LIMFOMA MALIGNUM

HODGKIN

IRZA WAHID
SUBAGIAN HEMATOLOGI & ONKOLOGI MEDIK
FK UNAND / RS DR M DJAMIL PADANG

LIMFOMA MALIGNUM
HODGKIN

DEFINISI
Limfoma malignum Hodgkin adalah
sekelompok keganasan primer limfosit yang
ditandai dengan adanya sel REED STENBERG
SEJARAH
1832 : Thomas Hodgkin
1872 : Langerhans Sternberg Reed
Histopatologis
Analisis PCR : berasal dr folikel sel B yg
mengalami ggn struktur pada imunoglobulin,
mengandung faktor transkripsi sel
apoptosis

Epidemiologi & Faktor Risiko

Prevalence
Incidence

: 1 % of all malignancy
: 7400 new cases / year
(2,8 / 100.000 )
Bimodal age : in the 1st & 5th decades
2-3th & 7th decades
Males more often than females

Beberapa faktor risiko :

Genetik
Immundefisiensi
Agen infeksius : EBV, HIV, HHV 6, CMV
Merokok

Recent Theories of Carcinogenesis

Chemical carcinogenesis

derived from observations by Pott, 1775

major line of mechanistic oncology
Viral theory of carcinogenesis
Two-stage mechanism of Ca.genesis
two processes: initiation, promotion
followed by progression

Mechanisms of
carcinogenesis
Cancer as a multistage process
1. initiation: DNA alteration or cell change
2. tumor-promotion: from single mutated
cell to formation of tumor
3. tumor-progression: development of
malignancy
promotion and progression are normally
held in check by tumor-supressor genes
so, if these genes are affected via
mutation, then cell growth become
uncontrollable

From: Brooks, Chap. 7

Lymphoid generation

Non Burkitts
Lymphocyte
Lymphoplasmocytoid
Plasma cell

STEM CELL
IL-1, IL-2

IL-3

CFU L

IL-2

IL-2
IL-4

CD3+

IL-2
T Lymphoblast

CD

Pro B

IL-4

IL-2

20+CFC BL

CD3-

IL-4

Null cell
IL-2

T Histiocytes

CD

IL-2

30+

IL-12

IL-4

T cell

LAK

B Centroblast

IL-6

B Immunoblast

IL-6

Angio-Immunoblastic

IL-2

B Lymphoblast
IL-4

IL-6

Lymphoid
generation

CFC TL

IL-4

Centrocyte

IL-4
IL-4
Plasmoblast

Th: CD3+CD4+ Lymphoplasmacytoid IL-4

Ts: CD3+CD8+CD16CTL: CD3+CD8+CD16+
Plasma cell

IL-4
IL-6

B cell

NK

CD3-CD56+

PENDEKATAN DIAGNOSTIK
1. Anamnesis
* Pembesaran KGB tidak nyeri
* BB menurun
* Demam
* Keringat malam
* Lemah badan
* Gatal
* Keluhan anemia
* Keluhan organ

2. Pemeriksaan fisik
* Pembesaran KGB

* Kelainan / pembesaran organ

* Tanda obstruksi : VCS, Kompressi medula spinalis

Performance status : WHO, Karnofsky

Lymphadenopathy

Proliferation
and
Transformatio
n

Proliferatio
n

Non
neoplasm /
Infection

Neoplasm

Specific
Benign

Malignant

Secondary
(metastati
c)

Primary

Hodgkin

Non Hodgkin

Non
specific

Apparent Site
High cervical nodes : 29 %
Supraclavicular nodes : 41 %
: 11 %
Mediastinal nodes
: 4%
Axillary nodes
: 13 %
Abdominal nodes
: 1%
Spleen

3. Pemeriksaan Diagnostik

Laboratorium
* Rutin Darah perifer lengkap ( DPL ), Gambaran darah tepi ( GDT )

