LIMFOMA MALIGNUM NON HODGKIN IRZA WAHID SUBAGIAN HEMATOLOGI & ONKOLOGI FK UNAND - RS DR M DJAMIL PADANG
LIMFOMA MALIGNUMNON HODGKIN
IRZA WAHIDSUBAGIAN HEMATOLOGI & ONKOLOGI FK UNAND - RS DR M DJAMIL PADANG
DEFINISISekelompok keganasan primer limfosit yang dapat berasal dari limfosit B, limfosit T dan kadang ( amat jarang ) berasal dari sel NK ( natural killer ) yang berada dalam sistim limfe, sangat heterogen baik tipe histologis, gejala, perjalanan klinis, respon terapi maupun prognosis
Non-Hodgkin’s Lymphoma
• Non-Hodgkin’s lymphomas (NHL) are a heterogeneous group of malignant lymphomas. There are many different subtypes, every few years the classification is updated. Today, morphology, immunophenotype, molecular, cytogenetics, and other techniques are used for diagnosis.
• Treatment generally depends on the aggressiveness of the disease (indolent, aggressive, or very aggressive)
• Current ICD-9-CM diagnosis code range 200.0_ – 200.8_ and 202.0_ – 202.9_
Lymphoma and Multiple Myeloma2004 U.S.
Malignancy New Cases Deaths
All Cancer s 1,368,030 563,700Non-Hodgkin’s
Lymphoma 54,370 19,410Hodgkin’s Disease 7,880 1,320
CA Cancer J Clin 2004; 54:8-29
Former First Lady
Jacqueline Kennedy Onassis
King Hussein of Jordan
Television star, The A-Team. Sylvester Stallone's adversary in "Rocky III.”
“Mr. T”(Lawrence Tureaud)
ETIOLOGI DAN FAKTOR RISIKO
Etiologi pasti tidak diketahui beberapa faktor risiko :
•Paparan lingkungan dan pekerjaan seperti peternak pekerja hutan / pertanian yang disebabkan paparan herbisida dan pelarut organic serta paparan ultraviolet
* Diet tinggi lemak hewani dan merokok
Etiology of NHL
• Immune suppression– congenital (Wiskott-Aldrich)– organ transplant (cyclosporine)– AIDS– increasing age
• DNA repair defects– ataxia telangiectasia– xeroderma pigmentosum
Etiology of NHL• Chronic inflammation and antigenic stimulation
– Helicobacter pylori inflammation, stomach– Chlamydia psittaci inflammation, ocular adnexal
tissues– Sjögren’s syndrome
• Viral causes– EBV and Burkitt’s lymphoma– HTLV-I and T cell leukemia-lymphoma– HTLV-V and cutaneous T cell lymphoma– Hepatitis C
KLASIFIKASI
* Penggolongan histologi LNH merupakan masalah yang rumit dan sukar •Perkembangan terakhir klasifikasi yang banyak dipakai adalah formulasi praktis •( working formulation = WF 1982 ) dan Revised Europe – American Classification of Lymphoid Neoplasms / World Health Organization ( REAL / WHO 1997)
WHO/REAL Classification of Lymphoid NeoplasmsB-Cell Neoplasms
Precursor 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 lymphoma‡
Splenic 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 lymphoma
Mediastinal large B-cell lymphomaPrimary effusion lymphoma†
Burkitt’s lymphoma/Burkitt cell leukemia§
T and NK-Cell NeoplasmsPrecursor 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 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 γδ T-cell lymphoma*Subcutaneous panniculitis-like T-cell lymphoma*Mycosis fungoides/Sézary 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 typeHodgkin’s Lymphoma (Hodgkin’s Disease)
Nodular lymphocyte predominance Hodgkin’s lymphomaClassic Hodgkin’s lymphoma
Nodular sclerosis Hodgkin’s lymphoma (grades 1 and 2)Lymphocyte-rich classic Hodgkin’s lymphomaMixed cellularity Hodgkin’s lymphomaLymphocyte depletion Hodgkin’s 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
Klasifikasi WF ( 1982 )
Low grade malignancySmall lymphocytic / plasmacytoid
Follicular, predominantly small cleaved cellFollicular, mixed small cleaved and large cell
Intermediete grade malignancyFollicular, predominantly large cell
Difuse, small cleaved cellDiffuse, mixed small and large cell
High grade malignancy Large cell, immunoblastic
Lymphoblastic Small, non cleaved cell
PENDEKATAN DIAGNOSTIK
