LEUKEMIA

Malignancy of hemopoietic system: Malignant transformation a progenitor/precursor of blood cell clone of malignant cell pathologic proliferation (abnormal) & uncontrolled will cause :

- Suppress in marrow bone marrow failure - Infiltration to the other tissues

ETIOLOGY
Certain cause hasnt known yet
The factors that involve:
A. Chromosome disorders

gene of cell proliferation regulator damage suppressor gene

B. Oncogene Oncogene activation neoplastic transformation

C. Host factor
Chromosome susceptibility genetic damage malignant transformation

1. Familial
2. Congenital chromosome disorders 3. Congenital immune deficiency

4. Chronic bone marrow dysfunction

D. Environment factor
1. Radiation 2. Chemical & drugs 3. Virus: HTLV-1 & Epstein Barr

CLASSIFICATION
I. FAB classification (French-American British) morphology - Treatment approach - Disease development - Prognosis determining

A. ACUTE LEUKEMIA :
1. Acute Lymphoblastic Leukemia (ALL) L1: small cell, a little cytoplasma, homogen often in child L2: large cell, the cytoplasma is more wide,

heterogen adult
L3: larger cell, the cytoplasma:

wide-basophilic,
homogen, vacuolization Burkitt

2. Acute Non-Lymphoblastic Leukemia(ANLL)

M1 (AML): myeloblast without maturation

M2 (AML): myeloblast with maturation

M3 (APL): hypergranular promyelocyte

M4 (Acute Myelomonocytic Leukemia):

granulocyte & monocyte maturation promonocyte & monocyte: >20%

M5 : Acute Monocytic Leukemia M6 : Eritroleukemia M7: Acute Megakarioblastic leukemia

B. CHRONIC LEUKEMIA
1. Chronic myelocytic leukemia (CML) 2. Chronic lymphocytic leukemia

II. Other classification

A. The number of leukocyte: 1. Leukemic leukemia 2. Subleukemic leukemia B. Cell surface markers immunologic

C. Cytochemist PAS, Peroxides, Sudan Black: - Lymphoblast - Myeloblast

- Monoblast
E. Enzyme

D. Chromosome Analysis
Philadelphia CML

INCIDENS
- 1/100.000 of population - The frequency of each type: - ALL : > 80% - ANLL : 10% - CML : 2%

- CLL

: not found in children.

ACUTE LEUKEMIA
Found n all age: Adult mieloblastic ANLL Child limfoblastic ALL 2 - 5 years

Immunologic marker (surface markers) ALL:

1. Non-T Non-B ALL : - Common ALL (cALL antigen) mostly in children the best prognosis - Null ALL 2. Pre-B ALL 3. B-ALL

4. T-ALL

CLINICAL MANIFESTATIONS
1. Suppress in bone marrow bone marrow failure pancytopenia
2. Extra medullar infiltration

BONE MARROW FAILURE

1. Anemia: - common symptom of anemia - acute onset & progressive 2. Granulocytopenia: - fever - easy to get infection 3. Thrombocytopenia bleeding - spontaneous/ mild trauma - skin, mucous

EXTRA MEDULLAR INFILTRATION

1. Lymphadenopathy 2. Splenomegaly 3. Hepatomegaly

4. Symptom of CNS infiltration When diagnosed: 70% CNS infiltration without any sign - Often in T cell ALL - Meningeal syndrome: intra cranial pressure symptom of meningeal signs

- LCS: pleocytosis blast cell

- Source of extramedularry relapse

5. Gonad - Testes: source of extramedularry relapse

6. Ren
7. Gastrointestinal tract - gut infiltration - ulceration, invagination 8. Eye

BLOOD PROFILE
1. Peripheral Blood: - Anemia normocytic normochrom - Thrombocytopenia

- Leukocyte: (>60%),
(20%) and normally ( 15%) - Blast cell leucocytosis Mieloblast: Auer rod

2. BONE MARROW: -Hypercellular dominated by blast cell (leukemia cell) - Suppress of normal hemopoesis decreasing of normal elemen

Examination of bone marrow is important to

distinguish leukemia with: - Aplastic Anemia - ITP - Leukemoid Reaction

Leukemoid Reaction:
Leukocyte reaction: hyperleukocytosis with immature cell

- myeloid: infection, pyogen, massive bleeding, TBC, hemolysis. TBC

- lymphoid: pertusis, mononucleosis infectiosa,

TREATMENT

Goal/treatment principal: 1. Remission & maintenance recovery 2. To overcome symptoms/consequence

disease & drug

For the first aim chemotherapy STRATEGY:

1. Induction - remission
2. CNS Prophylactic 3. Maintainance of remission: a. consolidation/ intensification b. maintenance & reinduction

4. Bone marrow transplantation

5. Cessation of therapy

REMISSION:
1. Complete remission:

- The symptoms disappear

- All element of blood smear: normal & no blast - Blast in bone marrow < 5% 2. Incomplete remission:

- Clinically look healthy - 2 of 3 element of blood smear normal - Blast in bone marrow 6 - 10%

TO OVERCOME SYMPTOMS/CONSEQUENCE Supportive:

- Antimicrobial infection
- blood component anemia, thrombocytopenia, granulocytopenia - Hematopoietic Growth Factor: G-CSF GM-CSF - Improve general condition

PROGNOSIS
- Without treatment: > 50% death < 6 month - With adequate treatment: > 60% remission cALL

Risk Factor for ALL:

1. Age: < 1 year and > 10 year 2. Leukocyte: > 50.000/mm3 3. Sex: boy 4. Mediastinal mass 5. CNS leukemia 6. Type of leukemia: ALL cell T, cell B & Pre-B

7. Philadelphia chromosome

Cause of death:
- infection the main cause of death - Bleeding:

Gastrointestinal & Intracranial