LIMFOMA MALIGNUM HODGKIN

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

LIMFOMA MALIGNUM HODGKINDEFINISILimfoma malignum Hodgkin adalah sekelompok keganasan primer limfosit yang ditandai dengan adanya sel REED STENBERGSEJARAH1832 : Thomas Hodgkin1872 : Langerhans Sternberg Reed Histopatologis Analisis PCR : berasal dr folikel sel B yg mengalami ggn struktur pada imunoglobulin, mengandung faktor transkripsi sel apoptosis

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

Beberapa faktor risiko :Genetik ImmundefisiensiAgen infeksius : EBV, HIV, HHV 6, CMVMerokok

Recent Theories of CarcinogenesisChemical carcinogenesisderived from observations by Pott, 1775major line of mechanistic oncology Viral theory of carcinogenesisTwo-stage mechanism of Ca.genesistwo processes: initiation, promotionfollowed by progression

Mechanisms of carcinogenesisCancer as a multistage process1. initiation: DNA alteration or cell change2. tumor-promotion: from single mutated cell to formation of tumor3. tumor-progression: development of malignancypromotion and progression are normally held in check by tumor-supressor genes so, if these genes are affected via mutation, then cell growth become uncontrollableFrom: Brooks, Chap. 7

Lymphoid generationLymphocyteLymphoplasmocytoidPlasma cell

Lymphoid generationB Lymphoblast Angio-ImmunoblasticB ImmunoblastB CentroblastCentrocytePlasma cellLymphoplasmacytoidT cell B cellCFU LCFC TLCFC BLIL-12IL-2Pro BLAKNKIL-2IL-4IL-2IL-6IL-6IL-2IL-4IL-4T LymphoblastIL-4IL-4IL-4IL-2IL-4IL-6IL-4IL-2IL-6STEM CELLIL-4IL-1, IL-2IL-3PlasmoblastIL-4CD3+Null cellIL-2CD3-CTL: CD3+CD8+CD16+CD3-CD56+Ts: CD3+CD8+CD16-Th: CD3+CD4+CD20+T HistiocytesCD30+

PENDEKATAN DIAGNOSTIK1. 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

Primary

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

3. Pemeriksaan DiagnostikLaboratorium* 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 NeoplasmsB-Cell NeoplasmsPrecursor B-cell neoplasmPrecursor B-lymphoblastic leukemia/lymphoma (precursor B-acute lymphoblastic leukemia)Mature (peripheral) B-neoplasmsB-cell chronic lymphocytic leukemia / small lymphocytic lymphomaB-cell prolymphocytic leukemiaLymphoplasmacytic lymphomaSplenic marginal zone B-cell lymphoma (+ villous lymphocytes)*Hairy cell leukemiaPlasma cell myeloma/plasmacytomaExtranodal marginal zone B-cell lymphoma of MALT typeNodal marginal zone B-cell lymphoma (+ monocytoid B cells)*Follicular lymphomaMantle cell lymphomaDiffuse large B-cell lymphomaMediastinal large B-cell lymphomaPrimary effusion lymphomaBurkitts lymphoma/Burkitt cell leukemiaT and NK-Cell NeoplasmsPrecursor T-cell neoplasmPrecursor 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 neoplasmsT-cell chronic lymphocytic leukemia / small lymphocytic lymphomaT-cell prolymphocytic leukemiaT-cell granular lymphocytic leukemiaII Aggressive NK leukemiaAdult T-cell lymphoma/leukemia (HTLV-1+)Extranodal NK/T-cell lymphoma, nasal type#Enteropathy-like T-cell lymphoma**Hepatosplenic T-cell lymphoma*Subcutaneous panniculitis-like T-cell lymphoma*Mycosis fungoides/Szary syndromeAnaplastic large cell lymphoma, T/null cell, primary cutaneous typePeripheral T-cell lymphoma, not otherwise characterized Angioimmunoblastic T-cell lymphomaAnaplastic large cell lymphoma, T/null cell, primary systemic typeHodgkins Lymphoma (Hodgkins Disease)Nodular lymphocyte predominance Hodgkins lymphomaClassic Hodgkins lymphomaNodular sclerosis Hodgkins lymphoma (grades 1 and 2)Lymphocyte-rich classic Hodgkins lymphomaMixed cellularity Hodgkins lymphomaLymphocyte depletion Hodgkins lymphoma

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 sistemikX : bila ada bulky mass ( > 1/3 torak, > 10 cm untuk KGB

PENATALAKSANAAN

Staging, Faktor risiko

1. Radioterapi

2. Radioterapi + Kemoterapi

3. Kemoterapi

Faktor RisikoGHSG- 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 FactorEORTCVery FavorableAll of : Female, Age < 40 yrs, LP, NS, MMR < 0,35

FavorableAll others

Any of : MMR 0,35, High ESR, 4 sites, Age 50 yrs

Rekomendasi terapi

KelompokStadiumRekomendasiStadium Dini(Favorable)CSI-IIA/B tanpa fc risikoEFRT atau CT (4-6 siklus ) + IFRTStadium Dini(Unfavorable)CSI-IIA/B dengan fc risikoCT (4 6 siklus) + IFRTStadium lanjutCS IIB + fc risiko, IIIA/B, IVA/BCT (6-8 siklus ) + RT

RelapsKemoterapiRadioterapi salvageKemoterapi salvageTransplantasi sum-sum tulang