Anemia, easinofilia, peningkatan LED, limfositosis, limfosit abnormal

* Kimia Klinik Faal hati, Ginjal, As. Urat, LDH

* Imunophenotyping parafin panel CD 20, CD 30, CD 15

Radiologi

* Foto torak CT Scan torak

* USG Abdomen CT Scan abdomen
* Limfografi

Biopsi Gold Standar

BMP & biopsi SST

Khas sel Reed Steinberg

Klasifikasi ( Rye )

1. Tipe lymphocyte predominant

* 10 %
* Limited disease
2. Tipe mixed cellularity
* 60 %
* Mediastinal involvement common, often in young men
3. Tipe lymphocyte depleted
* 20 %
* B symptoms
4. Tipe nodular sclerosis
* 10 %
* Usually advanced

WHO/REAL Classification of Lymphoid

Neoplasms

B-Cell Neoplasms
Mature (peripheral) T neoplasms
Precursor B-cell neoplasm
T-cell chronic lymphocytic leukemia / small
Precursor B-lymphoblastic leukemia/lymphoma
lymphocytic lymphoma
(precursor B-acute lymphoblastic leukemia)
T-cell prolymphocytic leukemia
T-cell granular lymphocytic leukemiaII
Mature (peripheral) B-neoplasms
B-cell chronic lymphocytic leukemia / small lymphocytic
Aggressive NK leukemia
lymphoma
Adult T-cell lymphoma/leukemia (HTLV-1+)
B-cell prolymphocytic leukemia
Extranodal NK/T-cell lymphoma, nasal type#
Lymphoplasmacytic lymphoma
Enteropathy-like T-cell lymphoma**
Splenic marginal zone B-cell lymphoma
Hepatosplenic T-cell lymphoma*
(+ villous lymphocytes)*
Subcutaneous panniculitis-like T-cell lymphoma*
Hairy cell leukemia
Mycosis fungoides/Szary
fungoides/Szary syndrome
Plasma cell myeloma/plasmacytoma
Anaplastic
large cell lymphoma, T/null cell,
Extranodal marginal zone B-cell lymphoma of MALT
type
primary cutaneous type
Nodal marginal zone B-cell lymphoma
Peripheral T-cell lymphoma, not otherwise characterized
(+ monocytoid B cells)*
Angioimmunoblastic T-cell lymphoma
Follicular lymphoma
Anaplastic large cell lymphoma, T/null cell,
Mantle cell lymphoma
primary systemic type
Diffuse large B-cell lymphoma
Hodgkins Lymphoma (Hodgkins Disease)
Mediastinal large B-cell lymphoma
Nodular lymphocyte predominance Hodgkins lymphoma
Primary effusion lymphoma
Classic Hodgkins lymphoma
Burkitts lymphoma/Burkitt cell leukemia
Nodular sclerosis Hodgkins lymphoma (grades 1 and 2)
T and NK-Cell Neoplasms
Lymphocyte-rich classic Hodgkins lymphoma
Precursor T-cell neoplasm
Precursor T-lymphoblastic leukemia/lymphoma
Mixed cellularity Hodgkins lymphoma
(precursor T-acute lymphoblastic leukemia
Lymphocyte depletion Hodgkins lymphoma
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

Not described in REAL classification

Includes the so-called Burkitt-like lymphomas
** Formerly known as intestinal T-cell lymphoma
# Formerly know as angiocentric lymphoma

STADIUM ( Ann Arbor Modifikasi Cotswald 1989 )

* Stadium I Pembesaran 1 KGB regional
I E 1 organ extra limfatik tetapi tidak difus

* Stadium II Pembesaran min.2 KGB regional tapi masih 1 sisi diafragma

II.2 Pembesaran 2 regio KGB,
II E Pembesaran 1 regio KGB + 1 extralimfatik tidak difus
* Stadium III Pembesaran KGB regional / keterlibatan organ extra nodal
2 sisi
diafragma
* Stadium IV Jika mengenai minimal 1 organ extralimfatik, difus dengan
atau
tanpa keterlibatan KGB
A : bila tanpa gejala sistemik,
B : dg gejala sistemik
X : bila ada bulky mass ( > 1/3 torak, > 10 cm untuk KGB

