Neoplasm:

Myeloproliferative
Disorders
Myelodysplastic
Syndromes

Marvi G. Dulnuan, MD. FPSP

CHRONIC MYELOPROLIFERATIVE
DISEASES/ DISORDERS
Clonal proliferations of pluripotent stem cell
diseases

With expansion, excessive production and

accumulation of erythrocytes, granulocytes
and platelets.

Expansion occurs in varying combinations in

the bone marrow, peripheral blood and
tissues.
MPDs Classification:
FAB WHO
Chronic myelogenous Chronic myelogenous
leukemia leukemia
Polycythemia vera Polycythemia vera
Essential Essential
thrombocythemia thrombocythemia
Agnogenic myeloid Chronic idiopathic
metaplasia/myelofibrosis myelofibrosis
Chronic neutrophilic
leukemia
MPDs Clinical Signs and
symptoms
Generally present as stable chronic disorders

May transform:

CHRONIC SUBACUTE
ACUTE
DISEASE PHASE
LEUKEMIA
History
Easy fatigability
Anorexia, weight loss
Abdominal discomfort and early satiety secondary
to splenomegaly
Easy bruising, bleeding, and/or symptoms of
thrombosis
Swollen, painful joint(s) secondary to gouty arthritis
Priapism, tinnitus, or stupor
Left upper quadrant and left shoulder pain
Commonly, abnormal blood counts are noted on a
blood test performed for other reasons.
Physical Examination
Pallor, except in patients with
polycythemia vera

Plethora

Petechiae and/or ecchymosis

Palpable spleen and/or liver

Occasionally, syndrome of fever

accompanied by painful maculopapular
violaceous lesions on trunk, arms, legs,
Etiology
Precise cause is unknown.

Believed to be likely a multistep process

involving more than one gene.

An attribute common to these disorders

appears to be an acquired activating mutation
in the gene coding for various tyrosine kinases.

- Enhanced activity Clonal stem cell proliferation

CHRONIC
MYELOGENOUS/
MYELOBLASTIC
LEUKEMIA
CHRONIC MYELOGENOUS
LEUKEMIA
Incidence:

20% of all cases of leukemia.

Young and middle-aged adults (46-53)

markedly after 50 years of age.

Males > females.

Mortality rate = 1.5 per 100,000/ year.

Chronic Myeloid Leukemia (CML)
Cytogenetic abnormalities:
Abnormally small chromosome due to this translocation -
PHILADELPHIA CHROMOSOME

EGFR-TK
Over
expression

Tumor Growth
&
Malignant
Transformation
Chronic Myelogenous Leukemia (CML)
Symptoms associated with insidious clinical
onset, and may be discovered accidentally on
routine blood test.

Patients survive 1 year after onset, if without

remission

Have lower proliferative rates

Greater proportion of mature cells

Splenomegaly is often present and a prominent

Chronic Myelogenous Leukemia (CML)
Laboratory Features:
Blood:
Leukocyte count > 50 x 109/L (up to 300 x 109/L
)
Complete spectrum of granulocytic cells < 10
% blasts
Eosinophilia and basophilia
Anemia
Thrombocytosis; thrombocytopenia in 15%
Chronic Myeloid Leukemia (CML)

Laboratory Features:
Bone Marrow
Markedly hypercellular, with
granulocytic proliferation,
with all stages present
Eosinophil and basophil
porecursors are usually
increased
Erythroid precursors are
usually decrease
Chronic Myeloid Leukemia (CML)

Laboratory Features:

Decreased Leukocyte alkaline phosphatase

(LAP/NAP) score or absent (90%)
Chronic Myeloid Leukemia (CML)

Laboratory Features:

Other findings:
- Increased serum cobalamin and
transcobalamin
- Increased serum muramidase
CML: Clinical Course
1. Accelerated or aggressive phase

frequency and type of clinical symptoms, adverse changes

in laboratory values and poorer response to therapy than in
the chronic phase.

