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Leukemia

Bagian Ilmu Kesehatan Anak FK UNSRAT/RSU. Prof. Dr. R.D. Kandou-Manado

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Proliferasi maligna (tak terkendali)dari 1 atau lebih sel hemopoesisdalam SUTUL

Sel hemopoesis yang lain terdesak /aplasia

Muncul gejala klinik

Fatal

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nsiden

Leukemia

41% of all malignancies

In children < 15 yrs 4.1 per 100.000 children

ALL 77%

AML 11%

CML 2-3%JCML 1-2%

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Etiologi Belum diketahui

Ada hubungan (epidemiologik) Faktor genetik

Kembar identik

Sidroma Down

Anemia Fanconi

Sindroma Bloom

Kelainan Kongenital defisiensi imun Ataxia teleangiektasi

Sindroma Wiskott-Aldrich

Agamaglobinemia

Penyakit imunitas selular

Karsinogen Radiasi

Bahan kimia

Virus Retrovirus

Human T Cell Leukemia Virus (HTLV)

Hormon Growth Hormon

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Perubahan kromosom

Faktor intrinsik (Host)

Faktor ekstrinsik (lingkungan)

Melibatkan bidang Genetik

Biologi molekuler

Virologi imunologi

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Penyebaran

Kelenjar mediastinal

Susunan saraf pusat

Testis Ovarium

Tulang

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Gambaran Klinik

Akibat aplasia sel hemopoesis

Perdarahan Mudah infeksi

Anemia

Akibat proliferasi limfopoesis

Pembesaran hati / limpa

Limfadenopati Gejala lain

Gangguan SSP Infiltrasi sel leukemia

Perdarahan

Infeksi

Hipertrofi ginggiva

Nyeri tulang / sendi

Disseminated Intravascular Coagulation

Sindrom vena cava

Tumor mediastinum

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Laboratorium

Lekosit normal atau meningkat, bisaleukopenia

Trombositopenia

Sumsum tulang

Hiperselular

Monoton sel blas yang mengalamikeganasan

LDH, asam urat meningkat

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Diagnosis

Penting untuk mengetahui tipebentuk akut LLA atau LNLA

Morfologi

Histokimia

klasifikasi

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Pembagian leukemia

Acute leukemia (97%)

Acute lymphoblastic leukemia (ALL) 75%

Acute Non lymphoblastic Leukemia (ANLL) 20 %

Acute Undifferentiated leukemia (AUL) < 0.5%

Acute mixed lineage leukemia (AMLL My+ALL 6%

Ly+AML 17%

Chronic Leukemia ( 3%)

Philadelphia chromosome positive (Ph1

positive) Juvenile chronic myelogenous leukemia (JCML)

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Leukemia Classification

Morphology

Cytochemical

Immuno-phenotyping Cytogenetic

Molecular

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Cytologic features of the lymphoblastic leukemia

Cytologic fatures L1 L2 L3

Cell size Small cellspredominate

Large, heterogenousin size

Large andheterogenous

Nuclear chromatin Homogenous in anyone case

Variable,heterogeneous in

any one case

Finely stippled andhomogenous

Nuclear shape Regular, occasionalcleftingorindentation

Irregular, clefting,indentation common

Regular, oval toround

nucleoli Not visible, small,inconspicious

One or morepresent, often large

Prominent, one ormore vesicular

Amount ofcytoplasm

Scanty Variable,oftenmoderatelyabundant

Moderatelyabundant

Basophilia ofcytoplasm

Slight or moderate,rarely intense

Variable, deep insome

Very deep

Cytoplasmicvacuolization

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FAB CLASSIFICATION

ALL

L1 L2 L3

ANLL

M0 lymphoblasticmorphology,negative MPO &Sudan black, despitepositivity of myeloid antigen

M1 without maturation

M2with differentiation M3promyelocitic

M4 myelocytic and monocytic

M5 monocytic

M6 erythro leukemia M7 Megakarioblastic

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Acute Lymphoblastic leukemia

3 tipe : L1, L2, L3

Tipe L1

Paling sering

Prognosis baik (favourable)

Tipe L2, L3

Jarang

Ganas (Unfavourable)

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Acute Non Lymphoblastic Leukemia

8 tipe : M0M7

Semua tipe ganas (Unfavourable)

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Cytochemical Features of the Acute LeukemiaALL ANLL

Staining Reaction AML AMML Erythroleukemia MegakaryoblasticLeukemia

Nonenzymatic

PAS Present as coarse

granules or blocks

in a variable

number of cells

Negative or

diffusely

positive

Negative or fine

granulation

Strongly positive

granular

Positive or negative

Sudan Black Negative positive positive positive Negative

Enzymatic

peroxides negative positive Usually negative positive negative

Alk phophatase normal low High Normal or high negative

Esterases

Naphthol AS-D

chloroacetate

Negative positive negative negative negative

Naphthol AS-D

Acetate

Negative or weakly

positive

positive Strongly positive Weakly positive Positive or negative

Naphtyl acetate Negative Negative Strongly positive Strongly positive Positive or negative

Acid Phosphatase Positive in T -ALL Negative negative negative positive

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Prognostic factors in ALL

Age

White blood cell count

Immunophenotype Karyotype

Molecular biology

Drug resistance Initial responses to therapy

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Faktor prognostik ALL pada anak

Faktor Baik Jelek

Demografiumur

Kelamin

Sebaran sel leukemik

Jumlah leukosit

Adenopati

Penyebaran ke SSP

Hemoglobin

Jumlah trombosit

Morfologi

Limfoblast

Ph Kromosom

Imunologis

Imunoglobin

Surface marker

Respons terhadap pengobatan induksi

(hari ke 14)

2 9 tahun

Perempuan

50.000/mm3

Ada

Ada

>10 gr%

25%

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Stratification of therapy in ALL protocol

Standard risk

High risk

B cell

WBC < 50.000

Age 1 9 yr

No Med mass

No CNS No B Cell ALL

o all other except

o FAB L3 = B Cellspecial protocol

B cell protocol

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Referral Centre of North East Indonesia region

Province Population 14 yrs EstimationLeukemia Cases

NorthSulawesi

2,012,098 603,629 25

Gorontalo 887,000 266,100 11

CentralSulawesi

2,218,435 665,530 27

Maluku 1,205,539 361,661 15

North Maluku 785,059 235,517 10

Papua 2,220,934 666,280 27

Total 9,329,065 2,798,717 115

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Pengelolaan

Riwayat penyakit Pengobatan yang pernah diperoleh

Pekerjaan

Radiasi

Exposure terhadap bahan kimia

Pemeriksaan fisik Suhu

Kel. Getah bening

SSP

Daerah infeksi kulit, mulut / gusi, paru, peri anal

Pemeriksaan darah tepi

Pem. SUTUL Pem.Elektrolit, asam urat, fungsi ginjal/hati, hemostatis

Cairan SSP

Foto toraks

Gol.darah penderita dan keluarga

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Pengobatan

Tujuan

Mencapai keadaan bebas penyakit(remisi) untuk waktu yang panjang

Faktor yang berperan

K.U penderita

Usia

Jenis leukemia

Jumlah leukosit sebelum diobati

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Tahapan pengobatan

Induksi Menurunkan jumlah sel leukemia serendah

mungkin (1 1,5 bulan)

Konsolidasi Membunuh sel kanker yang ada pada daerah

sanctuary site (1 3 bln)

Maintenance Menjaga agar sel leukemia tidak muncul lagi

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Alternatif pengobatan

Pengobatan sitostatika konvensional

Setelah remisi dilanjutkan dengantransplantasi sumsum tulang

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