PENATALAKSANAAN
Staging, Faktor risiko
1. Radioterapi
2. Radioterapi + Kemoterapi
3. Kemoterapi

Faktor Risiko
GHSG

- Masa mediastinal besar

- Extra nodal
- LED > 50 (tanpa gejala), > 30 (+ gejala)
- Minimal 3 regio KGB

EORTC / GELA

- Masa mediastinal besar

- Usia > 50
- LED meningkat
- 4 regio atau lebih

Prognostic Factor
EORTC
Very Favorable
All of : Female, Age < 40 yrs, LP, NS,
MMR < 0,35

Favorable
All others

Any of : MMR 0,35, High ESR, 4 sites,

Age

50 yrs

Rekomendasi terapi
Kelompok

Stadium

Rekomendasi

Stadium Dini
(Favorable)

CSI-IIA/B
tanpa fc risiko

EFRT atau
CT (4-6
siklus ) + IFRT
CT (4 6
siklus) + IFRT

Stadium Dini CSI-IIA/B

(Unfavorable) dengan fc
risiko
Stadium
CS IIB + fc
lanjut
risiko, IIIA/B,
IVA/B

CT (6-8
siklus ) + RT

Relaps
Kemoterapi
Radioterapi salvage
Kemoterapi salvage
Transplantasi sum-sum tulang

Kemoterapi
NCI : ABVD & Stanford 5
Regimen

Dosis
(BSA)

Rute

Jadwal

COPP
Cyclophospami
de
Oncovin
Procarbazin
Prednison

28 hari
650
1,4
100
40

IV
IV
PO
PO

1,8
1,8
1-14
1-14

ABVD
Adriamisin
Bleomisin
Vinblastin
Dacarbazin

28 hari
25
10
6
375

IV
IV
IV
IV

1,15
1,15
1,15
1,15

Stanvord V
Mechloretamine
Adriamisin
Vinblastin
Vinkristin
Bleomisin
Etoposide
Prednison
GCSF

Siklus

12 minggu
6
25
6
1,4
5
2 X 60
40

IV
IV
IV
IV
IV
IV
IV
PO
SC

Minggu 1,5,9
Minggu 1,3,5,9,11
Minggu 1,3,5,9,11
Minggu 2,4,6,8,10,12
Minggu 2,4,6,8,10,12
Minggu 3,7,11
Minggu 1 9, tapp 1012

KEMOTERAPI
FASE PERTUMBUHAN SEL
KANKER
M
G2
G1

G0

Sesudah mitosis (M), G1 (altif membentuk

RNA, protein) S ( sintesis DNA) G2 (aktif lagi
membentuk RNA, protein)

Sel aktif berproliferasi G1 pendek

Sel lambat proliferasi G1 panjang

KLASIFIKASI KEMOTERAPI

1. NONSPESIFIK TERHADAP FASE SEL

A. SPESIFIK SIKLUS, NONSPESIFIK FASE
ALKILATING, DEKARBASIN
B. NON SPESIFIK SIKLUS
STEROID, ANTIBIOTIK KECUALI BLEOMISIN
SPESIFIK TERHADAP FASE SEL
A. FASE G 0 SEMUA KEMOTHY AKAN
REFRAKTER
B. FASE G 1 L- ASPARAGINASE
C. FASE S ANTIMETABOLIT, HIDROKSIUREA,
PROKARBAZIN
D. FASE G 2 BLEOMISIN, ALKALOID TANAMAN
E. FASE M ALKALOID TANAMAN

