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