Characterized by progressive myeloproliferation

Blood or marrow blast count increases to 10 19%
Increasing leukocytosis
Peripheral basophilia > 20%
Persistent thrombocytopenia unrelated to therapy < 100 x
109/L
Trombocytosis > 1000 x 10 9/L
CML: Accelerated/ Aggressive Phase

Clonal Enhanced Increase

Evolution dyshematopoietic
morphologic
cell maturation patterns &
Functional

abnormalities
CML Course
2. Blast Phase
Progression to acute leukemia

Diagnostic criteria:
> 20% blast in the blood and bone marrow
Large aggregates of blasts in marrow and
other extramedullary locations
Blast lineage is myeloid in 70% of cases
and may include any myeloid cell types.
CML Blast Phase

Blast transformation appears because of

secondary genetic changes involving p53,
retinoblastoma (Rb) and other genes.
CML Treatment
Reduce tumor burden: Alkalyting agents

Improved survival:
Hydroxyureas and mercaptopurine to
inhibit uric acid build up
-Interferon stimulates a cell-mediated
anti-tumor response to reduce
cytogenetic remissions inhibits Ph +
clones(Tafiri).

Bone marrow and stem cell transplantation

has been reported curative I patients < 55
Differentiation of Leukemoid Reaction
and CML

Leukemoid CML
Reaction
Total WBC > 50 to 100 x 109/L > 50 to 300
Count with a shift to the left x109/L

Eosinophils/
Basophils Rare Increased

LAP/NAP
Score > 100 < 10

organomegal Absent Present

y
POLYCTHEMIA
VERA
Polycythemia Vera
A clonal MPD affecting primarily the
erythroid series

Characterized by panmyelosis - with

excessive erythropoiesis, granulopoiesis
and megakaryopoiesis
Polycythemia vera
Incidence:
Occurs in about 5/1,000,000 people

Men than women (about 1.4:1 male: female

ratio).

Begins in middle age,

with mean age at diagnosis is 60 yr
(range, 15 to 90 yr; rarely in childhood)
5% of patients are < 40 yr at onset.
Polycythemia vera
Pathophysiology

RBC production is autonomous with endogenous

of erythroid colonies growing in without
erythropoietin vitro erythropoietin.

Pathology maybe associated to:

decreased expression of the thrombopoietin
receptor, c-Mpl and
over expression of the polycythemia rubra vera-
1messenger.

Polycythemia vera : Signs and

Symptoms
Often asymptomatic.
Occasionally, due increased blood volume
and viscosity ischemic episodes
Hepatomegaly is common, and > 75% of
patients has splenomegaly (which may be
massive).
Thrombosis can occur in most vessels
strokes, MI
Bleeding (typically GI) occurs in 10 to 20% of
patients.
Complications of hyperuricemia (eg, gout, renal
calculi)
PV : Diagnosis
Diagnosis include:
1. increased RBC mass of 36 ml/Kg in males and 32
ml/Kg in females
2. Oxygen saturation at 92%
3. Splenomegaly

OR any 2 of the above plus any two of the

following:

4. Thrombocytosis > 400 x 109/L

5. Leukocytosis > 12x 109/L without fever or infection
6. Increase in leukocyte alkaline phosphatase (LAP)
7. Increase in Serum Vitamin B12 or unbound Vitamin B12
binding capacity
 WHO Criteria for Diagnosis
Criteria
A1 Elevated Red Cell Mass > 25% above mean normal
predicted value or
Hemoglobin > 18.5 g/dL in men; 16.5 g/dL in women
A2 No cause of secondary eryhtrocytosis, including:
Absence of familial erythrocytosis
No elevation due to:
- Hypoxia
- High oxygen affinity hemoglobin
- Truncated erythropoietin receptor
- Inappropriate erythropoietin production by any tumor
A3 Splenomegaly
A4 Clonal genetic abnormality (other than Ph chromosome or
BCR/ABL fusion gene) in bone marrow cells
A5 Endogenous erythroid colony formation in vitro
B1 Thrombocytosis > 400 x 109/L
B2 Leukocytosis with total WBC count > 12 x 109/L
B3 Bone marrow biopsy showing pnamyelosis with prominent
erythroid and megakaryocytic proliferation
Laboratory Diagnosis: PV
Laboratory Diagnosis: PV
Laboratory Diagnosis: PV
Laboratory Diagnosis PV
PV: Clinical Course
1. Patients live 10-20 years under good
control
Phlebotomy, chlorambucil, etc

2. 20 40 % of patient progress to spent or

post-polycythemia phase

3. Acute leukemia or myelodysplastic

syndrome
Slight increase by 2-3% in patients
treated with phlebotomy alone
Greater (10%) in patients treated with
Essential
Thrombocythemia
Essential Thrombocythemia

This is a clonal MPD

With increased megakayopoiesis and

sustained thrombocytosis

Essential Thrombocythemia
Incidence:
Generally appearing after age 60 (usually
between 50 70) with equal sex distribution

Second peak of by age 30 commonly in

women> men

No specific genetic abnormality

 Essential Thrombocythemia

Clinical Features

50% of patients are usually asymptomatic thrombocytosis.