1. Anamnesis
Umum Pembesaran KGB atau organ
BB menurun ≥ 10 % dalam waktu 3 bulanDemam tinggi ≥ 38 C ≥ 1 minggu tanpa sebab
Keringat malamKeluhan anemia
Keluhan organ ( seperti lambung, nasofaring )Penggunaan obat ( Diphantoine )
KhususPenyakit autoimun ( SLE, syogren, reuma )
Kelainan darahInfeksi ( Toxoplasmosis, mononucleosis, tuberculosis, lues, cakar kucing
2. Pemeriksaan fisik
* Pembesaran KGB
•Kelainan / pembesaran organ
•* Performance status : WHO, Karnofsky
3. Pemeriksaan penunjang
Laboratorium* Rutin Darah perifer lengkap ( DPL ), Gambaran darah tepi ( GDT )
Urine lengkap* Kimia Klinik
* Imunophenotyping parafin panel CD 20, CD 3
Radiologi* Foto torak CT Scan torak
* USG Abdomen CT Scan abdomen* Limfografi
Biopsi KGB
BMP & biopsi SST
Diagnosis of NHL• Excisional biopsy is preferred to show nodal
architecture (follicular vs diffuse).• Immunohistochemistry to confirm cells are
lymphoid– LCA (leukocyte common antigen)– Monoclonal staining with Ig or Ig
• Flow cytometry:– CD 19, CD20 for B cell lymphomas– CD 3, CD 4, CD8 for T cell lymphomas
Diagnosis of NHL
• Chromosome changes– 14;18 translocation in follicular lymphoma
• bcl-2 oncogene
– t(8;14), t(2;8), t(8;22) in Burkitt’s lymphoma
• c-myc oncogene
– t(11;14) in mantle cell lymphoma• cyclin D1 gene
STADIUM ( Ann Arbor Modifikasi Cotswald )* 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.3 Pembesaran 3 regio KGB II E Pembesaran 1 regio KGB + 1 extralimfatik tidak difus
* Stadium III Pembesaran KGB regional 2 sisi diafragma
* Stadium IV Jika mengenai minimal 1 organ extralimfatik, difusA : bila tanpa gejala sistemik, B : dg gejala sistemikX : bila ada bulky mass ( > 1/3 torak, > 10 cm untuk KGB
PENATALAKSANAAN1. Radioterapi
2. Radioterapi + Kemoterapi3. Kemoterapi
Generasi Pertama
Cyclophosphamide 750 mg IV hari 1Oncovin 1,4 mg IV hari 1
Adriamisin 50 mg IV hari 1Prednison oral
4X20mg hari 1– 5, 3 X 20 mg hr ke 6, 2 X 20 mg hr ke 7, 1 X 20 mg hr ke 8 siklus diulangi setiap 21 hari selama 6 siklus
Generasi dua* M-Bacod, MOPP, COPBLAM, CAP-BOP
Generasi tiga* MACOP B, COPBLAM III, COPBLAM IV, CHOP-Bleo/CMED
relaps : salvage terapi
Treatment Options:Indolent lymphomas
FOLLICULAR LYMPHOMA• 10-15% in Stage I or II
– potentially curable– local radiotherapy
• 85-90% Stage III or IV– incurable– treatment does not prolong survival
Reasons to Treat in Advanced Indolent Lymphomas
• Constitutional symptoms• Anatomic obstruction• Organ dysfunction• Cosmetic considerations• Painful lymph nodes• Cytopenias
Treatment Options inAdvanced Indolent Lymphomas
• Observation only.• Radiotherapy to site of problem.• Systemic chemotherapy
– oral agents: chlorambucil and prednisone– IV agents: CHOP, COP, fludarabine, 2-CDA.
• Antibody against CD20: Rituxan, Bexxar, Zevalin.
• Stem cell or bone marrow transplant.
CHOP Chemotherapy
• Cyclophosphamide (Cytoxan)• Hydroxydaunorubicin
(Adriamycin)• Oncovin (vincristine)• Prednisone
Treatment Options:Aggressive Lymphomas
Aggressive• Diffuse large cell lymphoma, large cell
anaplastic lymphoma, peripheral T cell lymphoma.
Very Aggressive• Burkitt’s lymphoma and lymphoblastic
lymphoma.
Treatment Options for Early Stage Aggressive Lymphomas
• Often in Stage I or II– potentially curable– disseminates through bloodstream early– must use systemic chemotherapy
• CHOP x 6 cycles• CHOP x 3 cycles followed by radiotherapy
Treatment Options for Advanced Stage Aggressive Lymphomas
• Systemic chemotherapy– CHOP (± Rituxan for over 70 age group)
• ± Intrathecal chemotherapy – AIDS patients and CNS involvement
• ± Radiotherapy– Spinal cord compression, bulky disease
PROGNOSIS
LOW GRADE : 6 – 7 YRS (MED SURVIVAL)
AGGRESSIVE : 3 – 4 YRS (MED SURVIVAL)
RAPIDLY PROGRESSIVE60 % (5-YRS SURVIVAL)
T E R I M A K A S I H