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MYELOPROLIFERATIVE DISEASES By DR. FATIMA AL-QAHTANI CONSULTANT HAEMATOLOGIST.

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Presentation on theme: "MYELOPROLIFERATIVE DISEASES By DR. FATIMA AL-QAHTANI CONSULTANT HAEMATOLOGIST."— Presentation transcript:

1 MYELOPROLIFERATIVE DISEASES By DR. FATIMA AL-QAHTANI CONSULTANT HAEMATOLOGIST

2 WHO Classification Chronic Myeloproliferative Disease Chronic Myelogenous Leukaemia [Ph chromosome, t(9;22)(q34;q11), BCR/ABL- positive ] Chronic Neutrophilic Leukaemia Chronic Eosinophilic Leukaemia (and the hypereosinophilic syndrome) Polycythaemia Vera Chronic Idiopathic Myelofibrosis (with extramedullary haematopoiesis) Essential Thrombocythaemia Chronic Myeloproliferative Disease, Unclassifiable

3 WHO Classification Myelodysplastic / Myeloproliferative Diseases Chronic Myelomonocytic Leukaemia Atypical Chronic Myeloid Leukaemia Juvenile Myelomonocytic Leukaemia Myelodysplastic/Myeloproliferative Disease, Unclassifiable

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5 Myeloid Disorders Usual Features at Diagnosis Disease BM cellularity % Marrow Blasts Maturation Morphology Haemato- poiesis Blood count (s) Organo- megaly Myeloproliferatie disorder Usually increased Normal or slightly increased (<10%) PresentRelatively normal EffectiveOne or more myeloid cell lines increased Common Myelodysplastic syndromes Usually increased, occasionally decreased Normal or increased (<20%) PresentDysplasia of one or more myeloid lineage IneffectiveCytopenia (S)Uncommon Myelodysplastic/ myeloproliferative disease Usually increased Normal or increased (<20%) PresentDysplasia of one or more myeloid lineages frequent Effective or ineffective; may vary among involved lineages VariableCommon Acute myeloid leukaemia Usually increased, occasionally decreased Increased (≥ 20%) Varies, frequently minimal May or may not be associated with dysplasia in one or more myeloid lines Ineffective or effective Variableuncommon

6 Myeloproliferative Disease Recurring Genetic Abnormalities and Their Frequency (%) at diagnosis DiseaseSpecific abnormalities(%)Recurring, nonspecific cytogenetic/genetic abnormalities (%) CML, CPt(9;22)(q34;q11), BCR/ABL100 CML, AP/BP t(9;22)(q34;q11), BCR/ABL100+8, +9Ph,+19,i(17q), t(3;21)(q26;q22)(EVI1/AML1)80 CNLNone+8, +9, del(20q), del(11q14)~10 CELNone+8, t(5;12)(q33;p13)(TEL/PDGFβR), dic(1;7), 8p11 (FGFR1) ? PVNone +8, +9, del(20q), del(13q), del(1p11)~15 CIMFNone+8, del(20q), -7/del(7q), del(11q), del(13q)~35 ETNone+8, del (13q)~5 CML, CP = Chronic myelogenous leukaemia, chronic phase; CML, AP/BP= Chronic myelogenous leukaemia, accelerated or blast phase; CNL = Chronic neutrophilic leukaemia; CEL = Chronic eosinophilic leukaemia; PV = Polycythaemia Vera; EVI-1 = ecotropic viral integration site 1 CIMF = Chronic idiopathic myelofibrosis; ET = Essential thrombocythaemia ? = Insufficient data available

7 Chronic Idiopathic Myelofibrosis Prefibrotic Stage Clinical findingsMorphological findings Spleen and liver: No or mild splenomegaly or hepatomegaly Blood: No or mild leukoerythroblastosis No or minimal red blood cell poikilocytosis; few if any dacrocytes Splenomegaly: Haematologic parameters variable, but often: Mild anaemia Mild to moderate leukocytosis Mild to marked thrombocytosis Bone marrow: Hypercellularity Neutrophilic proliferation Megakaryocytic proliferation and atypia (Clustering of megakaryocytes, abnormally lobulated megakaryocytic nuclei, naked megakaryocytic nuclei) Minimal or absent reticulin fibrosis

8 Chronic Idiopathic Myelofibrosis Fibrotic Stage Clinical findingsMorphological findings Spleen and liver: Moderate to marked splenomegaly and hepatomegaly Blood: Leukoerythroblastosis Prominent red blood cell poikilocytosis with dacrocytes Haematology: Moderate to marked anaemia Low, normal or elevated WBC Platelet count decreased, normal or elevated Bone Marrow: Reticulin and/or collagen fibrosis Decreased cellularity Dilated marrow sinuses with intraluminal haematopoiesis Prominent megakaryocytic proliferation and atypia (clustering of megakaryocytes, abnormally lobulated megakaryocytic nuclei, naked nuclei) New bone formation (osteosclerosis)

