Leukemia

Tinny Rasjad

WBC Maturation

Hemopoietic Stem Cell (HSC)

HSCs proliferate continuously. Two kinds HSC for leukocyte: 1. Myeloid cell 2. Lymphoid cell

Fetus to 6-7 months old: Myeloid and lymphoid system (especially produced in lever and spleen)

Post natal (6 monthadult): Myeloid and lymphoid system are produced in bone marrow

What Is Leukemia?

Cancer of the white blood cells Acute or Chronic Affects ability to produce normal blood cells Bone marrow produce abnormal large number of immature white blood cells called blasts

DISCRIPTION:

Unknown etiologic disease Characterized:

Uncontrolled, abnormal, widespread proliferation white blood cell Bone marrow & other body tissue infiltration Accompanied by immature & abnormal leucocyte appearance in the peripheral blood In some cases: there are an abnormal red cell & megakaryocyte proliferation

History

Means white blood in Greek

Discovered by Dr. Alfred Velpeau in France, 1827 Named by pathologist Rudolf Virchow in Germany, 1845

LEUKEMIA CLASSIFICATION
AM L ( ANLL )

ACUT ACUTE

ALL ALL

LEUKEMIA

CML

CHRONIC

CLL

CLASSIFICATION:
Depend on the number of predominant cells
ACUTE LEUKEMIA: Immature cell ( BLAST ) > Mature cell CHRONIC LEUKEMI: Mature cell > Immature cell (Blast )

Demographics of Leukemia Patients (2001 Data)

CLL=Chronic Lymphocytic ALL=Acute Lymphocytic CML=Chronic Mylogenous AML=Acute Mylogenous
CML 15% CLL 26% others 17% ALL 11%

AML 31%

Sources from Leukemia, Lyphoma, Myeloma Facts 2001

Total Reported Cases = 31,500

Symptoms

When there are excessive abnormal white blood cells --> Infections When there are few red blood cells: Paleness --> Anemia When there are few platelets --> Excessive bleeding

Tests For Diagnosis

Blood sample

Blood smear
Bone marrow sample Spinal Tap / Lumbar Puncture

CYTOCHEMISTRY

MYELOPEROXIDASE (MPO)FOR MYELOID SERIES SUDAN BLACK to know fat particle in granulocyte & monocyte ESTERASE SPECIFICfor monocyte TdT ( terminal deoxy nucleotidyl transferase) increase in ALL

PAS to know glycogen

in lymphoblast

Pictures of Blood Smear

Platelet White Cell Red Cell White Cell Red Cell Platelet Blasts

Normal human blood

Sources from Arginine.umdnj.edu

Blood with leukemia

Sources from beyond2000.com

Effects on the Body

Attacks the immune system Infections Anemia, neutropeni, thrombocytopeni Weakness Infiltration leukemic cell to organs & tissue Gums,bone, CNS, lever, ovarium Increase basic metabolic rate caused by mass Sweating, decrease body weight

Development of Leukemia in the Bloodstream

Stage 1- Normal

Stage 2- Symptoms

Stage 3- Diagnosis

Legend

White Cell Red Cell Platelet Blast Germ

Stage 5a- Anemia

Stage 4- Worsening
Sources from Leukemia, by D. Newton and D. Siegel

Stage 5b- Infection

Causes

High level radiation / toxin exposure

Viruses Genes Chemicals Mostly unknown

Treatment

Chemotherapy

Immunotherapy
Radiation Bone marrow transplant

ALL
(ACUT LYMPHOBLASTIC LEUKEMIA)

Most common in children

Acute Lymphoblastic Leukemia

Proliferation of lymphoblasts
anemia, thrombocytopenia, increased WBC Lymphadenopathy / splenomegaly

B or T-cell

flow cytometry

TdT (terminal deoxy nucleotidyl transferase) (+) Most common leukemia of childhood

sign - ALL
( ORGAN INFILTRATION )

Anemia and fever Bone pain Superficial lymphadenopaty Meningeal Syndrome Hepato splenomegaly Testis enlargement

ALL diagnosis

Pheriferal blood ( WRIGHT)

leukocytosis. lymphoblast >> Anemia Trombocytopenia.

Bone marrow HYPERPLASTIC. ( normal cells insisted by lymphoblast ) CYTOKIMIA

PAS ( +) (PERIODIC ACID SCHIFF) TdT (terminal deoxynucletidil transferase) Chromosome defect, subtype, tx responded prognose

CYTOGENETIC.

IMUNO PHENOTYPING.

Acute Lymphoblastic Leukemia

Differential diagnosis of ALL

1.

