Keganasan Hematologi

SUMARDJO

Leukemia :Malignant and unregulated proliferation

Of haemopoietic or lymphoid cell

It results from a mutation in a single stem cell hemopoietic/ precursor / progeny

Form a clone of leukaemia cells

Overgrowth of certain cell lines

- Replace the bone marrow elements- Interfere with normal marrow function- Invade / collect in other organ such as lymph nodes, liver, spleen &

other tissue- circulate in the peripheral blood

Leukemia classified based on :

1. The disease progresses

Acute : if untreated → lead to death in weeks / month

Chronic : if untreated → lead to death in month or years

2. The stem cell type involved

* Myeloid

* Lymphoid

* Biphenotypic → showing both lymphoid & myeloid differentiation

3. The presence of abnormal/ immature cells (+) :

Bone marrow (+) & peripheral blood (+) : leukemia

Bone marrow (+) & peripheral blood ( - ): Aleukemic leukemia

4. Cytochemistry and immunophenotyping

Keganasan Hematologi

• Leukemia Akut

• Leukemia Kronik CML (chronic myeloid leukemia) CLL (chronic lymphocytic leukemia)

• Limfoma Maligna Hodgkin’s Lymphoma Non Hodgkin’s Lymphoma (NHL)

• Keganasan Sel Plasma Multiple Myeloma (MM)

Leukemia Akut

• Malignansi sel progenitor hematopoetik seri myeloid (acute myeloid leukemia /AML) atau limfosit (acute lympoblastic leukemia/ALL)

• Sel2 imatur tidak mampu berdiferensiasi, berproliferasi tak terkendali Penggantian struktur normal sum2 tulang bone

marrow failure Infiltrasi organ kulit, GIT, meninges (lebih jarang)

• Klinis : durasi gejala pendek fatique, demam, perdarahan, dengan Sitopenia / pansitopenia > 20% blast di sum2 tulang Blast (+) di darah perifer Lekemia akut : TANDA2

BONE MARROW FAILURE+ CIRCULATING BLAST

Pembagian AMLBerdasar Histologi & Biokimia

• M0 : Acute Undifferentiated Leukemia

• M1 : Acute Myeloblastic Leukemia

• M2 : Acute Myeloblastic Leukemia with Differentiation

• M3 : Acute Promyelocytic Leukemia

• M4 : Acute Myelomonocytic Leukemia

• M5 : Acute Monoblastic Leukemia

• M6 : Erythroleukemia

• M7 : Megakaryoblastic Leukemia

AML M3 : APL

• Penelitian sitogenetik pada AML M3 : acute promyelocytic leukemia : pola khas, translokasi kromosom t(15;17) fusion gene baru PML-RARα

• PML-RARα perubahan reseptor retinoic acid pasien blokade diferensiasi sel

• Dosis farmakologis retinoic acid dapat dicoba untuk mengatasi perubahan ini

Pembagian ALLBerdasarkan Immunophenotype• Common

• Early B Lineage

• T Cell

Epidemiologi Lekemia Akut

• ALL merupakan 80% lekemia akut pd anak, puncak insiden usia 3 – 7 tahun

• AML terutama terjadi pd dewasa, median usia pasien 60 tahun, insidensi meningkat dgn bertambah usia

Terapi Leukemia Akut

• Tujuan terapi : kuratif, terutama untuk pasien muda target awal remisi komplet

• Kemoterapi induksi : Daunorubicin - cytarabine (remisi : 70-80%)AML M3 (acute promyelocytic leukemia)

diterapi dgn kemoterapi plus all-trans-retinoic acid (ATRA) (remisi : 90-95%)

• Post remisi :Kemoterapi, transplantasi sum2 tulang

alogenik /autologus

CML

• Gangguan myeloproliferatif, produksi berlebihan sel seri myeloid dgn kemampuan berdiferensiasi yg masih baik. Sum2 tulang berfungsi normal, terutama pd fase awal

• Abnormalitas spesifik : kromosom Philadelphia, hasil translokasi resiprok lengan panjang kromosom 9 dan 22 fusion gen baru Bcr-Abl mencetuskan proliferasi tak terkendali sel dgn membentuk tyrosine kinase

