Myeloproliferative diseases by dr kamal e higgy consultant haematologist
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MYELOPROLIFERATIVE DISEASES By DR. KAMAL E. HIGGY CONSULTANT HAEMATOLOGIST. Myeloid Disorders Usual Features at Diagnosis. WHO Classification Chronic Myeloproliferative Disease

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Myeloproliferative diseases by dr kamal e higgy consultant haematologist


Myeloid disorders usual features at diagnosis
Myeloid DisordersUsual Features at Diagnosis

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

WHO Classification

Myelodysplastic / Myeloproliferative Diseases


  • Chronic Myelomonocytic Leukaemia

  • Atypical Chronic Myeloid Leukaemia

  • Juvenile Myelomonocytic Leukaemia

  • Myelodysplastic/Myeloproliferative Disease, Unclassifiable

Myeloproliferative disease recurring genetic abnormalities and their frequency at diagnosis
Myeloproliferative DiseaseRecurring Genetic Abnormalities and Their Frequency (%)at diagnosis

Polycythaemia Vera


  • Hb : Males >17.5 gm/dl

    Females > 15.5 gm/dl

  • RBC : Males > 6.0 X 1012/L

    Females > 5.5X1012/L

  • PCV : Males > 51%

    Females > 48%

  • TRCV : Males > 36 ml/kg (25-35)

    Females > 32 ml/kg (22-32)

  • TPV : 40 – 50 ml/kg

Classification of Erythrocytosis

Raised PCV (female >0.48; male>0.51)


(Interpreted using ICSH reference values)

Increased RCMNormal RCM

Absolute erythrocytosis Apparent erythrocytosis

Abbreviations: PCV = Packed Cell Volume; RCM = red cell mass;

ICSH = International Council for Standardization in Haematology;

Primary Erythrocytosis

Congenital #

Truncation of the EPO receptor*


Polycythaemia Vera*

Secondary Erythrocytosis

Congenital #

e.g., high oxygen affinity Hb,

autonomous high EPO production


e.g., hypoxemia, renal disease

# Sometimes familial

* The only condition to be defined in this category at present

EPO = erythropoietin

Polycythaemia Vera



  • Primary : Polycythaemia Vera

  • Secondary:

    1. Erythropoietin Compensatory Increase:

    High Altitude

    C.V. disease

    Pulmonary disease

    High Affinity Hb

    Heavy smoking


    2. Abnormal Erythropoietin Production:

    Renal diseases.

    Massive uterine fibromatosis

    Hepatocellular Carcinoma

    Cerebellar Haemangioblastoma

  • Relative: Stress, Dehydration, Plasma Loss.

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)

Polycythaemia Vera

Laboratory Investigations


  • C.B.C

  • Neutrophil Alkaline Phosphatase (N.A.P.)

  • Serum B12 & B12 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)

Polycythaemia Vera

Classic Polycythaemia Vera Study Group

Diagnostic Criteria


A1 ↑ Red Cell MassB1Thrombocytosis

Male ≥36 ml/kg Platelet count >400,000/µl

Female ≥32ml/kgB2Leukocytosis >12,000/µl

(No fever or infection)

A2Normal ArterialB3↑ Leukocyte Alkaline

O2 Saturation ≥92%Phosphatase score >100

(No fever or infection)

A3Splenomegaly ↑ Serum B12 (>900pg/ml)


↑ Unbound B12 binding

capacity (>2200pg/ml)


  • Diagnosis is acceptable if the following combinations are present: A1 + A2 + A3 or A1 + A2 + any two from Category B.

