Post on 05-Jul-2018
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Blood Malignancies-IBlood Malignancies-I
Prof. Herman Hariman S PK KH . Ph.D. U.KProf. Herman Hariman S PK KH . Ph.D. U.K
Prof. Dr. Adikoesoema Aman, SpPK (KH)Prof. Dr. Adikoesoema Aman, SpPK (KH)
De t. Clin ath FKDe t. Clin ath FK--USUUSU
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Hb, WBCS, PlateletsHb, WBCS, Platelets
orp o ogy uc as asts, a norma mononuc ears,orp o ogy uc as asts, a norma mononuc ears,
ordinary cells which shows abnormal appearancesordinary cells which shows abnormal appearances
Unex lained dro of latelet numbersUnex lained dro of latelet numbers
Unexplained drop of HbUnexplained drop of Hb
Unexplained drop or increase of WBCsUnexplained drop or increase of WBCs
Cell Counter
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ndnd
If possible both the aspiration andIf possible both the aspiration and
opsyopsy
BiopsyBiopsy
CytogeneticsCytogenetics
Immuno henot inImmuno henot in Tissue typing (HLA)Tissue typing (HLA)
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DASAR DIAGNOSA LEUKEMIA
MORFOLOGI CELL
RUTIN STAINING
SPESIAL STAINING
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ISLAM biopsy needle set
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CytostainingCytostaining
Sudan Black (SBB), MyeloperoxidaseSudan Black (SBB), Myeloperoxidase
MPO neutro hil alkaline hos hatseMPO neutro hil alkaline hos hatse
They areThey are oudatedoudated by immunophenotyping by immunophenotyping
--
PCR) especially in the implementation ofPCR) especially in the implementation of
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MPO stain, myeloblast but negative for neutrophil
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Sudan Black B
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Flowcytometer together with PCR can be used for cytogenetics
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KLASIFIKASI LEUKEMIAKLASIFIKASI LEUKEMIA
WHO ( 1997 )WHO ( 1997 )
The Euro ean Association of Patholo istThe Euro ean Association of Patholo ist
And the Society for HematopathologyAnd the Society for HematopathologyFAB ( MIC )
-Lymphoid Neoplasma-Morfologi
-
-Histiocytic Neoplasma
- mmunop eno yp ng
-Cytogenetic
-Mast Cell Neoplasma
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( IMMUNOLOGI MARKERS ) SEL :( IMMUNOLOGI MARKERS ) SEL :
DEFINISI :DEFINISI :
permukaan sel baik sel normal maupun selpermukaan sel baik sel normal maupun sel
LeukemiaLeukemia
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Immunophenotyping
( Cluster Differentiation )1s Internat ona Wor s op an Humen Leucocyte
Differentiation Antigen ( 1982 ) di Paris
Nomenclature CD 151 CD
5th Boston Workshop ( 1993 ) Update CD
6th Workshop on HLDA( Tadamatsu Kishimoto dari Osaka University Medical School )
1000 CD
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malignancies
malignancies
FABFAB
ChronicChronic
mye opro era vemye opro era vediseasesdiseases
MyelodysplasticMyelodysplasticsyndromessyndromes
Acute myeloid Acute myeloid
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. .
Myeloid Malignancies
. .
