Transcript Slide 1

DIAGNOSIS & PENATALAKSANAAN
LEUKEMIA KRONIK
IRZA WAHID
SUBBAGIAN HEMATOLOGI DAN ONKOLOGI MEDIK
BAGIAN I. PENY DALAM
FK UNAND - RS DR M DJAMIL PADANG
LEUKEMIA
Definisi : Abnormalitas Proliferasi / diferensiasi sel induk darah
Serial Mieloid
Serial Limfoid
Leukemia mieloblastik akut
( Tu. Dewasa muda )
Leukemia limfoblastik akut
( Tu. Anak-anak )
Leukemia mielositik kronik
( Dewasa muda + orang tua )
Leukemia limfositik kronik
( Semua umur )
Hematopoeitik :
Sum-sum tulang --------------------------------> Darah tepi
I. Myeloid progenitor cell
A.Erythro-MK progenitor cell
Eritropoesis  eritrosit  Anemia / Polisitemia
Megakariopoesis  trombosit  Trombositosis / Trombositopenia
B.Gran-mono progenitor cell
Granulopoesis  leukosit  Leukopenia / Leukositosis
Monositopoesis  monosit  Monositopenia / Monositosis
II. Lymphoid progenitor cell
Limfopoesis limfosit  Limfositopenia / Limfositosis
 sel plasma
Extramedular ------------------------------------> Hati / Limpa
INSIDEN : SEKITAR 3 %
2004 Estimated US Cancer Deaths
Lung & bronchus
32%
25% Lung & bronchus
Prostate
10%
15%
Breast
Colon & rectum
10%
10%
Colon & rectum
Pancreas
5%

6% Ovary
Leukemia
5%

6% Pancreas
Non-Hodgkin
lymphoma
4%

4% Leukemia
Esophagus
4%

3% Non-Hodgkin
lymphoma
Liver & intrahepatic
bile duct
3%

3% Uterine corpus
Urinary bladder
3%

2% Multiple myeloma
Kidney
3%

2% Brain/ONS
All other sites
24%
21%
Men
Women
290,890 272,810
ONS=Other nervous system.
Source: American Cancer Society, 2004.
All other sites
DISTRIBUSI LEUKEMIA DI RSKD
(1993-2000)
20%
28%
5%
47%
CML
CLL
AML
ALL
Agus Kosasih et al.
Diagnosis
Klinis
Sitomorfologi
Sitokimia
Immunophenotype
Sitogenetik
Molecular
LEUKEMIA MIELOSITIK KRONIK
Myeloproliferative disorders
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Typical CML
 variant : chronic eosinophilic leukemia
chronic basophilic leukemia
chronic neutrophilic leukemia
Idiophatic Myelofibrosis
Polycythemia vera
Essential thrombocytemia
Chronic myelomonocytic leukemia
Atypical CML
Figure 3. Classification of myeloproliferative neoplasms on the basic of
molecular pathogenetic characteristics. (Campbell PJ et al, 2006)
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DEFINITION
CLONAL STEM CELL DISORDERS
 INCREASED PROLIFERATION OF
MYELOID ELEMENTS AT ALL STAGES
DIFFERENTIATION

Translokasi kromosom 9 dan 22 :
Philadelphia chromosome (CML)
Fusi gen BCR - ABL
Leukemogenesis
Perjalanan Penyakit
1. Fase
kronik
CLINICAL & SYMPTOMS
%
Fatigue
Weight loss
Abdominal fullness & anorexia
Easy bruising or bleeding
abdominal pain
fever
splenomegali
sternal tenderness
lymphadenophaty
hepatomegaly
purpura
retinal hemmorhage
83
61
38
35
33
11
95
78
64
48
27
21
PERIPHERAL BLOOD & BONE MARROW
anemia ringan, normositik normokrom
leukositosis 20 – 60.000 /mm3
trombosit 500 – 600000 /mm3
morfologi darah tepi : tu mielosit & netrofil segmen
 SST : hiperseluler, myeloblast  netrofil segmen
2. Accelerated phase
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



Panas /B.B turun tanpa sebab
Splenomegali yg sulit dikendalikan
Progressieve pancytopenie
Progressieve leukocytosis yg cepat
Kenaikan blast (>10%) in blood or bone
marrow
Lebih dari 20% blast + promyelocyte in blood
or bone marrow
Basofilia (>20%)
Additionale chromosomale abnomalities
(e.g. iso 17, +8, 2e t (9;22))
Resintent with standard cytostatica
3. Blastic crisis phase
>20% blast di darah perifer atau >30%
sumsum tulang atau
 >30% blast + promyelocyte di darah
perifer atau
 >50% blast + promyelocyte di sumsum
tulang atau di extramedullaire lokalisatie

Penatalaksanaan
1. Supportif
2. Kemoterapi
Hydroxi urea ( Hydrea 500 mg)
 Fase kronik / akselerasi
* Leukosit 20000 – 150000  50 mg/kgbb/hr 3 dosis s/d leukosit < 20.000
* Leukosit > 150.000  leukoferesis  20 mg/kgb s/d leu 5000 – 15000
 Fase Krisis blast
 Hidroxyurea 20 mg/kgbb+ 6 MP1,5–2,5 mg/kgbb + Pred 60 /m2
 Median survival : 4 – 5 yrs

