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LEUKEMIA Dr MOKARIAN ICM 83/2/15. LEUKEMIA CLONAL DISORDER 8-10 /100.000 PATHOGENESIS: UNKNOWN. LEUKEMIA CHRONIC ACUTE CML CLL AML ALL - PowerPoint PPT Presentation
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LEUKEMIA
CLONAL DISORDER
8-10 /100.000
PATHOGENESIS: UNKNOWN
LEUKEMIA
CHRONIC ACUTE
CML CLL AML ALL
ADULT ADULT 90% OF ADULT 10% OF ADULT 10%OF CHILD 90%OF CHILD
LEUKEMIAAPPROUCH TO LEUKOCYTOSIS
MATURE MATURE IMMATURE IMMATURMYLOID LYMPHOID MYLOID LYMPHOID
LEUKEMOID CML AML ALLREACTION
LEUKOMOID RECTION CLL
LEUKEMIA
SYMPTOM & SIG
OF ANEMIA
OF THROMBOCYTOPENIA
OF LEUKOPENIA
OF BON MARROW EXPANTION
OF ORGAN DEPOSITION
OF INCREASED WBC
OF ELECTOROLITE DERANGMENT
LEUKEMIA
APROUCH TO LEKOCYTOSIS MIC METHOD
LIGHT MICROSCOPY IMMUNOHISTOCHEMISTRY CYTOGENETIC
FLOCYTOMETRY HISTOCHIMISTRY
AML ALL
PAS - +
MPO + -
SB + -
NSE + -
SE M4 M5
AB CHROMOSOME
CML Phi
ALL Phi
t(8-14)
AML T(15-17)
T(9-11)
CLL -
H history from patient with leukemia
Increasing fatigue or decreased exercise tolerance
(anemia)
Excess bleeding or bleeding from unusual sites (DIC,
thrombocytopenia)
Fevers or recurrent infections (granulocytopenia)
Headache, vision changes, nonfocal neurologic
abnormalities (CNS leukemia or bleed)
Early satiety (splenomegaly)
Family history of AML (Fanconi, Bloom or Kostmann
syndromes or ataxia telangiectasia)
History of cancer (exposure to alkylating agents,
radiation, topoisomerase II inhibitors)
Occupational exposures (radiation, benzene,
petroleum products, paint, smoking, pesticides
physical Examination
Performance status (prognostic factor)
Ecchymosis and oozing from IV sites (DIC, possible acute promyelocytic leukemia)
Fever and tachycardia (signs of infection)
Papilledema, retinal infiltrates, cranial nerve abnormalities (CNS leukemia)
Poor dentition, dental abscesses
Gum hypertrophy (leukemic infiltration)(M4)
Skin infiltration or nodules (leukemia infiltration)(M4)
Lymphadenopathy, splenomegaly, hepatosplenomegaly
Back pain, lower extremity weakness [spinal granulocytic sarcoma, most likely in t(8;21) patients]
PATHOGENESIS:
PHILADELPHIA CHROMOSOM
ABL / BCR GENE
THYROSIN KINASE
ETHIOLOGY : UNKNOWN
PRESENTATION
SYMPTOME
SIGN
PHASE OF DISEASE
CHRONIC PHASE
ACCELERATED PHASE
BLASTIC PHASE
DIAGNOSIS
TREATMENT :
HYDROXYURAE
INTERFERON
BONE MARROWWWW TRANSPLANTATION
GLIVEC
SUPORTIVE CARE
CML
CLINICAL FINDING
ASYMPTOMATIC 40%SYMPTOMATIC FATIGUE BLEEDIN TENDENCY ILLBEING F8 DEF FEVER VWF DEF LAP THROMBOCYTOPENIA HEPATOSPLENOMEGALLY AUTOIMMUN MANIFISTATION STERNANAL TENDERNESS ABDOMINAL MASS SKIN INFILTERATION INFILTERATION OF TONSILS INFILTERATION OF ORGAN
INTERNATIONAL CLL WORKSHOP DIAGNOSTIC CRITERIA:
1- LYM> = 10000 2-BMA LYM > = 30% A= 1 + 2 OR 3 3- MONOCLONAL B- CELL B= 2+3NCI-SPONSORED CLL WORKING GROUPED 1- LYM> 5000 + LESS 55% ATYPICAL LYM + B-CELL MARKER + CD5 ( CD19 CD20 CD24 ) 2- MARROW LYM>30%
