Post on 03-Apr-2018
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Rachmat SumantriSub Division of Hematology Medical Oncology
Department of Internal Medicine
Padjadjaran University
Hasan Sadikin Hospital
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MPDs divided into two groups : ACUTE and CHRONIC
ACUTE : Acute non lymphocytic leukemia (ANLL)
CHRONIC : Chronic myelocytic leukemia
Polycythemia vera
Idiopathic myelofibrosis
Essential thrombosis
Characterized by a hyper cellularbone marrow with increasedquantities of one or more cellular
lineages in the peripheral blood
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The Clinical Variants of The CMPDs
may share, to varying extents :
1. Affects middle aged and older groups
2. Asymptomatic onset
3. Panhyperplasia of bone marrow
4. Extra medullary hematopoesis5. Fibroblast proliferation and reticulin / collagen formation in
bone marrow
6. Frequent transitions between these disorders, withoverlapping manifestation
7. Terminating in acute leukemia
8. Elevation of platelet count ; Giant or bizzare platelets, or both
9. Hemorrhagic and thrombotic complications
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OTHERS :
1. CYTOGENETIC ABNORMALITIES
2. ABNORMAL P53
genesApoptosis induced by the P53 ,
in the presence of altered or absent p53
apoptosis does not occur, resulting in
continued proliferation.
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RELATIONSHIP BETWEEN
THE VARIOUS MPDS
IMFET
PV
AML
CML
ALL
1 2%
10 15%
15 20%
60 70%25% 5%1 2%
2 5%
1 2%
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CHRONIC MPD
1. Polycythemia Vera
2. Chronic Myelogenous Leukemia3. Idiopathic Myelofibrosis
4. Essential Thrombocytosis
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POLYCYTHEMIA VERA
PV is a hematopoietic stem cell disorder
predominantly characterized by
accelerated erythropoiesis, proliferation
of myeloid and megakaryocytic
elements of the bone marrow.
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ELEVATED HEMATOCRIT 50%
Absolute Erythrocytosis
(Increased RC Volume)
Relative Erythrocytosis
(Normal RC Volume)
POLYCYTHEMIA VERA
SECONDARY ERYTHROCYTOSISDEHYDRATION
STRESS POLYCYTEMIA
(Gaisbock syndr.)
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PATHOGENESIS
Abnormal Pluripotent Cell
Erythroid colonies grow independentlyfrom EPO
2 Cases per 100,000 population
Median age 60 years
EPI DEMIOLOGY
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CLINICAL PICTURES
Insidious onset
Symptoms related to increased red cell volume or hyperviscocity
Cerebral circulatory disturbances : headache, dizzy, vertigo,
visual phenomena
Hemorrhage
Thrombosis
Splenomegaly, modest hepatomegaly
Reddish purple color or the face, nose, ears, lips (PLETHORA)
Itching
Fever
Gout
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LABORATORY FEATURES
Elevation of RBC, HB, HT are the mostimportant findings
HT > 58% in men > 52% in women
Red cell mass 36 ml/mg in men
32 ml/kg in women
Elevation of WBC is moderate
(12 25. 109/L)
Thrombocytosis (450 1000 x 109 /L)
O2
saturation normal
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PV Sec Eryth Relative Eryth
Splenomegaly + 75%
Hepatomegaly + 35%
Heart or lung +
Dis
Cyanosis +
Red Cell Mass NormalWBC 80% Normal NormalPlatelet 50% normal NormalB12 75% Normal NormalO
2saturation Normal Normal
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PV STUDY GROUP CRITERIA
MAYOR CRITERIA1. Elevated Red Cell Mass
2. Normal Arterial O2 Saturation
3. Splenomegaly
MINOR CRITERIA
1. Leukocytosis
2. Thrombocytosis
3. Elevated Leukocyte Alkaline Phosphatase4. Increased serum Vit. B12
ALL from mayor
or elevated red cell mass + two minor criteria
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SECONDARY ERYTHROCYTOSIS
COPD
Cyanotic congenital heart disease
Cirrhosis
Pickwickian Syndrome
High Altitude
Smoking
RELATIVE ERYTHROCYTOSIS
Dehydration
GAISBOCKS Syndrome (Hypertensive,Obese, smoking)
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TREATMENT
PHLEBOTOMY
CHEMOTHERAPY : Hydroxyurea,
Busulphan, 32p
PROGNOSIS
Survival rate 8 15 years
Thrombohemorrhagic Events : 40% of deaths
10
15% : Malignant Transformation to AML
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ESSENTIAL
THROMBOCYTOSIS
1. CLONAL
- Essential (Primary) Thrombocytosis
- Polycythemia Vera
- Chronic Myelogenous Leukemia
- Myelofibrosis (Myeloid Metaplasia)2. FAMILIAL
Autosomal Dominant
MAYOR CAUSES OF THROMBOCYTOSIS
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Cont.
