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DISORDERS
Hawwa Najiza
Rithika Sriram
Saloni Sawarthia
Introduction
Neoplastic
Proliferation
of white cells
Histiocytic or
Myeloid Lymphoid
Dendritic cell
Neoplasms Neoplasms
neoplasm
MYELOID
NEOPLASM
• Myeloproliferative disorders - clonal haematopoietic stem cell disorders
elements
WHO Classification of MPNs:
o Chronic myeloid leukemia, bcr-abl positive
o Chronic neutrophilic leukemia
o Chronic eosinophilic leukemia, not otherwise specified
o Polycythemia vera
o Primary myelofibrosis
o Essential thrombocytosis
o Mastocytosis
o Myeloproliferative neoplasms, unclassified
o Myelodysplastic syndromes
Chronic Myeloid Leukemia
• Commonest leukemia
• 30-80 years of age, Males
Constitutive
(+) of tyrosine
kinase
BCR-ABL
Oncoproteins Increased cell
(p210) proliferation
Inhibition of
apoptosis
Natural History
• Chronic / Stable / Indolent phase (3-5 years) : Blast cells <10%
• Blast phase/ crisis : Blast cells >20% (AML or ALL) Cause of death
Clinical Features
Symptoms :
• Fever, weight loss,anorexia, sweating and heat intolerance -Hypermetabolic state
• Peripheral smear :
1. Normocytic Normochromic anemia,
2. WBCs: >20,000/µL.
3. Shift to left – predominant cells - neutrophils and myelocytes.
4. Basophils , eosinophils present.
5. Blasts <10%. NAP/LAP score decreased
6. Platelet : increased
• Bone Marrow
1. Hypercellular. M:E ratio- 20:1
2. Myelopoiesis. Blasts <10%
3. Dwarf megakaryocytes
4. Sea Blue histiocytes
5. Fibrosis , reticulum stain
• FISH
• Biochemical :
1. Uric acid increased
2. LDH, ALP Vit B12 increased
• Accelerated Phase :
PS and Bone Marrow :
1. Increasing anemia
2. Blasts : 10-19%
3. Striking basophila (20%)
4. Thrombocytopenia
• Blast Phase :
1. Blasts >20%
2. Basophils >20%
3. Thrombocytopenia
4. Bone marrow fibrosis
Goal of treatment
ADP P
P P P
ATP
P P P
SIGNALING
Imatinib Mesylate:
MOA
• Degree of matching
• Preparative regimen
Allogenic Stem Cell Transplantation:
Preparative regimens
• Cyclophosphamide plus total-body irradiation
• Massive splenomegaly
• Granulocytic sarcoma
• ↑TLC
• ↑ Eosinophilic count
• Diagnosis requires presence of both major criteria and 1 minor or first major and 2
minor criteria
MANAGEMENT
• Aspirin: Reduces risk of thrombosis
• Venesection: Prompt relief of hyperviscosity symptoms (repeated
every 5-7 days until hematocrit is reduced to below 45%)
• Hydroxycarbamide or interferon-alfa: Reduces risk of vascular
occlusion, controls spleen size and reduces transformation to
myelofibrosis
• Radioactive phosphorus: Reserved for older patients
PROGNOSIS
• Median survival after diagnosis in treated patients: >10years
• Complications:
Increased risk of arterial thrombosis, particularly stroke and venous
thromboembolism
May convert to another myeloproliferative disorder or acute leukaemia
or myelofibrosis
MYELOFIBROSIS
ETIOLOGY
Marrow: Hypercellular (excess of abnormal megakaryocytes)
Fibrosis of marrow
• Age group: >50 years
• Signs and symptoms:
Lassitude
Weight loss
Night sweats
Massive splenomegaly due to extramedullary hematopoiesis
BLOOD PICTURE
• Leukoerythroblastic anemia with circulating immature RBCs
(increased reticulocytes and nucleated RBCS) and granulated
precursors (myelocytes)
• RBCs shaped like teardrops (teardrop poikilocytes)
• Giant platelets
DIAGNOSIS
• Biopsy shows excess of megakaryocytes, increased reticulin and fibrous
tissue replacement
• Presence of a JAK-2 mutation supports the diagnosis
• WBC counts: low to moderately high
• Platelet count: high, normal, or low
• Urate levels: may be high due to increased breakdown
• Folate deficiency
MANAGEMENT
• Red cell transfusions for anemia
• Folic acid to prevent deficiency
• Hydroxycarbamide: To control spleen size, WBC count or systemic
symptoms
• Splenectomy for a grossly enlarged spleen
• Ruxolitinib: Inhibitor of JAK-2 recently being used
ESSENTIAL THROMBOCYTOSIS
• Increased proliferation of megakaryocytes Raised level of circulating
platelets that are dysfunctional
• Age group: 60 years
• Presents with vascular occlusion or bleeding or with an asymptomatic
isolated raised platelet count
• May progress to myelofibrosis or acute luekaemia
SYMPTOMS
• Asymptomatic
• Digital ischemia from microvascular thrombi
• Pruritis
• Erythromelalgia
• Hemorrhage
DIAGNOSIS
• Important to rule out other reactive causes of thrombocytosis
• High platelet count
• May have splenomegaly
• Presence of JAK-2 mutation supports the diagnosis
MANAGEMENT
• Low dose aspirin
• Oral hydroxycarbamide
• Anagrelide, an inhibitor of megakaryocyte maturation: For those with
platelet count >1000*109/L, and risk factors for thrombosis like
hypertension or diabetes
• Intravenous radioactive phosphorus useful in old age
MYELODYSPLASTIC SYNDROMES
• Heterogenous group of acquired clonal stem cell disorders
• Progressive cytopenias, dysplasia in one or more cell lines, ineffective
hematopoiesis
• Risk of development of AML
• Can be primary or secondary
• Produce several structural abnormalities during maturation and
premature cell destruction
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