Myeloid Malignancies
Myelodysplastic/myeloproliferativeMyelodysplastic/myeloproliferative
Myelodysplastic syndromesMyelodysplastic syndromes
Acute myeloid leukaemias Acute myeloid leukaemias
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malignancies
malignancies
FABFAB
ChronicChronic
WHOWHO
ChronicChronic
mye opro era vemye opro era vediseasesdiseases
mye opro era vemye opro era vediseasesdiseases
M elod s lastic/m eloM elod s lastic/m elo
MyelodysplasticMyelodysplastic
roliferative diseasesroliferative diseases
MyelodysplasticMyelodysplastic
syndromessyndromes
Acute myeloid Acute myeloid
syn romessyn romes
Acute myeloid Acute myeloid
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Disorders
Disorders FABFAB
Chronic myelogenousChronic myelogenousleukemia (CML)leukemia (CML)
WHOWHO
CML Ph+: t(9;22)(qq34;q11),CML Ph+: t(9;22)(qq34;q11),BCR/ABLBCR/ABL
Agnogenic myeloid Agnogenic myeloidmetaplasia withmetaplasia with
Chronic neutrophilicChronic neutrophilicleukemialeukemia
Chronic eosinophilicChronic eosinophilicmye o ros smye o ros s(Idiopathic myelofibrosis)(Idiopathic myelofibrosis)
eu em a ypereos nop ceu em a ypereos nop csyndromesyndrome
Chronic idiopathicChronic idiopathic
Polycythemia vera (EV)Polycythemia vera (EV)
Essential thrombocytemiaEssential thrombocytemia
Polycythemia veraPolycythemia vera
Essential thrombocytemiaEssential thrombocytemia
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(French American British) F.A.B(French American British) F.A.B
Based on MORPHOLOGYBased on MORPHOLOGY
==
< 5% = normal or Chronic Leukaemia< 5% = normal or Chronic Leukaemia
-- ==
SYNDROME with the exception ofSYNDROME with the exception of
ryt ro eu aem a can eryt ro eu aem a can e -- asts utasts ut
the blast/NEC ratio > 30%the blast/NEC ratio > 30%
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CHRONICCHRONIC
MYELOPROLIFERATIVEMYELOPROLIFERATIVE
CML Ph+: t(9;22)(qq34;q11), BCR/ABLCML Ph+: t(9;22)(qq34;q11), BCR/ABL
Chronic neutrophilic leukemiaChronic neutrophilic leukemia
Chronic eosino hilicChronic eosino hilic
leukemia/hypereosinophilic syndromeleukemia/hypereosinophilic syndrome
Chronic idiopathic myelofibrosisChronic idiopathic myelofibrosis Polycythemia veraPolycythemia vera
Essential thromboc temiaEssential thromboc temia
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Laboratory testsLaboratory tests
FBCs: leucocytosis (>100 x 109/l) withFBCs: leucocytosis (>100 x 109/l) with
immature neutro hil m eloc tesimmature neutro hil m eloc tes
+metamyelocytes)+metamyelocytes)
Neutrophil Alk Phosphatase: reducedNeutrophil Alk Phosphatase: reduced
:: an oncogene + oan oncogene + oHLA typingHLA typing
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BCR/Abl oncogene
BCR/Abl oncogene
PROLIFERATIVE EFFECTPROLIFERATIVE EFFECT
ARREST OF DIFFERENTIATIONARREST OF DIFFERENTIATION
ARREST OF APOPTOSISARREST OF APOPTOSIS
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CMLCML The most important change is, thatThe most important change is, that only theonly the
Ph+ cases are called CMLPh+ cases are called CML b the WHO. b the WHO.TheThe PhPh-- casescases (which show myelodysplastic signs,(which show myelodysplastic signs,and are known to have significantly worseand are known to have significantly worse prognos s are ca e prognos s are ca e aa a yp ca , ana yp ca , an belong to the newly created belong to the newly created myelodysplastic /myelodysplastic /
m elo roliferative roum elo roliferative rou . The aCML term is. The aCML term issomewhat misleading, becausesomewhat misleading, because it is not CMLit is not CML atatall, but it was kept, having no better alternative.all, but it was kept, having no better alternative.
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Chronic phase CML Low power view of this bone marrow aspirate reveals
an increased ME ratio. Eosinophils and larger immature myeloid elements
are also evident.
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CML accelerated phase, leukocytosis with abnormal lobulation nuclei blasts less 20%
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CML BLASTIC CRISIS
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Hypereosinophilic syndrome/CEL
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Idiopathic Myelofibrosis
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Disorders
Disorders
Atypical myelogenous leukemia (aCML) Atypical myelogenous leukemia (aCML) samesamemorphology, Ph (morphology, Ph (--)ve, BCR/Abl (+)ve)ve, BCR/Abl (+)ve
same morphology with > 20% monocytessame morphology with > 20% monocytes
Juvenile myelomonocytic leukemia (JMML)Juvenile myelomonocytic leukemia (JMML)same morp o ogy ut n c ren < ys osame morp o ogy ut n c ren < ys o
..half of the cases show proliferative, the other dysplastic signs,half of the cases show proliferative, the other dysplastic signs,but it looks like these are just different forms of the samebut it looks like these are just different forms of the samedisease.disease.
