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% Prostate 10% Colon & rectum 10% Pancreas 5% Leukemia 5% Non-Hodgkin 4% lymphoma Esophagus 4% Liver & intrahepatic 3% bile duct Urinary bladder 3% Kidney 3% All other sites 21% 25% Lung & bronchus 15% Breast 10% Colon & rectum 6% Ovary 6% Pancreas 4% Leukemia 3% Non-Hodgkin lymphoma 3% Uterine corpus 2% Multiple myeloma 2% Brain/ONS 24% All other sites Lung cancer is, by far, the most common fatal cancer in men (32%), followed by prostate (10%), and colon & rectum (10%). In women, lung (25%), breast (15%), and colon & rectum (10%) are the leading sites of cancer death. Men 290,890 Women 272,810 ONS=Other nervous system. Source: American Cancer Society, 2004.

DISTRIBUSI LEUKEMIA DI RSKD (1993-2000) Agus Kosasih et al.

PATHOGENESIS OF HEMATOLOGIC MALIGNANCY

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 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 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

Chronic lymphocytic 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 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 : 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

TERIMA KASIH