GOLONGAN

SUB
GOLONGAN

ALKILATOR

MUSTAR NITROGEN
DERIVAT ETILENAMIN
ALKIL SULFONAT
NITROSURIA

SIKLOFOSPAMID, MELFALAN, KLORAMBUSIL

TIOTEPA
BUSULFAN
KARMUSTIN, LOMUSTIN, SAMUSTIN

ANTI
METABOLIT

ANALOG PIRIMIDIN
ANALOG PURIN
ANTAGONIS FOLAT

5-FU, SITARABIN, 6 AZAURIDIN, FLOKSURIDIN

6-MERKAPTOPURUN, 6-TIOGUANID
METOTREKSAT

ALKALOID VINKA
ANTIBIOTIK
ENZIM

VINBLASTIN, VINKRISTIN
DAKTINOMISIN, MITOMISIN,
ANTRASIKLIN : DAUNORUBISIN & DOXORUBISIN
L-ASPARAGINASE

ADRENOKORTIKOID
PROGESTIN
ESTROGEN
ANDROGEN

PREDNISON
HIDROKSIPROGESTERON, MEGESTROL
DIETILSTILBESTEROL, ETINILESTRADIOL
TESTOTERON, FLUOKSIMESTERON

FOSFOR
YODIUM

NATRIUM FOSFAT
NATRIUM YODIDA

SUBSTITUSI UREA

HIDROKSIUREA
PROKARBAZIN

PRODUK
ALAMIAH

HORMON

ISOTOP
RADIOAKTIF
LAIN-LAIN

DERIVAT METIHIDRAZIN

OBAT

PERHATIAN
TOKSISITAS OBAT
SST, SALURAN CERNA, SEL FOLIKEL RAMBUT

KONTRA INDIKASI
* KU BURUK SKALA KARNOFSKY KURANG 30
* DEPRESI SST
* KEMOTERAPI SEBELUMNYA KURANG 3 MINGGU
* INFEKSI AKUT
* KEHAMILAN TRIMESTER 1
* PEMBEDAHAN BESAR ( 10 20 HARI )
* GGN PSIKIATRIK BERAT
* TAK MUNGKIN EVALUASI YANG BAIK / LENGKAP

RISIKO LAIN

* EFEK IRITASI KULIT

* EFEK KARSINOGENIK
* EFEK MUTAGENIK

KARNOFSKY SCALE
100 %
90 %
80 %
70 %
60 %
50 %
40 %
30 %
20 %
10 %
0%

: AKTIFITAS NORMAL, KELUHAN (-), GEJALA PENYAKIT (-)

: AKTIFITAS NORMAL, KELUHAN (+), GEJALA PENYAKIT (+)
: AKTIFITAS NORMAL DENGAN USAHA, BEBERAPA GEJALA
: AKTIFITAS NORMAL (-), DAPAT MENGURUS DIRI SENDIRI
: AKTIFITAS NORMAL (-), KADANG PERLU BANTUAN
: BANYAK PERLU BNATUAN
: PERLU PERAWATAN DAN BANTUAN KHUSUS
: TIDAK MAMPU BANGUN, HARUS RAWAT RS
: SAKIT BERAT
: MENDEKATI AJAL
: MENINGGAL

ECOG SCALE
0
1
2
3
4
5

: NORMAL
: GEJALA ADA, TERTOLERANSI
: TAK BISA AKTIFITAS NORMAL, KURANG 50 % BEDREST
: SAKIT BERAT, LEBIH 50 %,BEDREST, MASIH MAMPU BERDIRI
: SAKIT AMAT BERAT, 100 % DITEMPAT TIDUR
: MENINGGAL

PERSIAPAN KEMOTERAPI
1.
2.
3.

4.
5.
6.
7.
8.
9.

INFORM CONSENT
INFORMASI MANFAAT DAN EFEK SAMPING
PEMERIKSAAN DARAH
* HB, > 10 GR%, LEU > 5000 /MM3, TROMB > 100.000/MM3
* SGOT, SGPT, UREUM, KREATININ, ASAM URAT
K/P EKG / EKOKARDIOGRAFI
DIET MB TKTP
INFUS NACL 0,9%, DEXTROSE 5 %
ANTIMUNTAH, METOKLORPAMID / ONDASETRON
LIHAT PROTAP PENYAKIT
MONITORING EFEK SAMPING