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 Leukemia limfoblastik akut
( Tu. Dewasa muda ) ( Tu. Anak-anak )

Leukemia mielositik kronik Leukemia limfositik kronik

( Dewasa muda + orang tua ) ( 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 4%  4% Leukemia
lymphoma
 3% Non-Hodgkin
Esophagus 4% lymphoma
Liver & intrahepatic 3%  3% Uterine corpus
bile duct
 2% Multiple myeloma
Urinary bladder 3%
 2% Brain/ONS
Kidney 3%
24% All other sites
All other sites 21%
Men Women
290,890 272,810

ONS=Other nervous system.

Source: American Cancer Society, 2004.
DISTRIBUSI LEUKEMIA DI RSKD
(1993-2000)

Agus Kosasih et al.

 Diagnosis

Klinis
Sitomorfologi

Sitokimia

Immunophenotype

Sitogenetik

Molecular
LEUKEMIA MIELOSITIK KRONIK
 Myeloproliferative disorders
 Typical CML
 variant : chronic eosinophilic leukemia
chronic basophilic leukemia
chronic neutrophilic leukemia
 Idiophatic Myelofibrosis
 Polycythemia vera
 Essential thrombocytemia
 Chronic myelomonocytic leukemia
 Atypical CML
Figure
10 3. Classification of myeloproliferative neoplasms on the basic of
molecular pathogenetic characteristics. (Campbell PJ et al, 2006)
 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 83
Weight loss 61
Abdominal fullness & anorexia 38
Easy bruising or bleeding 35
abdominal pain 33
fever 11
splenomegali 95
sternal tenderness 78
lymphadenophaty 64
hepatomegaly 48
purpura 27
retinal hemmorhage 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
 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 ( WHO, 2001 )

A. 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
T and NK-Cell Neoplasms 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 leukemia II
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/S ézary syndrome
Anaplastic large cell lymphoma, T/null cell,
primary cutaneous type
Peripheral T-cell lymphoma, not otherwise characterized
Angioimmunoblastic T-cell lymphoma
Anaplastic large cell lymphoma, T/null cell,
primary systemic type
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