Leukemia, Epidemiologi, Patogenesis, Leukemia Akut

LEUKEMIA :

KEGANASAN SEL DARAH PUTIH / JARINGAN. DITANDAI ADANYA :

PROLIFERASI DAN AKUMULASI TAK TERKONTROL DARI INDUK SEL DARAH PUTIH DAN TURUNANNYA , DAPAT MELIBATKAN BEBERAPA JALUR SEL LAIN DARI SEL STEM SUMSUM TULANG.

- PERTUMBUHAN SEL TAK TERKONTROL
- DAPAT MENGINFILTRASI KEJARINGAN TUBUH LAIN

DISCOVERED BY DR. ALFRED VELPEAU IN FRANCE, 1827
NAMED BY PATHOLOGIST RUDOLF VIRCHOW IN GERMANY, 1845

OVERVIEW

KONSEP BIOLOGI
EPIDEMIOLOGI/ INSIDENSI
PATOGENESIS
DIAGNOSIS :

- GEJALA DAN TANDA KLINIS
- LABORATORIUM : HEMATOLOGI , SITOKIMIA, SITOGENETIKA.
- BMP (BONE MARROW PUNCTION/ BMA), BMB (BONE
MARROW BIOPTIE ) : SITOMORFOLOGI, IMMUNOPHENOTYPING.

PENATALAKSANAAN
PROGNOSIS

INSIDENSI :

LEULKEMIA AKUT DPT TERJADI PD SEMUA UMUR :

- ACUTE LYMPHOBLASTIC LEUKEMIA (ALL) -> ANAK
- ACUTE MYELOBLASTIC LEUKEMIA (AML) -> DEWASA

LEUKEMIA KRONIS BIASANYA PADA DEWASA :

- CLL (CHRONIC LYMPHOCYTIC LEUKEMIA) JARANG
PADA ANAK, PADA ORANG DEWASA < 40 TAHUN
- CML (CHRONIC MYELOBLASTIC LEUKEMIA) PADA
DEWASA, PUNCAK PD UMUR 30-50 TAHUN.

Menurut perjalanan penyakit :

Leukemia dikelompokan 2 grup utama :
Akut :

Munculnya mendadak
Perjalanannya sangat agresif.
Terdiri sel berdeferensiasi
Jelek dengan timbunan sel blast (sel muda ).

Kronis :

Munculnya perlahan
Kurang agresif
Didominasi sel dewasa, terdapat beberapa sel muda (limfoblast /mieloblast).

PATOGENESIS :

Perubahan molekul DNA sel hemopoetik
Perubahan gen normal tertentu
Transformasi maligna
Proliferasi klonal abnormal sel induk/ sel progenitor

LEUKEMIA AKUT

OBJECTIVE :

Define acute leukemia
Classify leukemia
Understand the pathogenesis
Understand the pathophysiology
Able to list down the laboratory investigations required for diagnosis
Understand the basic management of leukemia patients

ACUTE LEUKAEMIA

Define : heterogenous group of malignant disorders which is characterised by uncontrolled clonal and accumulation of blasts cells in the bone marrow and body tissues
Sudden onset
If left untreated is fatal within a few weeks or months

SIGNIFICANCE OF ADULT ACUTE LEUKEMIA :

A hematologic urgency
Usually fatal within weeks to months without chemotherapy
With treatment, high mortality due to disease or treatment-related complications (unlike childhood acute leukemia)
Notify Hematologist promptly if acute leukemia is suspected

Causes of acute leukemias :

Idiopathic (most)
Underlying Hematologic Disorders
Chemicals, Drugs
Ionizing Radiation
Viruses (htlv I)
High Level Radiation/toxin Exposure
Hereditary/genetic Conditions

Develop as a result of a genetic alteration within single cell in the bone marrow
a). Epidemiological evidence :
       1. Hereditary Factors
            - Fanconi’s anaemia
            - Down’s syndrome
            - Ataxia telangiectasia
       2. Radiation, Chemicals and Drugs
       3. Virus related Leukemias             - Retrovirus :- HTLV 1 & EBV
b). Molecular Evidence
      * Oncogenes :
          - Gene that code for proteins involved in cell proliferation or differentiation
      * Tumour Suppressor Genes :
          - Changes within oncogene or suppressor genes are necessary to cause transformation.
          - Oncogene can be activated by :
            · chromosomal translocation
            · point mutations
            · inactivation
     * In general, several genes have to be altered to effect neoplastic transformation.

Patogenesis

Perubahan molekul DNA sel hemopoetik
Perubahan gen normal tertentu
Transformasi maligna
Proliferasi klonal abnormal sel induk/progenitor

METABOLIC IMBALANCE :

Due to disease or treatment
Hyponatremia vasopressin-like subst. by myeloblast
Hypokalemia due to lysozyme release by myeloblast
Hyperuricaemia- spont lysis of leukemic blast release purines into plasma.

PATHOPHYSIOLOGY

Acute leukemia cause morbidity and mortality through :
A. Deficiency in blood cell number and function
B. Invasion of vital organs
C. Systemic disturbances by metabolic imbalance

A. Deficiency in blood cell number or function
   * Infection
      - Most common cause of death
      - Due to impairment of phagocytic function
        and neutropenia.
   * Hemorrhage
      - Due to thrombocytopenia or DIC or liver disease.
   * Anaemia
      - normochromic-normocytic
      - severity of anaemia reflects severity of disease
      - Due to ineffective erythropoiesis

B. Invasion of vital organs
     - vary according to subtype
* Hyperleukocytosis
     - cause increase in blood viscosity
     - Predispose to microthrombi or acute    bleeding
     - Organ invole : brain, lung, eyes

Baca Juga

     - Injudicious used of packed cell transfusion precipitate hyperviscosity.
* Leucostatic tumour
     - Rare
     - Blast cell lodge in vascular system forming
       macroscopic pseudotumour – erode vessel wall cause
       bleeding
* Hidden site relapse
    - testes and meninges

C. Systemic disturbances by metabolic imbalance

Attacks the immune system
Infections
Anemia
Weakness
No more regular white blood cells, red blood cells, and platelets
Blasts clog blood stream and bone marrow
Paraneoplstic syndrome

LLA : Klasifikasi Imunologik

Null ALL
Common ALL
T ALL
B ALL

DIAGNOSIS :

GEJALA DAN TANDA KLINIS
LABORATORIUM
BMP (BONE MARROW PUNCTION/ BONE
MARROW ASPIRATION )
BMB (BONE MARROW BIOPTIE ).

GEJALA KLINIS:
- LEMAH BADAN, MUDAH CAPAI, - PANAS, - PEDARAHAN
- ORGANOMEGALI
- LIMPADENOPATIA
- STERNAL TENDERNESS
- HIPERTROFI GINGGIVA, KULIT, JAR.LUNAK/ MENINGEN -> AML M4/ M5.
- DIC/ TENDENSI PERDARAHAN APL, ACA.
- AKIBAT LEUKOSTASIS ( SESAK NAFAS, NYERI DADA, NYERI KEPALA, GANGGUAN MENTAL, PARESIS NN.CRAN., PRIAPISM)