Bleeding is usually mild and manifests as epistaxis, easy

bruisability, or GI bleeding.

Digital ischemia may occur as a result of microvascular

occlusion, and splenomegaly occurs in 60% of patients.

Hepatomegaly may also occur.

In pregnant patients, thrombosis may cause recurrent

spontaneous abortions.
 ET Diagnosis

WHO Diagnostic
Criteria
1. Sustained platelet
count > 600 x 109/L

2. Bone Marrow biopsy

showing proliferation
of mainly
megakaryocytes with
enlarged mature
nuclei
ET Clinical Course

Most remain stable with long Survival

Rates

Control and alleviation of symptoms

Rarely progresses to acute leukemias

Chronic Idiopathic
Myelofibrosis
Chronic Idiopathic Myelofibrosis (CIMF)
AKA:
Myelofibrosis with myeloid metaplasia
Agnogenic myeloid metaplasia
Primary myelofibrosis
Myelosclerosis with myeloid metaplasia
Myeloid megakaryocytic hepatopslenomegaly
Aleukemic myelosis
Essential Megakaryocytic Granulocytic
Metaplasia
CIMF

Chronic progressive panmyelosis with

intact maturation, progressive bone
marrow fibrosis, and splenomegaly with
multi-organ extramedullary hematopoiesis
CIMF: Incidence

Rare disease

Estimated to be 0.3 to 1.5 per 100 000

individuals per year (Ridell B et.al) (1/3 that of
CML).

Occurs > 50 ; most commonly in the 7th

decade (Sekhar M)

Men = Women (Tefferi A)

CIMF: Etiology

Unknown.

Myelofibrosis is secondary to release of

growth factors.

Extramedullary hematopoiesis seems to

be due to release of clonal stem cells
into the circulation.
CIMF: Clinical Features
Insidious onset
with weight loss,
anemia and

abdominal discomfort due to enlarging

spleen.

Often the liver is also enlarged:

results to jaundice.
portal hypertension in 10-20%
CIMF: Clinical Course

Fibrosis progressive anemia

Spleno-hepatomegaly
 CIMF: Clinical Course
Pre-fibrotic Phase
normocytic anemia
with poikilocytosis
including
dacrocytes,
nucleated red cells
thrombocytosis,
mild leukocytosis
with some
immature forms.
CIMF: Clinical Course

Pre-fibrotic Stage

Marrow is hypercellular

Contains abnormal
(with cloud-like
immature nuclei) and
small megakaryocytes
clustering around
sinuses and
trabeculae.
CIMF: Clinical Course

Fibrotic Stage

Marked peripheral
blood smear
anisopoikilocytosis

Splenomegaly is
typical
CIMF Clinical Course

Fibrotic Stage
Intense fibrosis
Bone marrow failure
Ineffective
erythropoiesis
hemolysis
CIFM Treatment

Corticosteroid and erythropoietin to control

anemia
Chronic
Lymphocytic
Leukemias
Chronic Lymphocytic Leukemia
(CML)
Rare under the age of 40; most cases
occur over the age of 60
M:F = 2:1
Onset is insidious
Signs and symptoms:
Maybe asymptomatic
Weakness, fatigue, anorexia, weight loss
Lymphadenopathy, splenomegaly
Chronic Lymphocytic Leukemia (AML)
Diagnosis:
Bone Marrow:
- Slight to moderate lymphocytosis

Other Organs
- Lymphocytes infiltrating to adjacent
lymphoid organs
Chronic Lymphocytic Leukemia (AML)
CLL: Goals of Treatment
The goals of CLL treatment are to
1. Slow the growth of CLL cells
2. Provide long periods of remission (when
there are no signs of CLL and/or people feel
well enough to carry on their day-to-day
activities)
3. Help people to feel better if they have
infections, fatigue or other symptoms.
Hairy cell leukemia,

AKA leukemic reticuloendotheliosis

Rare malignant disorder.

Usually occurs in middle-aged patients over 50.

The first symptoms of disease include

weakness and lethargy. Enlarged spleen occurs
in 80% of patients.
Hairy Cell Leukemia (HCL)

- B-cell disease, and the abnormal cell has

hairlike cytoplasmic projections on its
surface.
- Abnormal cell is a clonal B-cell lymphocyte
- Positive for acid phosphatase and
resistant
to tartrate
Hairy Cell Leukemia (HCL)

Fine, irregular
pseudopods and
immature nuclear
features.