Hematology myeloid neoplasm

1. MIELOPROLIFERATIVE
DISORDERS
Dr : Walaa Mamoun ALsafi

2. MYELOPROLIFERATIVE
DISORDERS (MPD)
MPD are clonal diseases originating in
pluripotential haematopoietic stem cell.
The clonal expansion results in increased and
abnormal haematopoiesis and produces a
group of interrelated syndromes, classified
according to the predominant phenotypic
expression of the myeloproliferative clone.

3. CHRONIC MYELOPROLIFERATIVE
DISORDERS (MPD)
Neoplastic (clonal) disorders of hemopoietic
stem cells
Over-production of all cell lines, with usually
one line in particular
Fibrosis is a secondary event
Acute Myeloid Leukemia may occur

4. Rationale for classification
Classification is based on the lineage of the
predominant proliferation
Level of marrow fibrosis
Clinical and laboratory data (BPF, BM,
cytogenetic & molecular genetic)

5. Myeloproliferative disorders
WHO Classification of CMPD
Ch Myeloid leukemia
Ch Neutrophillic leukemia
Ch Eosinophillic leukemia / Hyper Eo Synd
Polycythemia Vera
Essential Thrombocythemia
Myelofibrosis
CMPD unclassifiable

6. Myeloproliferative disorders
Ch Myeloid leukemia (BCR-ABL positive)
Polycythemia Vera
Essential Thrombocythemia
Myelofibrosis
– Specific clincopathologic criteria for diagnosis
and distinct diseases, have common features
– Increased number of one or more myeloid cells
– Hepatosplenomegaly
– Hypercatabolism
– Clonal marrow hyperplasia without dysplasia
– Predisposition to evolve

7. Bone marrow stem cell
Clonal abnormality
Granulocyte
precursors
Red cell
precursors
Megakaryocytes Reactive
fibrosis
Essential
thrombocytosis
(ET)
Polycythaemia
rubra vera
(PRV)
Myelofibrosis
AML
Chronic myeloid
leukemia
70%
10% 10%
30%

8. POLYCYTHEMIA VERA

9. POLYCYTHEMIA VERA
Chronic, clonal myeloproliferative disorder
characterized by an absolute increase in
number of RBCs
2-3 / 100000
Median age at presentation: 55-60
M/F: 0.8:1.2

10. POLYCYTHEMIA VERA (PV)
(Polycythaemia rubra vera)
Definition of polycythemia
Raised packed cell volume (PCV / HCT)
Male > 0.52 (52%)
Female > 0.48 (48%)
Classification
Absolute
Primary proliferative polycythaemia (polycythaemia vera)
Secondary polycythaemia
Idiopathic erythrocytosis
Apparent
Plasma volume reduced but no red cell mass changes

11. 11
ERYTHROCYTOSIS (Classification)
I. Absolute erythrocytosis (Polycythemia):
A. Secondary erythrocytosis (abnormal increase of serum
erythropoietin level)
1. Erythrocytosis secondary to decreased tissue oxygenation:
a) chronic lung diseases
b) cyanotic congenital heart diseases
c) high-altitude erythrocytosis
d) hypoventilation syndromes
- carboxyhemoglobin in „smoker’s polycythemia”

12. POLYCYTHEMIA VERA (PV)
Clinical features
Age
– 55-60 years
– May occur in young adults and rare in childhood
Symptoms common to all erythrocytosis
– Headache, mental acuity, weakness
Symptoms more specific to P vera and myeloproliferative
diseases.
– Pruritis after bathing
– Erythromelalgia
– Hypermetabolic symptoms
– Thrombosis (arterial or venous)
– Hemorrhage

13. POLYCYTHEMIA VERA
physical examination
1. Splenomegaly – is present in 75% of patients at the
time of diagnosis.
2. Hepatomegaly - is present in approximately 30% of
patients at the time of diagnosis.
3. Hypertension
4. On examination of the eye grounds, the vessels may be
engorged, tortuous, and irregular in diameter; the veins
may be dark purple.
Facial plethora

14. POLYCYTHEMIA VERA
physical examination
Hepatosplenomegaly
Erythromelalgia
– Increased skin temp
– Redness
Liver
40%
Spleen
70%
Erythromelalgia

15. PRV - DIAGNOSIS
exclude secondary polycythemia
look for features of primary polycythemia
measure erythropoietin
JAK-2 mutation analysis

16. POLYCYTHEMIA VERA
Lab Findings
CBC
– Hgb/Hct
– WBC in 45%
– Plts in 65%
– Basophilia (seen in all MPDs)
 Uric acid (can lead to gout)
Positive JAK2 V617F mutation in about 97 percent of
patient

17. JAK2 Mutation
JAK2 :is gene in short arm of chromosome 9
that encoded cytoplasmic tyrosine kinase
activity which increase cellular proliferation
and cell survival
Abnormal signalling in PV through JAK2 was
first proposed in 2004
a single nucleotide JAK2 somatic mutation
(JAK2V617F mutation) in the majority of PV
patients