• Klinis : usia pertengahan, splenomegali, lekositosis (> 50.000/mmk) Fase kronik : stabil, 3-6 tahun, respon terapi (+) Fase akselerasi : sitopenia memburuk, respon terapi

(-) Krisis blastik : lekemia akut, tidak respon terapi

Terapi CML

• Mei 2001 : imatinib mesylate (Gleevec) - inhibitor spesifik tyrosine kinase Bcr-Abl : hasil terapi pd pasien yg gagal dgn terapi standar : 95% respon hematologik76% respon sitogenetik (kromosom

Philadelphia - )

• Terapi standar lainHydroxiurea Interferon alfaTransplantasi sum2 tulang alogenik

CLL

• Malignansi clonal limfosit B yg matur, tapi secara imunologis inkompeten tidak respon thd stimulasi antigen

• Perjalanan indolen, proliferasi limfosit B berjalan progresif lambat Mayoritas pasien asimtomatik saat diagnosisTahap lanjut : supresi imun, bone marrow

failure, infiltrasi organ oleh sel BSering dgn anemia / trombositopenia

autoimun

• Klinis : usia tua, dgn isolated lymphocytosis

Staging CLL (Rai System)

• Stage 0 : limfositosis

• Stage I : limfositosis+limfadenopati

• Stage II : organomegali

• Stage III : anemia

• Stage IV : trombositopenia

Terapi CLL

• Observasi pd kasus awal

• Indikasi terapi : simptomatis, atau stage II ke atas

• Terapi terbaru : kombinasi kemoterapi (fludarabin) dan monoclonal antibody (rituximab)

KEGANASAN KEL. LIMFOID

Hodgkin DiseaseEssentials of Diagnosis•Painless lymphadenopathy. •Constitutional symptoms may or may not be present. •Pathologic diagnosis by lymph node biopsy

• Hodgkin disease is divided into several subtypes:

• lymphocyte predominance,

• nodular sclerosis,

• mixed cellularity,

• lymphocyte depletion

The staging (Ann Arbor)

• stage I, one lymph node region involved

• stage II, involvement of two lymph node areas on one side of the diaphragm

• stage III, lymph node regions involved on both sides of the diaphragm

• stage IV, disseminated disease with bone marrow or liver involvement.

• combination chemotherapy using doxorubicin (Adriamycin), bleomycin, vincristine, and dacarbazine (ABVD).

• New shorter and more intensive regimens are being studied, but have not yet proved superior to ABVD.

The prognosis

• stage IA or IIA disease treated by radiotherapy is excellent, with 10-year survival rates in excess of 80%.

• Patients with disseminated disease (IIIB, IV) have 5-year survival rates of 50–60%.

• Poorer results are seen in patients who are older

have bulky disease,

lymphocyte depletion

mixed cellularity on histologic examination.

Non-Hodgkin Lymphomas

Essentials of Diagnosis

• Often presents with painless lymphadenopathy.

• Pathologic diagnosis of lymphoma is made by pathologic examination

classification

Symptoms and Signs

• painless lymphadenopathy

• isolated or widespread

• fever, drenching night sweats, or weight loss.

• The peripheral blood is usually normal

• lymphomas may present in a leukemic phase.

• Bone marrow involvement is manifested as paratrabecular lymphoid aggregates

• I the meninges are involved and malignant cells are found with cerebrospinal fluid cytology.

• The chest radiograph may show a mediastinal mass in lymphoblastic lymphoma.

• Treatment with the anti-CD20 antibody rituximab

• Combinations of rituximab with chemotherapy may also be used.

• Common chemotherapy regimens include fludarabine;

• Combination of cyclophosphamide, vincristine, and prednisone (R-CVP)

• Cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP).

Kepustakaan

• Magiera, H.M., 2004. Myeloproliferative Disorders, in G. Pillot et al., The Washington Manual™ Hematology and Oncology Subspeciality Consult, Lippincott Williams & Wilkins, St Louis

• Waheed, S., 2004. Myelodysplasia, in G. Pillot et al., The Washington Manual™ Hematology and Oncology Subspeciality Consult, Lippincott Williams & Wilkins, St Louis

• Linker, C.A., 2007. Blood, in S.J. McPhee et al., CMDT, 46th Ed, McGraw Hill, New York

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