Polycythaemia Vera

Proposed diagnostic criteria


A1 Raised red cell mass B1 Thrombocytosis

(>25% above mean normal Platelet count>400X109/1

predicted value)

A2 Absence of a cause of B2 Neutrophil leukocytosis

Secondary Polycythaemianeutrophil count >10X109/1

A3 Palpable splenomegalyB3 Splenomegaly demonstrated

by isotope/ultrasound scanning

A4 Clonality marker B4 Characteristic BFU-E growth

e.g. - abnormal marrow karyotypeor reduced serum erythropoietin

- JAK2


A1 + A2 + A3 or A4 establishes PV

A1 + A2 + Two of B establishes PV

Polycythaemia Vera



  • Venesecton

  • Radioactive Phosphorus (P32)

  • Chemotherapy:

    e.g. Hydroxyurea

Essential thrombocythaemia diagnostic criteria
Essential ThrombocythaemiaDiagnostic Criteria

Positive Criteria

  • Sustained platelet count ≥600X109/L

  • Bone marrow biopsy specimen showing proliferation mainly of the megakaryocytic lineage with increased numbers of enlarged, mature megakaryocytes

    Criteria of exclusion

  • 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

  • No evidence of CML

    - No Philadelphia chromosome and no BCR/ABL fusion gene

Essential thrombocythaemia diagnostic criteria continued
Essential ThrombocythaemiaDiagnostic criteria(Continued)

  • 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


  • No evidence that thrombocytosis is reactive due to:

    - Underlying inflammation or infection

    -Underlying neoplasm

    - Prior splenectomy


in Clusters

Chronic Myelogenous Leukaemia

Presenting Manifestations




Less Common

Symptoms due to the raised metabolic rate

Haemorrhagic Manifestations, especially bruising

Chronic Myelogenous Leukaemia

Presenting Manifestations (Cont…)


  • Acute abdominal pain

  • Bone or joint pains

  • Menstrual disturbances

  • Neurological symptoms

  • Priapism

  • Gout

  • Skin disorder

  • Disturbances of vision or hearing

  • Accidental discovery on routine blood examination

Chronic Myelogenous Leukaemia

Evolution of the disease

Chronic Phase

Accelerated Phase

Blastic Transformation


Chronic Myelogenous Leukaemia

Laboratory Investigations

  • CBC

Chronic Myelogenous Leukaemia

Laboratory Investigations (Cont…)

  • Neutrophil Alkaline Phosphatase

  • Bone Marrow Examination.

  • Serum B12 & B12 binding capacity

  • Cytogenetic Studies

    (Ph1) chromosome [ t ( 9 : 22 ) ]

  • DNA restriction enzyme analysis

    BCR-ABL (Breakpoint Cluster Region)

Chronic myelogenous leukaemia accelerated phase
Chronic Myelogenous LeukaemiaAccelerated Phase

  • Blasts 10% to 19% of peripheral blood white cells or bone marrow cells

  • Peripheral blood basophils at least 20%

  • Persistent thrombocytopenia (<100X109/L) unrelated to therapy or persistent thrombocytosis (> 1000X109L) unresponsive to therapy

  • Increasing spleen size and increase WBC count unresponsive to therapy

Chronic myelogenous leukaemia accelerated phase cont
Chronic Myelogenous LeukaemiaAccelerated Phase (Cont…)

  • Cytogenetic evidence of clonal evolution (i.e., the appearance of an additional genetic abnormality that was not present in the initial specimen at the time of diagnosis of chronic phase CML)

  • Megakaryocytic proliferation in sizable sheets and clusters, associated with marked reticulin or collagen fibrosis, and/or severe granulocytic dysplasia, should be considered as suggestive of CML-AP

    These findings have not yet been analyzed in large clinical studies, however, so it is not clear if they are independent criteria for accelerated phase. They often occur simultaneously with one or more of the other features listed

Chronic myelogenous leukaemia blastic phase bp
Chronic Myelogenous LeukaemiaBlastic Phase (BP)

Diagnosis is established if one or more of following is present:

  • Blasts 20% or more of peripheral blood white cells or bone marrow cells

  • Extramedullary blast proliferation

  • Large foci or clusters of blasts in bone marrow biopsy

Chronic myelogenous leukaemia chronic phase bp treatment
Chronic Myelogenous LeukaemiaChronic Phase (BP) Treatment

  • Hydroxyurea (HU):

    WBC/ulHU (mg/kg BW/DAY)

    >50,000 50

    15-50,000 30 – 40

    <15,000 25

  • Busulphan

  • Alpha – Interferon:

    5 MU/DAY

    7.5 MU/DAY if WBC > 10,000/mcl

    10 MU/DAY if WBC > 20,000/mcl

    3 MU/DAY if cytopenia develops


  • Gleevec