Mononucleosis infectiosa

Atypical lymphocyte >> (not immature cells) Not anemia , not thrombocytopenia

2.

AML

AML
ACUT MYELOBLASTIC LEUKEMIA (ANLL=Acut Non Lymphocytic Leukemia) more common in adult

CLASSIF - AML = ANLL ( Acut Non Lym Leu)

AML APL
M0, M1,M2

M3

AMMOL
FAB ( A N LL)

M4

AMOL
EL

M5

M6

MEGA

M7

Acute Myelogenous Leukemia

Proliferation of myeloblasts anemia, thrombocytopenia, increased WBC Increase WBC in perifferal blood and Bone marrow Infiltration to gums and oral mucous (M4-M5) Myeloid, monocytic, RBC, or megakaryocytic flow cytometry myeloperoxidase +, TdTAuer rod (+) Over age of 20

Acute Myelocytic Leukemia

Problem

Difficult to distinguish between ALL and ANLL The same therapy for M0 M7, but different therapy and prognosis for ALL

Myeloid Cells

In Acute Leukemia
Inhibition blast maturation Accumulate in bone marrow. Impair another normal bone marrow function

In Chronic Leukemia
The cells tend out of bone marrow and accumulate in extra-medullary (lien and lymphoid gland) Longer bone marrow failure

DIAGNOSIS :
( CLINIC & LABORATORY)

CLINIC :

Fever Anemia Bleeding Hypermetabolism Hepato-splenomegaly

LABORATORY AML
Perifferal blood:

LEKOSITOSIS :

Especially ( MYELOBLAST) MONOTON

GRANULOPOESIS disturbance NETROPENIA ( HYPOGRANULER) AUER ROD (+) HIATUS LEUKEMICUS NORMOBLAST (+) RETICULOCYTOPENIA (bone marrow damage )

ANEMIA (NN)

TROMBOCYITOPENIA DIC (Specially APL)

BONE MARROW
Blast -Hyperplasia > 30% ( Gran system ) pressure surrounding system Auer Rod positive (pathognomonis = Characteristic (M3,M4,M5 )

HIATUS LEUKEMICUS positive.

hyperuricemia. Increase lysozyme ATN (M4-M5)

HIATUS LEUCEMIKUS
n
blast blast blast blast AML

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 ACUT MYELOBLASTIC LEUCEMIA = M0 (minimally differentiated) Bone marrow Blast > 30% without granules ACUT MYELOBLASTIC LEUCEMIA = M1 (without maturation) Bone marrow Blast > 30 % with / without granules Maximal maturation 10 %

ACUT MYELOBLASTIC LEUCEMIA = M2 (with maturation)

Blast > 30 % Mature cell ( promyelosit) > 10% but < 30 %

M3 ACUT PROMYELOCYTIC LEUKEMIA

More 30 % myeloblast & promyelocyte Coarse cytoplasmic granules (thromboplastin like substance) DIC Anemia Thrombocytopenia DIC Gums bleeding Auer rod ( + ) Peroxydase & Sudan black (+)

M-4 ACUT MYELO MONOCYTIC LEUKEMIA

Blast > 30 % (Mono blast > 20 %, myeloblast > 30%) There are monosit & pro monosit DD: M-5 peroxidase test M5 (negative)

M-5
( ACUT MONOCYTIC LEUKEMIA )

BLAST > 30 %
(blast, monocyt >>, promonocyt >>)

Bad prognosis Monocyte consist granular lysozyme Acute Tubular Necrosis (ATN) Mature cell relative Gums bleeding > often Relaps easily

M-6
( ERYTHRO LEUKEMIA )

CONSISTS OF :
ERYTHROBLAST > 50% MYELOBLAST > 30% ,PROMYELOCYTE ,MONOCYTE

PRO NORMOBLAST :
PAS (+) / NORMAL / NEG MEGALOBLASTOID LOBULE NUCLEI, or MULTIPLE

DD : ANEMIA B12 DEFISIENCY

( M6- MYELOBLAST > 30 %)

EASY TO BECOME AML

M-7
( MEGAKARYOCYTIC LEUCEMIA )

Often undiagnose Difficult to be distinguished with :

ALL ( L1-L2 & M1) Pro-megakaryocyte. Cytochemistry platelet peroxidase Immunology monoclonal antibody Electron microscope

If to become myelofibrosis BMP very difficult

THE PRINCIPAL OF THERAPY

Cytostatic drug may impair reproductive capacity of the normal cells Several combined cytostatic drug have been developed Initial therapies are usually affected by leukemic cell lysis which causes: Hyper kalemia Hyper uricemia Nephropathy