Kemoterapi NCI : ABVD & Stanford 5

RegimenDosis (BSA)RuteJadwalSiklusCOPP

CyclophospamideOncovinProcarbazinPrednison

6501,410040

IVIVPOPO

1,81,81-141-1428 hariABVD

AdriamisinBleomisinVinblastinDacarbazin

25106375

IVIVIVIV

1,151,151,151,1528 hariStanvord V

MechloretamineAdriamisinVinblastinVinkristinBleomisinEtoposidePrednisonGCSF

62561,452 X 6040

IVIVIVIV IVIV IVPO SC

Minggu 1,5,9Minggu 1,3,5,9,11Minggu 1,3,5,9,11Minggu 2,4,6,8,10,12Minggu 2,4,6,8,10,12Minggu 3,7,11Minggu 1 9, tapp 10-1212 minggu

KEMOTERAPI KANKERFASE PERTUMBUHAN SEL

M

G2G1G0

SSesudah mitosis (M), G1 (altif membentuk RNA, protein) S ( sintesis DNA) G2 (aktif lagi membentuk RNA, protein)

Sel aktif berproliferasi G1 pendekSel lambat proliferasi G1 panjang

KLASIFIKASI KEMOTERAPINONSPESIFIK TERHADAP FASE SELA. SPESIFIK SIKLUS, NONSPESIFIK FASE ALKILATING, DEKARBASINB. NON SPESIFIK SIKLUS STEROID, ANTIBIOTIK KECUALI BLEOMISINSPESIFIK TERHADAP FASE SELA. FASE G 0 SEMUA KEMOTHY AKAN REFRAKTERB. FASE G 1 L- ASPARAGINASEC. FASE S ANTIMETABOLIT, HIDROKSIUREA, PROKARBAZIND. FASE G 2 BLEOMISIN, ALKALOID TANAMANE. FASE M ALKALOID TANAMAN

GOLONGANSUB GOLONGANO B A TALKILATORMUSTAR NITROGENDERIVAT ETILENAMINALKIL SULFONATNITROSURIASIKLOFOSPAMID, MELFALAN, KLORAMBUSILTIOTEPABUSULFANKARMUSTIN, LOMUSTIN, SAMUSTIN

ANTI METABOLITANALOG PIRIMIDINANALOG PURINANTAGONIS FOLAT5-FU, SITARABIN, 6 AZAURIDIN, FLOKSURIDIN6-MERKAPTOPURUN, 6-TIOGUANIDMETOTREKSATPRODUK ALAMIAHALKALOID VINKAANTIBIOTIK

ENZIMVINBLASTIN, VINKRISTINDAKTINOMISIN, MITOMISIN, ANTRASIKLIN : DAUNORUBISIN & DOXORUBISINL-ASPARAGINASEHORMONADRENOKORTIKOIDPROGESTINESTROGENANDROGENPREDNISONHIDROKSIPROGESTERON, MEGESTROLDIETILSTILBESTEROL, ETINILESTRADIOLTESTOTERON, FLUOKSIMESTERONISOTOP RADIOAKTIFFOSFORYODIUMNATRIUM FOSFATNATRIUM YODIDALAIN-LAINSUBSTITUSI UREADERIVAT METIHIDRAZINHIDROKSIUREAPROKARBAZIN

P E R H A T I A NTOKSISITAS OBAT SST, SALURAN CERNA, SEL FOLIKEL RAMBUTKONTRA 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 / LENGKAPRISIKO LAIN* EFEK IRITASI KULIT* EFEK KARSINOGENIK* EFEK MUTAGENIK

KARNOFSKY SCALE100 %: AKTIFITAS NORMAL, KELUHAN (-), GEJALA PENYAKIT (-)90 %: AKTIFITAS NORMAL, KELUHAN (+), GEJALA PENYAKIT (+)80 %: AKTIFITAS NORMAL DENGAN USAHA, BEBERAPA GEJALA70 %: AKTIFITAS NORMAL (-), DAPAT MENGURUS DIRI SENDIRI60 %: AKTIFITAS NORMAL (-), KADANG PERLU BANTUAN50 %: BANYAK PERLU BNATUAN40 %: PERLU PERAWATAN DAN BANTUAN KHUSUS30 %: TIDAK MAMPU BANGUN, HARUS RAWAT RS20 %: SAKIT BERAT10 %: MENDEKATI AJAL0 %: MENINGGALECOG SCALE0: NORMAL1: GEJALA ADA, TERTOLERANSI2: TAK BISA AKTIFITAS NORMAL, KURANG 50 % BEDREST3: SAKIT BERAT, LEBIH 50 %,BEDREST, MASIH MAMPU BERDIRI4: SAKIT AMAT BERAT, 100 % DITEMPAT TIDUR5: MENINGGAL

PERSIAPAN KEMOTERAPIINFORM CONSENTINFORMASI MANFAAT DAN EFEK SAMPINGPEMERIKSAAN DARAH * HB, > 10 GR%, LEU > 5000 /MM3, TROMB > 100.000/MM3* SGOT, SGPT, UREUM, KREATININ, ASAM URAT4.K/P EKG / EKOKARDIOGRAFI5.DIET MB TKTP6.INFUS NACL 0,9%, DEXTROSE 5 %7.ANTIMUNTAH, METOKLORPAMID / ONDASETRON8.LIHAT PROTAP PENYAKIT9.MONITORING EFEK SAMPING

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