2 nd step do Bone Marrow Study If possible both the aspiration and

Transcription

1 Blood Malignancies-I Prof. Herman Hariman,SpPK a (KH). Ph.D.(U.K) Prof. Dr. Adikoesoema Aman, SpPK (KH) Dept. Clinpath, FK-USU

2 First do the Full Blood Count Hb, WBCS, Platelets Morphology!! Such as blasts, abnormal mononuclears, ordinary cells which shows abnormal appearances Unexplained drop of platelet numbers Unexplained drop of Hb Unexplained drop or increase of WBCs Cell Counter

3 2 nd step do Bone Marrow Study If possible both the aspiration and Aspiration Biopsy Cytogenetics biopsy Immunophenotyping Tissue typing (HLA)

4 DASAR DIAGNOSA LEUKEMIA MORFOLOGI CELL RUTIN STAINING SPESIAL STAINING ( SITOSTAINING )

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6 ISLAM aspiration needle

7 ISLAM biopsy needle set

8 Cytostaining Sudan Black (SBB), Myeloperoxidase (MPO), neutrophil alkaline phosphatse p They are oudated by immunophenotyping (flowcytometer) and cytogenetics (qrt- PCR) especially in the implementation of WHO classification of blood malignancies

9 MPO stain, myeloblast but negative for neutrophil

10 Sudan Black B

11 Flowcytometer together with PCR can be used for cytogenetics

12 KLASIFIKASI LEUKEMIA FAB ( MIC ) WHO ( 1997 ) The European Association of Pathologist And the Society for Hematopathology -Morfologi -Lymphoid Neoplasma -ImmunophenotypingI h t i -Myeloid Neoplasma -Cytogenetic -Histiocytic Neoplasma -Mast Cell Neoplasma

13 IMMUNOPHENOTYPING ( IMMUNOLOGI MARKERS ) SEL : DEFINISI : Pertanda Immunologi dari struktur / antigen permukaan sel baik sel normal maupun sel Leukemia

14 Immunophenotyping ( Cluster Differentiation ) 1 st International lworkshop and Humen Leucocyte Differentiation Antigen ( 1982 ) di Paris Nomenclature CD 151 CD 5 th Boston Workshop ( 1993 ) Update CD 6 th Workshop on HLDA ( Tadamatsu Kishimoto dari Osaka University Medical School ) 1000 CD

15 FAB Classification of myeloid Chronic myeloproliferative lif diseases malignancies Myelodysplastic syndromes Acute myeloid leukaemias

16 W.H.O Classification of Myeloid Malignancies Chronic myeloproliferative diseases Myelodysplastic/myeloproliferative diseases Myelodysplastic syndromes Acute myeloid leukaemias

17 Classification of myeloid malignancies FAB Chronic myeloproliferative lif diseases Myelodysplastic syndromes Acute myeloid leukaemias WHO Chronic myeloproliferative lif diseases Myelodysplastic/myelop roliferative diseases Myelodysplastic syndromes Acute myeloid leukaemias

18 Chronic Myeloproliferative Disorders FAB Chronic myelogenous leukemia (CML) Agnogenic myeloid metaplasia with myelofibrosis i (MF) (Idiopathic myelofibrosis) Polycythemia vera (EV) Essential thrombocytemia (ET) WHO CML Ph+: t(9;22)(qq34;q11), BCR/ABL Chronic neutrophilic leukemia Chronic eosinophilic leukemia/hypereosinophilic i hili syndrome Chronic idiopathic myelofibrosis Polycythemia vera Essential thrombocytemia

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20 (French American British) F.A.B Based on MORPHOLOGY > 30% blasts = ACUTE LEUKAEMIA < 5% = normal or Chronic Leukaemia 6-29% = MYELODYSPLASTIC SYNDROME with the exception of Erythroleukaemia can be 6-29% blasts but the blast/nec ratio > 30%

21 CHRONIC MYELOPROLIFERATIVE DISODERS CML Ph+: t(9;22)(qq34;q11), q ) BCR/ABL Chronic neutrophilic leukemia Chronic eosinophilic leukemia/hypereosinophilic syndrome Chronic idiopathic myelofibrosis Polycythemia vera Essential thrombocytemia

