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Chronic Myeloproliferative Neoplasms - Coggle Diagram
Chronic Myeloproliferative Neoplasms
Classifications
Chronic Myelogeneous Leukaemia (CML)
Classical Myeloproliferative neoplasms
Polycythaemia Vera (PV)
Essential thrombocytosis (ET)
Primary myelofibrosis (PMF)
Rare
Chronic Eoisinophilic Leukaemia (CEL)
Chronic neutrophilic leukaemia (CNL)
Myeloproliferative neoplasm not otherwise specified (NOS)
Defining MPNs
Originally morpholigical assessment
Disease defining molecular abnormalities (CML)
3.Disease asssociated molecular abnormalities (PV/ET/MF)
Genetic abnormalities
Translocations / point mutations
Chronic Myeloid Leukemia (CML)
Genetics
Philadephia chromosome
t(9;22) translocation
brc-alb Gene
Fusion protein tyrosine kinase
Epidemiology
Median age 45-55
Incidence increases with age
Male predominance
Causes
Ionising radiation
Atomic bomb survivors
Women with uterine cervical carcinoma treatment
Ankylosisng spondylitis pts treatment
Presentations
Aysmptomatic picked up on Blood test (↑WBC)
Symptoms of anaemia
Anorexia and weight loss
Splenolmegaly
Clinical Phases
Chronic phase
Advanced phases
Accelerated phase
Blastic phase - blast crisis
Treatment
Tyrosine kinase inhibitors
MOA
No 2nd messanger
Cell death
Blocks active site of tyrosine kinase
DAsatinib
Nilotinib
Bosutinib
Ponatinib
Imatinib
Allogeneic bone marrow transplant
Myeloproliferative Neoplasms (MPN)
Types
Polycythemia Vera
Essential thrombocytosis
Primary Myelofibrosis
Genetics
Philadelphia chromosome negative
Aquired cloncal stem cell disorders
Molecular / cytogeneic abnormalites
Driver Mutations
Mutations in haematopoietic stem cells that result in increased mature myeloid cells
JAK2 gene
Enhanced signalling in abscence of Erythropoeitin
MPL gene
CaLR gene
Definition
A collection of haematological malignancies characterised by the overproduction of one or more types of blood cells, occurin gin the abscence of an identifiable stimulus
Presentation / Clinical features
Increased risk of thrombosis and bleed
Propensity to transform to acute leukemia
Bone marrow fibrosis
Extramedullary haematopoiesis (big spleen)
Polycythaemia
Types
Absoloute Polycythemia
Primary Polycythemia Vera
JAK2 positive
Secondary Polycythemia
Tissue hypoxia causing ↑EPO production
Lung disease
CV disease
High altitude
Haemoglobin variants
Inapproapriate EPO production
Renal tumour producing EPO
Relative Polycythemia
Polycythemia Vera
Epidemiology
Older pts
M=F
Presentation
Gradual onset symptoms
Headaches, dizziness
Generalised
pruritus
especially after bath
Bleeding episodes
Plethoric appearance
Splenomegaly
Gout
Thrombotic episodes
WHO critera for diagnosis
Major Criteria
Bone marrow biobsy showing hypercellularity
JAK2 mutation V617F or JAK2 exon 12 mutation
Haemoglobin > 16.5 g/dL in men or 16 g/dL in women
HCT > 49% m or 48% w
More than 25 % increased in red cell volume
Minor Criteria
Subnormal EPO level
Dx
All 3 major
First 2 major + 1 minor
Treatment
Aggressive Phlebotomy
Aspirin 75mg daily
Reduction in MI and Stroke
Essential Thrombocytosis
Causes of ↑Platelets
Reactive
Haemorrhage
Trauma
Chronic Iron deficiency
Malignancy
Chronic infections
Post-operative
Connective tissue disease
Endogenous
Essential thrombocytosis
Chronic myeloid leukemia
Polycythemia vera
Myelofibrosis
WHO Criteria for Dx
Major Criteria
sustained thrombocytosis with platelets >450x10^9 / L
Presence of clonal marker sucha s
JAK2 V617F
CALR
MPL
No evidence of alternative myeloid malignancy
Bone marrow biopsy showing proliferation of mainly megakaryocyte lineage
No significatn increase in granulopoiese
Less than grade 1 bone marrow fibrosis
Minor Criteria
Presence of a clonal marker
No evidence of a reactive process
Dx
All 4 major
First 3 major + all minor criteria
Risk of Thrombosis
High
Age >60
Hx of previous thrombosis
Pl count >1500
Tx
Lower platelet count
Aspiring
Low
Age <40
No hx of thrombosis
Tx
Aspirin alone
Myelofibrosis
Epidemiology
Rarest of classic myeloproliferative disorders
Older pt with hx of ET / PV
Male predominance
Presentation / Clincal Features
Pain 2* to massive hepatosplenomegaly
Anaemia
Hypermetabolic symptoms
Night sweats
Pruritus
Weight loss
Fatigue
High symptom burden
Pathogenesis
Progressive generalised fibrosis of bone marrow - reactive process
Development of haematopoiesis in spleen / liver - extramedullary
Normal fibroblast respond to abnormal cytokines released by megakaryocytes
Cytokines - TGF-β , PDGF, FGF
Labratory Investigation
Leucoerythroblastic blood picture
Treat poikilocytes
Prognostic Factors
Hb
Constitutional symptoms
WBC
PB blasts
Age
Treatment
JAK2 inhibitors
Ruxolitinib
Allogeneic transplant
Blood transfusion for anaemia
SUpportitive
Goals of Treatments
Cure
Prevent thrombosis / bleeding
Prevent transformation
Ameliorate symptoms
Ameliorate symptoms
Improve blood counts
Cytogenetic / molecular responses