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SYNDROME
SYNDROME
Refractory anemia (RA)Refractory anemia (RA)
e rac or anem a w r nge s ero as se rac or anem a w r nge s ero as s(RARS)(RARS)
Refractor c to enia with multilinea eRefractor c to enia with multilinea edysplasiadysplasia (new)(new)
Refractory anemia with excess blasts (FAB:Refractory anemia with excess blasts (FAB:
5q5q-- syndromesyndrome (new)(new)
unclassifiableunclassifiable newnew
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No granules
PSEUDO-PELGER (no granules) as sign of dysmyelopoiesis
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DYSERYTHROPOIESIS
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Rin Sideroblast
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RCMD
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Refractory Cytopenia with Multilineage Dysplasia (RCMD)
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Refractory Cytopenia with Multilineage Dysplasia (RCMD)
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RAEB-2
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BELGIAN ANAEMIA 5q- syndrome
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ACUTE MYELOID LEUKAEMIA ACUTE MYELOID LEUKAEMIA AML with recurrent cytogenetic translocationsAML with recurrent cytogenetic translocations
AML with t(8;21)(q22;q22) AML1/CBFalpha/ETO AML with t(8;21)(q22;q22) AML1/CBFalpha/ETO
t(15;17)(q22;q12) and variants PML/RARalphat(15;17)(q22;q12) and variants PML/RARalpha
AML with abnormal bone marrow eosinophils AML with abnormal bone marrow eosinophilsinv(16)(p13;q22) vagy t(16;16)(p13;q22)inv(16)(p13;q22) vagy t(16;16)(p13;q22)CBFbeta/MYH1CBFbeta/MYH1
AML with 11 23 MLL abnormalities AML with 11 23 MLL abnormalities
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(continued)
(continued) AML with multilineage dysplasiaAML with multilineage dysplasia
With prior MDSWith prior MDS
Without prior MDSWithout prior MDS
AML with myelodysplastic syndrome, therapy relatedAML with myelodysplastic syndrome, therapy related
Alkylating agent related Alkylating agent relatedEpipodophyllotoxin relatedEpipodophyllotoxin related
AML not otherwise categorizedAML not otherwise categorized
AML minimally differentiated AML minimally differentiated
AML without maturation AML without maturation
AML with maturation AML with maturation
Acute myelomonocytic leukemia Acute myelomonocytic leukemia
Acute monocytic leukemia Acute monocytic leukemia
Acute erythroid leukemia Acute erythroid leukemia
Acute megakaryocytic leukemia Acute megakaryocytic leukemia
Acute basophilic leukemia Acute basophilic leukemia
Acute panmyelosis with myelofibrosis Acute panmyelosis with myelofibrosis
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A.M.L-M1
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A.M.L-M2; 25% of M2 may contain t-8:21
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AML-M3 hypergranular can be found in t-15:17
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M3 folding nuclei
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AML-M6
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AML-M7
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AML de Novo or secondary
Investigation of risk factors
Good Risk Standard/ Poor Risk
t(8;21), t(15;17) IntermediateRisk Rela sedInv(6) w/wo other No favourable nor unfavourable >15% blasts after C1
Cytogenetic cytogenetic abnormalities -5, -7, abn(3q), complex
abnormalities 5-15% blasts after C1 genetic abnormalities
Induction-C1 Induction-C1
Induction-C2 Induction-C2
2 Courses
Consolidation Consolidation ADE FLAG-CSF G-CSF
Course-4 BMT Course-4 ATRA ATRA
Course-5 BMT Course-5 Off BMT Consolidation
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Cytogenetic, the most significant factors
Good Risk Standard/ Poor Risk
t(8;21), t(15;17) IntermediateRisk Rela sedInv(6) w/wo other No favourable nor unfavourable >15% blasts after C1
Cytogenetic cytogenetic abnormalities -5, -7, abn(3q), complex
abnormalities 5-15% blasts after C1 genetic abnormalities
CN-AML (Cytogenetically Normal)
50% patients are assigned
In the intermediate group
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