20. PV - TREATMENT
Phlebotomy
Myelosuppressive agents
– Hydroxyurea
– Alkylating agents
Interferon alpha

21. 21
POLYCYTHEMIA VERA
Antiplatelets agents
Aspirin initially 150-300mg/d,
maintence therapy 75-100 mg
Special Topics
1. Pruritus:antihistaminic agent
2. Hyperuricemia-allopurinol 300mg/day

22. ESSENTIAL
THROMBOCYTHEMIA (ET)

23. THROMBOCYTOSIS
Etiology of Thrombocytosis
Primary - if the thrombocytosis is caused by a
myeloproliferative neoplasm, the platelets are frequently
abnormal and the patient may be prone to both bleeding and
clotting events.
Secondary - if thrombocytosis is secondary to another disorder
(reactive), even patients with extremely high platelet counts
(e.g., > 1,000,000 cells/μl) are usually asymptomatic.
Definition: thrombocytosis is defined as a platelet count > 450,000 cells/μL

25. 25
ESSENTIAL THROMBOCYTHEMIA
(ET)
ET is a clonal myeloproliferative disorder
characterized by bone marrow hyperplasia
with excessive proliferation of
megakaryocytes and sustained elevation of
the platelet count.

26. ESSENTIAL
THROMBOCYTHEMIA (ET)
Neoplastic stem cell disorder causing
dysregulated production of large numbers of
abnormal platelets
Abnormal platelets aggregate, causing
thrombosis
Abnormal platelets also cause bleeding

27. 27
ESSENTIAL THROMBOCYTHEMIA
clinical picture
1. Thrombotic complications (intermittent or permanent occlusion of small
blood vessels)
transient cerebral ischemic episodes that may progress to
infarction
peripheral arterial occlusive disease associated with erythromelalgia”
2. Hemorrhagic complications - bleeding after surgery and spontaneus upper
gastrointestinal bleeding
3. Splenomegaly - 20-50% patients
4. Hepatomegaly - rarely

28. 28
ESSENTIAL THROMBOCYTHEMIA
laboratory findings
Thrombocytosis (in most patients patients>1000 G/l)
Numerous thrombocyte aggregates in peripheral blood
smear
Leukocytosis, usually less than 20
Neutrophilia and a mild shift to the left(usually to
metamyelocyte)
Slight eosinophilia and basophilia
Marked hyperplasia of the megakaryocytes in the BM
JAC 2 mutain in about 50 of patient

30. ET - OUTCOMES
Most patients with ET enjoy a normal life expectancy
Like PV, the major risks are secondary to thrombosis and disease
transformation:
▪ 15-year cumulative risks:
▪ thrombosis - 17% risk
▪ clonal evolution into either myelofibrosis (4%) or AML (2%)
High risk for thrombosis:
▪ age ≥ 60
▪ prior thrombosis
▪ long-term exposure to a plt count of > 1,000,000

31. MYELOFIBROSIS

32. MYELOFIBROSIS
Clonal stem cell disorder affecting megakaryocytes
predominantly
All myeloproliferative disorders can result in a spent phase
which can be difficult to distinguish from primary MF

33. MYELOFIBROSIS
Myelofibrosis is a chronic myeloproliferative disease with
clonal hematopoesis and secondary(non-clonal)
hyperproliferation of fibroblasts (stimulated by PDGF, TGF-
released from myeloid cells, mainly from neoplastic
megakaryocytes) with increased collagen synthesis. It
produces bone marrow fibrosis and to extramedullary
hematopoesis in the spleen or in multiple organs

34. MYELOFIBROSIS
Insidious onset in older people
– asymptomatic (15% - 30%)
– severe fatigue
Splenomegaly- massive
Hepatomegaly
Hypermetabolic symptoms
– Loss of weight, fever and night
sweats
Bleeding problems
Bone pain
Gout
Can transform to acute
leukaemia in 10-20% of cases

35. MYELOFIBROSIS
Anaemia
High WBC at presentation
Later leucopenia and
thrombocytopenia
Leucoerythroblastic blood film
Tear drops red cells
Bone marrow aspiration- Failed
due to fibrosis
Trephine biopsy- fibrotic
hypercellular marrow
JAK2+ (V617F) in
approximately 50% of cases

36. Pathological Features of Peripheral Blood and Bone
Marrow in Patients with Myelofibrosis with Myeloid
Metaplasia

37. MF - OUTCOME
 As fibrosis progresses, cytopenias worsen leading to a
transfusion dependency
▪ symptoms related to extrmedullary hematopoiesis increase
(worsening splenomegaly) also frequently identified

38. 38
MYELOFIBROSIS
- prognosis
- a median survival of 3,5 to 5,5 years
- the principal causes of death are infections,
thrombohemorrhagic events, heart failure, and
leukemic transformation
- leukemic transformation occurs in
approximately 20% of patients during first 10
years