Alternatif
 Busulfan  Median survival : 4 – 5 yrs
 Interferon alfa  Median survival : 5 – 8 yrs
 Imatinib mesylate
 Dasatinib

Definitif
 Transplantasi sum-sum tulang
 Median survival : 7 – 10 yrs
Leukemia Limfositik Kronik
Lymphoma Classification
A.
( WHO, 2001 )
B-Cell Neoplasms
I. Precursor B-cell neoplasm : Precursor B- acute lymphoblastic
leukemia / lymphoblastic lymphoma (B-ALL, LBL)
II. Mature (peripheral) B-neoplasms
a.
B-cell chronic lymphocytic leukemia
b.
B-cell prolymphocytic leukemia
c.
Lymphoplasmacytic lymphoma
d.
Mantle cell lymphoma
e.
Folliculer lymphoma
f.
Splenic marginal zone B-cell lymphoma
g.
Hairy cell leukemia
h.
Plasma cell myeloma/plasmacytoma
i.
Extranodal marginal zone B-cell lymphoma of MALT type
j
Nodal marginal zone B-cell lymphoma (+ monocytoid B cells)
k.
Diffuse large B-cell lymphoma
l.
Burkitt’s lymphoma/Burkitt cell leukemia
LYMPHOMA GRADATION ( NCCN 2010 )
Indolent (slow growing) B-cell lymphomas
•Follicular lymphoma
•Chronic lymphocytic leukemia
•MALT
•Splenic marginal zone lymphoma
•Nodal marginal zone
Aggressive (fast growing) B-cell lymphomas
• Diffuse large B-cell lymphoma
•Mantle cell lymphoma
Highly aggressive B-cell lymphomas
•Burkitt lymphoma
•Lymphoblastic lymphoma / AIDS-related B-cell
WHO/REAL Classification of Lymphoid
Neoplasms
T and NK-Cell Neoplasms
Precursor T-cell neoplasm
Precursor T-lymphoblastic leukemia/lymphoma
(precursor T-acute lymphoblastic leukemia
Formerly known as lymphoplasmacytoid lymphoma or immunocytoma
II Entities formally grouped under the heading large granular lymphocyte
leukemia of T- and NK-cell types
* Provisional entities in the REAL classification
‡
Mature (peripheral) T neoplasms
T-cell chronic lymphocytic leukemia
T-cell prolymphocytic leukemia
T-cell granular lymphocytic leukemiaII
Aggressive NK leukemia
Adult T-cell lymphoma/leukemia (HTLV-1+)
Extranodal NK/T-cell lymphoma, nasal type#
Enteropathy-like T-cell lymphoma**
Hepatosplenic γδ T-cell lymphoma*
Subcutaneous panniculitis-like T-cell lymphoma*
Mycosis fungoides/Sézary syndrome
Anaplastic large cell lymphoma, T/null cell,
primary cutaneous type
Peripheral T-cell lymphoma, not otherwise characterized
Angioimmunoblastic T-cell lymphoma
Diagnosis
* Gejala klinis + pemeriksaan fisik
* Laboratorium :Leukositosis, limfositosis > 15000 /mm3
anemia normositer/krom, trombositopenia
* Sitogenetik kelainan Khr. 12,13,14 kdg khr 6, 11
Stadium
0
: Limfositosis > 15000, SST limfositosis > 30 %
1
: Stad.0 + pembesaran KGB
2
: Stad. 0 + hepatosplenomegali dengan / tanpa
pemebesaran KGB
3
: Stad. 0 + anemia (Hb < 11 gr% ) dgn / tanpa stad
1, 2
4
: Stad.0 + trombositopenia ( < 100000 / mm3 )
Penatalaksanaan
1. Terapi umum
2. Terapi khusus diberikan bila :
- anemia, trombositopenia, limfositosis progresif, sepsis rekuren,
anemia hemolitik autoimun, splenomegali masif, KGB sangat besar
- Klorambusil 0,1 – 0,2 mg / kgBB ( Leukeran 5mg ),
leukosit. turun 50 % dosis 50 %, bila leukosit < 15000 obat distop
- Prednison atas indikasi : a. infiltrasi SST dengan pansitopeni
b. Hemolisis atau trombositopeni otoimun
 klorambusi 0,7 mg / KgBB tiap minggu
prednison 0,5 mg / kgBB / hari selama 7 hari tiap bulan, bila
sudah terkontrol 6 – 8 bulan obat distop.
- Siklofospamid 200 mg / m2 tiap hari selama 5 hari tiap 3 minggu atas indikasi
Bila korambusil tak tertoleransi / tak ada kemajuan
- Fludarabin 25 mg / m2 tiap hari selama 5 hari tiap 3 minggu selama 6 – 8 bulan
atas indikasi ciklofospamid gagal.
- Radioterapi apabila Splenomegali masif , Penekanan bronkus / vena kava
- Gama globulin 200 – 400 mg / kgBB tiap 3 minggu bila terjadi rekuren infeksi /
hipogamaglobulin