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13 Essential Thrombocythaemia Diagnostic Criteria Positive Criteria 1.Sustained platelet count ≥600X10 9 /L 2.Bone marrow biopsy specimen showing proliferation mainly of the megakaryocytic lineage with increased numbers of enlarged, mature megakaryocytes Criteria of exclusion 1.No evidence of polycythaemia vera (PV) - Normal red cell mass or Hb <18.5g/dl in men, 16.5g/dl in women - Stainable iron in marrow, normal serum ferritin or normal MCV - If the former condition is not met, failure of iron trial to increase red cell mass or Hgb levels to the PV range 2.No evidence of CML - No Philadelphia chromosome and no BCR/ABL fusion gene

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16 Essential Thrombocythaemia Diagnostic criteria (Continued) 3.No evidence of chronic idiopathic myelofibrosis - Collagen fibrosis absent - Reticulin fibrosis minimal or absent 4.No evidence of myelodysplastic syndrome - No del(5q), t(3;3)q21;q26), inv(3)(q21q26) - No significant granulocytic dysplasia, few if any micromegakaryocytes 5.No evidence that thrombocytosis is reactive due to: - Underlying inflammation or infection -Underlying neoplasm -Prior splenectomy

17 Giant Plat

18 Megakaryocytes in Clusters

19 Polycythaemia Vera Hb: >17.5 gm/dl > 15.5 gm/dl -RBC: > 6.0 X /L > 5.5X10 12 /L -PCV: > 51% > 48% -TRCV : > 36 ml/kg (25-35) > 32 ml/kg (22-32) -TPV: 40 – 50 ml/kg

20 Classification of Erythrocytosis Raised PCV (female >0.48; male>0.51) RCM (Interpreted using ICSH reference values) Increased RCMNormal RCM Absolute erythrocytosisApparent erythrocytosis Abbreviations: PCV = Packed Cell Volume; RCM = red cell mass; ICSH = International Council for Standardization in Haematology;

21 Primary Erythrocytosis Congenital # Truncation of the EPO receptor* Acquired Polycythaemia Vera* Secondary Erythrocytosis Congenital # e.g., high oxygen affinity Hb, autonomous high EPO production Acquired e.g., hypoxemia, renal disease # Sometimes familial * The only condition to be defined in this category at present EPO = erythropoietin

22 Polycythaemia Vera Causes Primary : Polycythaemia Vera Secondary: 1.Erythropoietin compensatory increase: High Altitude C.V. disease Pulmonary disease High Affinity Hb Heavy smoking Methaemoglobinaemia 2.Abnormal erythropoietin production: Renal diseases. Massive uterine fibromatosis Hepatocellular Carcinoma Cerebellar Haemangioblastoma Relative: Stress, Dehydration, Plasma Loss.

23 Polycythaemia Vera Clinical Features Headache, Lethargy, Dyspnea Weight Loss, Night Sweats Generalized pruritis (Increase after hot bath) Plethoric Appearance Haemorrhage & Thrombosis Hypertension (In about 1/3rd of the patients) Gout (Increased Uric Acid) Peptic Ulcers (In 5 – 10% of the patients) Splenomegaly (In 2/3rd of patients) Accidental Discovery (On Routine exam)

24 Polycythaemia Vera Laboratory Investigations C.B.C -Neutrophil Alkaline Phosphatase (N.A.P.) -Serum B 12 & B 12 binding capacity -Bone Marrow - Blood Viscosity -Uric Acid Level - Hb Electrophoresis -Arterial Oxygen Tension - T.R.C.V. -I.V. Pyelography, CT & US - JAK2: 74 – 97 % (PV) -Erythropoietin Assay 33 – 57 % (ET) 35 – 50 % (MF)

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30 Polycythaemia Vera Proposed diagnostic criteria A1 Raised red cell mass B1 Thrombocytosis (>25% above mean normal Platelet count>400X10 9 /1 predicted value) A2 Absence of a cause of B2 Neutrophil leukocytosis Secondary Polycythaemia neutrophil count >10X10 9 /1 A3 Palpable splenomegaly B3 Splenomegaly demonstrated by isotope/ultrasound scanning A4 Clonality marker B4 Characteristic BFU-E growth e.g., abnormal marrow karyotype or reduced serum erythropoietin A1 + A2 + A3 or A4 establishes PV A1 + A2 + Two of B establishes PV

31 Polycythaemia Vera Classic Polycythaemia Vera Study Group Diagnostic Criteria A1 ↑ Red Cell Mass B1 Thrombocytosis Male ≥36 ml/kg Platelet count >400,000/µl Female ≥32ml/kg B2 Leukocytosis >12,000/µl (No fever or infection) A2 Normal Arterial B3 ↑ Leukocyte Alkaline O 2 Saturation ≥92% Phosphatase score >100 (No fever or infection) A3 Splenomegaly ↑ Serum B 12 (>900pg/ml) or ↑ Unbound B 12 binding capacity (>2200pg/ml) Diagnosis is acceptable if the following combinations are present: A1 + A2 + A3 or A1 + A2 + any two from Category B.

32 Polycythaemia Vera Treatment Venesecton Radioactive Phosphorus (P 32 ) Chemotherapy: e.g. Hydroxyurea


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