Keganasan Hematologi
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Transcript of Keganasan Hematologi
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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