3. REACTIVE (SECONDARY) THROMBOCYTOSIS
A. Transient Reactive Processes- Acute Blood Loss
- Rebound
- Acute Infection, Inflammation
- Response to ExerciseB. Sustained Processes
- Iron Deficiency
- Post Splenectomy
- Malignancy- Chronic Inflammatory and Infection Diseases
- Hemolytic Anemia
- Response to Drug (Vincristine, Epinephrine,
ATRA, Growth Factors)
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PATHOGENESIS
Clonal : Multipotensial Hematopoietic
Cell
Chromosome Abnormality (17)
JAK2 Gene : A Tyrosine kinase forsignaling from cell membrane receptor
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Splenomegaly in 40%
Complications BLEEDING OR
THROMBOSIS
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DIAGNOSTIC CRITERIA
1. Platelet > 600.000/mm3
2. Normal Red Cell Mass
< 36 ml/kg
< 32 ml/kg3. Stainable iron in marrow or failure of iron trial4. No Philadelphia Chromosome
5. Collagen fibrosis of marrow :
Absent or < 1/3 biopsy area withoutsplenomegaly nor leukoerythroblastic reaction
6. No known cause for reactive thrombocytosis
7. Megakaryocytes in clumps
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CLINICAL RISK OF
THROMBOHEMORRHAGIC
THROMBOSIS BLEEDING
INCREASED
RISK Previous History
of Thrombosis Cardiovascular
Risk Factors
Especially Smoking
Age > 60
Inadequate Control
of Thrombocytosis
Aspirin or
NSAID
> 1.500.000
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CLINICAL FEATURES
CLONALTHROMBOCYTOSIS
REACTIVE
Splenomegaly
Platelet morphology
Platelet function
Thrombotic
complications
40%
Giant plateletOften abnormal
Digital, cerebral, large
vessel arterial or venous
thrombosis
NormalNormal
No
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THERAPY
CYTOREDUCTION
HYDROXYUREA
NON ALKYLATING MYELOSUPPRESIVEAGENT
ANAGRELIDE
RECOMBINANT - INTERFERON ANTIPLATELET
ASPIRIN
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PROGNOSIS
Terminates by converting to acuteleukemia, myelodysplasia or
myelofibrosis
Better overall prognosis than other
MPDs 5 years survival : 80%
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IDIOPATHIC MYELOFIBROSIS
History : First reported in 1879 by HeuckSynonyms : Agnogenic myeloid metaplasia
Myelosclerosis
OsteosclerosisChronic Erythroblastosis
Myelofibrosis with Myeloid Metaplasia (MMM)
CHARACTERIZED BY :
Fibrosis of the marrow
Extramedullary hematopoesis
Leukoerythroblastosis and teardrops
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INCIDENCE AND ETIOLOGY
Annual incidence is 0.6 per 100,000
Male to female ratio = 2 : 1Age distribution : 50 70
Etiology : Mayority is unknownExposure to radiation,toxins
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PATHOGENESIS
STEM - CELL DEFECT
Mutation of multipotensial stem-cell
Bone marrow fibrosis occur
secondary, non neoplastic process
MARROW FIBROSIS :
Platelet derived growth factor
fibroblast collagen production
myelofibrosis
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CLINICAL PICTURES
Insidious, symptoms free for many years
Splenomegaly, hepatomegaly
Anemia
10% bleeding secondary to thrombocytopenia or
thrombocytosis
Bone pain
Hypermetabolism
Gout
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LABORATORY FINDINGS
Leukoerythroblastic
Teardrop formation
50% WBC increased, 35% WBCnormal, 15% WBC below normal
Platelet : normal, elevated or decreased
Bone marrow aspiration : Dry Tap Histologic : Reticulin, Fibroblast and
collagen increased
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DIFFERENTIAL DIAGNOSIS
Must be distinguished from other disease of theCMPDs, as well as differentiated from fibrosissecondary to infiltratif disorders
CML considered most frequently 15 20% patients PV undergo a transition to terminal
myelofibrosis with marked anemia, bone marrow
fibrosis and splenomegaly Secondary myelofibrosis : Metastatic carcinoma,
leukemia, granulomatous disorders (TBC,Histoplasmosis, Sarcoidosis)
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TREATMENT
TO IMPROVE QUALITY OFLIFE
PALLIATIVE
TRANSFUSION
STEROID ANDROGEN
SPLENECTOMY
ALLOPURINOL
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PROGNOSIS
Median survival 5 years Cause of death : Hemorrhage,
infection
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CASE STUDY
60 Y O MAN ADMITTED WITH PAIN ANDSWELLING OF LEFT LIMB,2 DAYS EARLIER HE
CAME TO EMG WITH HEADACHE,BLURRED
VISION,TINNITUS AND PRURITUS ESPECIALLYAFTER BATHING. He had been treated for gout for the
past 2 months
Physical examination : flushed face,engorged retinal
veins,ecchymosis on the legs,splenomegaly,nohepatomegaly
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Lab : Hb 18.8 gr% WBC 20.300
RBC 7.53x10/L
Platelet 870.000 Hct 58% O2 saturation 94%
Bone marrow:panhyperplasia and large
megakaryocyte,reticulin content slightly
increased
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comment
History and physical findings : presumptive
diagnosis of PV
Headache and blurred vision: hyperviscosityAs well as thrombotic episode. Plethora , engorged
retinal veins : blood vessels congestion
Generalized pruritus occurs in 30%
Phlebotomy and cytoreduction therapy must be
initiated
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