22 Laboratory tests FBCs: leucocytosis (>100 x 109/l) with immature neutrophil (myelocytes y +metamyelocytes) Basophilia Neutrophil Alk Phosphatase: reduced BMP: Ph 1 and BCR/Abl oncogene + do HLA typing

23 New Chimeric Fusion Protein BCR/Abl oncogene BCR/Abl TYROSINE KINASE PROLIFERATIVE EFFECT ARREST OF DIFFERENTIATION ARREST OF APOPTOSIS

24 CML The most important change is, that only the The most important change is, that Ph+ cases are called CML by the WHO. The Ph- cases (which show myelodysplastic signs, and are known to have significantly worse prognosis) i) are called lldacml (t (atypical lcml) CML), and belong to the newly created myelodysplastic / myeloproliferative group. The acml term is somewhat misleading, because it is not CML at all, but it was kept, having no better alternative.

25 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.

26 CML accelerated phase, leukocytosis with abnormal lobulation nuclei blasts less 20%

27 CML BLASTIC CRISIS

28 Hypereosinophilic syndrome/cel

29 Idiopathic Myelofibrosis

30 Myelodysplastic / Myeloproliferative Disorders Atypical myelogenous leukemia (acml) same morphology, Ph (-)ve, BCR/Abl (+)ve Chronic myelomonocytic leukemia (CMML) same morphology with > 20% monocytes Juvenile myelomonocytic leukemia (JMML) same morphology but in children < 2 ys old CMML belonged to the MDS in the FAB classification. About one half of the cases show proliferative, the other dysplastic signs, but it looks like these are just different forms of the same disease.

31 MYELODYSPLASTIC SYNDROME Refractory anemia (RA) Refractor anemia with ringed sideroblasts (RARS) Refractory cytopenia with multilineage dysplasia (new) Refractory anemia with excess blasts (FAB: RAEB) 5q- syndrome (new) unclassifiable (new)

32 No granules PSEUDO-PELGER (no granules) as sign of dysmyelopoiesis

33 DYSERYTHROPOIESIS

34 DYSMEGAKARYOPOIESIS

35 Ring Sideroblast

36 RCMD

37 Refractory Cytopenia with Multilineage Dysplasia (RCMD)

38 Refractory Cytopenia with Multilineage Dysplasia (RCMD)

39 RAEB-1

40 RAEB-2

41 BELGIAN ANAEMIA 5q- syndrome

42 ACUTE MYELOID LEUKAEMIA AML with recurrent cytogenetic translocations AML with t(8;21)(q22;q22) AML1/CBFalpha/ETO Acute promyelocytic leukemia:aml with t(15;17)(q22;q12) and variants PML/RARalpha AML with abnormal bone marrow eosinophils inv(16)(p13;q22) vagy t(16;16)(p13;q22) CBFbeta/MYH1 AML with 11q23 MLL abnormalities

43 Acute myeloid Leukaemia (continued) AML with multilineage dysplasia With prior MDS Without prior MDS AML with myelodysplastic y syndrome, therapy related Alkylating agent related Epipodophyllotoxin related AML not otherwise categorized AML minimally differentiated AML without maturation AML with maturation Acute myelomonocytic leukemia Acute monocytic leukemia Acute erythroid leukemia Acute megakaryocytic leukemia Acute basophilic leukemia Acute panmyelosis with myelofibrosis

44 A.M.L-M1

45 A.M.L-M2; 25% of M2 may contain t-8:21

46 AML-M3 hypergranular can be found in t-15:17

47 M3 folding nuclei

48 INV(16)/AMLM4Eo

49 AML-M5

50 AML-M6

51 AML-M7

52 AML de Novo or secondary Investigation of risk factors Good Risk Standard/ Poor Risk t(8;21), t(15;17) IntermediateRisk Relapsed Inv(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 FLA ±G-CSF ±G-CSF Course-4 BMT Course-4 ±ATRA ±ATRA Course-5 BMT Course-5 Off BMT Consolidation

53 Cytogenetic, the most significant factors Good Risk Standard/ Poor Risk t(8;21), t(15;17) IntermediateRisk Relapsed Inv(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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55 THANK YOU