leukemia dr mokarian icm 83/2/15

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.