DIFFERENTIAL DIAGNOSIS: INFECTION CAUSES MALIGNANT CAUSES BACTERIAL ( eg TB) B CELL VIRAL ( IM) PLL HYPERREACTIVE MALARIA NHL SPLENOMEG(HMS) HCL T CEL PLL NHL HCL LGL L
PRETREATMEN INVESTIGATION
CBC PBS RET COOMB’S TEST LDH LFT KFT SPEP IEP B2 MICROGLOBULIN IMMUNOPHENOTYPING BMA CYTOGENETIC ANALYSIS
RAI CLASSIFICATION
STAGE MODIF STAGE DESCRIPTION MS (YR)
0 LOW RISK LYM >10 1 INTERMED RISK LYM+ LAP >8 2 INTERMED RISK LYM + SPL+/-LAP 6 3 HIGH RISK LYM +ANEM+/- LAP OR SPL 2 4 HIGH RISK LYM +THROM 2 +/- ANEM +/- SPL +/- LAP
LYM > 5000 >4WEAK HB<11 PLT< 100000
BINET CLASSIFICATION FOR CLL INVOLVED MS SRAGE BLOOD COUNTS AREA (YRS)
A HB>10 <3 >10 PLT>100000B HB>10 >3 7 PLT>100000C HB<10 ANY NUMBER 2 PLT< 100000
FIVE AREA OF INVOLVEMENT:H&N AXILLA GROINS SPLEEN HEPATOMEG
SUMMARY OF TREATMENT: INDICATION OF CCR CHLORAMBUCIL OR FLUDARABIN PREDNISOLON RADIOTHERAPY SPLENECTOMY GAMMAGLOBULIN
MARKERS OF POOR PROGNOSIS IN CLL:
ADVANCE STAGE DOUBLING TIME <12 M DIF MARROW INVOL PROLYM OR CLEAVED CELL INCREASED POOR RESPONSE TO CCR HIGH B2 MG LEVEL ABNORMAL CARYOTYPE P53 MUTATION
CLL
CLASIFICATION
LEUKOSTASIS
DIAGNOSIS
TREATMENT
SUPORTIVE CARE
CHEMOERAPY
INDUCTION OF REMMISION
CONSULIDATION
MAINTENANCE
Acute Myeloid Leukemia (AML) Classification Systems
French-American-British (FAB)
ClassificationM0: Minimally differentiated leukemia
M1: Myeloblastic leukemia without maturation
M2: Myeloblastic leukemia with maturation
M3: Hypergranular promyelocytic leukemia
M4Eo: Variant: Increase in abnormal marrow eosinophils
M4: Myelomonocytic leukemia
M5: Monocytic leukemia
M6: Erythroleukemia (DiGuglielmo's disease)
M7: Megakaryoblastic leukemia
World Health Organization ClassificationbI. AML with recurrent cytogenetic translocationsAML with t(8;21)(q22;q22);AML1(CBFa)/ETOAcute promyelocytic leukemia [AML with t(15;17)(q22;q12) and variants; PML/RARa]AML with abnormal bone marrow eosinophils [inv(16)(p13q22) or t(16;16)(p13;q22) CBFb/MYH1]AML with 11q23 (MLL) abnormalitiesII. AML with multilineage dysplasiaWith prior myelodysplastic syndromeWithout prior myelodysplastic syndromeIII. AML and myelodysplastic syndrome, therapy-relatedAlkylating agent-relatedEpipodophyllotoxin-relatedOther typesIV. AML not otherwise categorizedAML minimally differentiatedAML without maturationAML with maturation
AML
AML AUER ROD
CLASIFICATION
LEUKOSTASIS
DIAGNOSIS
TREATMENT
SUPORTIVE CARE
CHEMOERAPY
INDUCTION OF REMMISION
CONSULIDATION
MAINTENANCE
ALL
Classification of Acute Lymphoid Leukemia (ALL)
ImmunologicSubtype
% of Cases FAB Subtype Cytogenetic Abnormalities
Pre-B ALLT cell ALLB cell ALL
75205
L1, L2L1, L2L3
t(9;22), t(4;11), t(1;19)14q11 or 7q34t(8;14), t(8;22), t(2;8)
NOTE: FAB, French-American-British classification.