiaWhen there are few platelets --> Excessive bleedingTests For DiagnosisFinger prickBlood sampleBlood dyeBone marrow sampleSpinal Tap/Lumbar PuncturePictures Of Blood

Normal human bloodWhite CellRed CellPlatelet

Blood with leukemiaBlastsRed CellPlateletWhite CellSources from Arginine.umdnj.eduSources from beyond2000.comEffects On the BodyAttacks the immune systemInfectionsAnemiaWeaknessNo more regular white blood cells, red blood cells, and plateletsBlasts clog blood stream and bone marrowDevelopment of Leukemia in the BloodstreamStage 1- NormalStage 2- SymptomsStage 3- DiagnosisStage 4- WorseningStage 5a- AnemiaStage 5b- InfectionLegend White Cell Red Cell Platelet Blast GermSources from Leukemia, by D. Newton and D. SiegelCausesHigh level radiation/toxin exposureVirusesGenesChemicalsMostly unknownTreatmentChemotherapyImmunotherapyRadiationBone marrow transplantACUTE LEUKAEMIA18/04/201615Rapidly progressiveProliferation of primitive blast cellsAcute myeloblastic (myeloid) leukaemiaAcute non-lymphoblastic leukaemiaAcute lymphoblastic leukaemia15CLINICAL PRESENTATIONSymptoms of acute leukaemia are largely the result of interference with normal haematopoiesis.Generally it is not possible on clinical presentation to differentiate lymphoid from myeloid leukaemia. Causes of Acute LeukemiasIdiopathic (most)underlying hematologic disorderschemicals, drugsionizing radiationviruses (Human T Lymphotropic Virus I)hereditary/genetic conditionsPreceding bone marrow disordersChemotherapy especially alkylating agents, epipodophyllotoxins and anthracyclines

17CLINICAL SIGNSpallorlymphadenopathyhepatosplenomegalysternal tendernesspurpura / petechiaeretinal haemorrhagesmouth ulcersgum hypertrophy (monocytic type) LABORATORY FINDINGSHb is invariably low (30-80 g/L)WBC is usually high (especially lymphoblastics and monocytics). Can be normal or low.Pltsusually dangerously lowGenerally it is not possible to differentiate myeloblasts from lymphoblasts by morphology alone.MANAGEMENTCytotoxic chemotherapy, radiotherapy and bone marrow transplantation. The goal is to eradicate the leukaemic cell mass while giving supportive care. In children with ALL postremission therapy includes central nervous system (CNS) prophylaxis.PROGNOSISYoung patients do better than old. Patients presenting with low white counts do better. Must achieve complete remission (no signs of leukaemia and return of normal haematology parameters) to prolong survival. 18/04/201621Acute Lymphoblastic LeukaemiaWHO classification:Precursor B cell ALLPrecursor T cell ALLBurkitts mature B lymphoblastic leukaemia/lymphomaBi-phenotypic leukaemiaFABL1, L2, L318/04/201622Epidemiology of ALLPeak incidence in children aged 4 yearsRising incidence in old age

18/04/201623Prognostic factors in ALLSex: female > maleEthnicity: caucasian > non-caucasianAge: 1 year oldWBC < 50 x 109/lCNS involvement is badInitial response to treatment (day 14 BM)Morphological and genetic sub-typesClinical features of ALLBone pain childrenCNS involvementLymphadenopathy

ContinueInvolvement of other tissue such as spleen, liver, lymph node, and meninges are commonInvolvment of CNS may give rise to headach, vomiting and irritable behaviour.Principles of Treatmentcombination chemotherapyfirst goal is complete remissionfurther Rx to prevent relapsesupportive medical caretransfusions, antibiotics, nutrition, metabolic /electrolyte abnormalitiespsychosocial supportpatient and family26Therapeutic Concepts in ALLInduce a complete remission and restore normal hematopoiesis avoiding excessive toxicityReduce inapparent leukemia with short-term, high-dosage cytocidal therapy early in remission when the child is well and drug sensitivity is greatest Prevent CNS leukemiaUse prolonged combination chemotherapy to eradicate residual disease when there is no evidence of leukemia

Basic Therapy in Childhood ALLInduction Treatment 4-8 wkConsolidation treatment (intensification) 2-10 wkContinuation treatment (maintenance) 2-3 yReinduction therapy (delayed intensification) 2-7 wkCNS-directed therapy (intrathecal injection of methotrexate and cranial radiation) 3 wkChart3350081001000047005200

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