LEUKEMIALEUKEMIA

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

ETIOLOGYETIOLOGY

The factors that involve:

A. Chromosome disorders gene of cell proliferation regulator damage suppressor gene

B. Oncogene Oncogene activation neoplastic transformation

Certain cause hasn’t known yet

D. Environment factor

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

C. Host factor

Chromosome susceptibility genetic damage

malignant transformation

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

4. Chronic bone marrow dysfunction

CLASSIFICATIONCLASSIFICATION

I. FAB classification (French-American British) morphology

- Treatment approach

- Disease development

- Prognosis determining

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

A. ACUTE

LEUKEMIA :

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 leukemia2. Subleukemic leukemia

B. Cell surface markers immunologic

C. Cytochemist PAS, Peroxides, Sudan Black:

- Lymphoblast

- Myeloblast

- Monoblast

E. Enzyme

D. Chromosome Analysis Philadelphia CML

INCIDENSINCIDENS

- 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 ANLLChild 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 CLINICAL MANIFESTATIONS

1. Suppress in bone marrow bone marrow failure pancytopenia

2. Extra medullar infiltration

1. Anemia:- common symptom of anemia

- acute onset & progressive

2. Granulocytopenia:- fever- easy to get infection

3. Thrombocytopenia bleeding- spontaneous/ mild trauma - skin, mucous

BONE MARROW FAILURE

EXTRA MEDULLAR INFILTRATION

1. Lymphadenopathy

2. Splenomegaly

3. Hepatomegaly

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

4. Symptom of CNS infiltration

5. Gonad- Testes: source of extramedularry relapse

6. Ren

7. Gastrointestinal tract- gut infiltration - ulceration, invagination

8. Eye

BLOOD PROFILEBLOOD 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

Leukocyte reaction:

hyperleukocytosis with immature cell

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

- lymphoid: pertusis, mononucleosis infectiosa,

TBC

Leukemoid Reaction:

TREATMENTTREATMENT

Goal/treatment principal:

1. Remission & maintenance recovery

2. To overcome symptoms/consequence

disease & drug

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

For the first aim chemotherapy

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%

REMISSION:

- Antimicrobial infection

- blood component anemia, thrombocytopenia,

granulocytopenia

- Hematopoietic Growth Factor:G-CSFGM-CSF

- Improve general condition

TO OVERCOME SYMPTOMS/CONSEQUENCE Supportive:

PROGNOSISPROGNOSIS

- Without treatment:

> 50% death < 6 month

- With adequate treatment: > 60% remission cALL

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

Risk Factor for ALL:

- infection the main cause of death

- Bleeding: Gastrointestinal & Intracranial

Cause of death: