This document discusses several types of hematological malignancies: - Myeloproliferative neoplasms (MPNs) are diseases where stem cells are affected, causing increased proliferation of blood cells. Specific types include polycythemia vera (excess red blood cells), essential thrombocytosis (excess platelets), and primary myelofibrosis. - Chronic myeloid leukemia (CML) is characterized by the Philadelphia chromosome and progresses through chronic, accelerated, and blast crisis phases without treatment. - Chronic lymphocytic leukemia (CLL) involves the accumulation of abnormal B lymphocytes. It typically affects older adults and can cause infections, anemia, and lymph node enlargement.

1. Haematological malignancies 2
Dr. Ousama Haider

2. Myeloproliferative neoplasm
(MPN)
Myeloproliferative neoplasm (MPN) is a group of
interacting diseases where bone marrow stem
cells are affected (by an acquired abnormality)
which result in increase proliferation
It can affect any cell lineage:
- When red cells’ precursor is affected: polycythemia
Vera
- When platelets are affected: essential
thrombocytosis
- When all three lineages are affected: primary
myelofibrosis

5. Myeloproliferative neoplasm
(MPN) features
• Cytosis.
• Organomegaly (mainly splenomegaly).
• High uric acid. Because of increased turnover of these
cells - may cause gout Hypercellular bone marrow.
• Clonal evolution.
• Progression to acute leukemia ,mainly (Acute
Myeloid Leukemia).

6. Polycythemia
• Absolute increase in total body red cell volume
(or mass).
• Manifests itself as a raised hemoglobin or
packed cell volume (PCV).
• Polycythemia Vera:
It is a type of MPN characterized by increased red
blood cell production independent
of the mechanisms that normally regulate
erythropoiesis.
Almost always, accompanied with JAK2 mutation.

8. Diagnostic features of polycythemia
vera:
Major criteria
1. HB >16.5g/dl in men, 16.0g/dl in women. (raised
Hb). Hematocrit > 49% in men or >48% in women
2. Hypercellular bone marrow (pan-myelosis all
myelo cell lineages may be increased).
3. JAK2 mutation in >95% of cases.
Minor criteria
1. No increase in serum erythropoietin level
(Subnormal) Because it is not the cause.
When do we say that this patient has PV?
• When he has 3 Major criteria or First 2 Major and the Minor
criteria.

9. Clinical feature of polycythemia Vera :
1-Increased blood viscosity due to increase the
number of RBCs related to plasma.
• Hypertension
• Headache, dizziness, visual disturbances & paresthesia
• pruritus.
2- Thrombosis
• Deep vein thrombosis
• Myocardial infarction
• Mesenteric, portal or splenic vein thrombosis
3-Splenomegaly in 70% most important feature due
to Extra destruction of RBCs in the
spleen, because of its high number
4-Hepatomegaly in 40%

10. Investigations of polycythemia vera :
• CBC:
RBC: increased *Hb: increased
WBC&PLT (platelets) :mildly increased (usually).
• Blood smear:
Excess of normocytic normochromic RBC.
• ± Leukocytosis &thrombocytosis.
• Bone marrow
Hypercellular.
Predominant erythroid precursors.
± Increased megakaryocytes & myeloid precursors.

12. Complication and treatment of
polycythemia vera:
Treatment:
• Venesection+ Aspirin to prevent thrombosis
• ± Myelo-suppressive drugs (hydroxyurea) it’s a
chemotherapy
10-15 years

13. Essential
Thrombocythemia
It is a MPN that involves primarily the
megakaryocytic lineage and characterized by
sustained thrombocytosis.
Diagnostic features of Essential Thrombocythemia:
• Sustained thrombocytosis ≥45O×10⁹/L.
• Hypercellular BM with megakaryocytic
proliferation.
• Exclusion of: CML, MDS, PV &PMF. (all these
diseases can cause thrombocytosis so exclude them)

15. Clinical presentation of essential
thrombocytopenia
• Asymptomatic (50%)
• Thrombosis
• Bleeding (defective function of platelets)
• Mild splenomegaly (50%)
• Mild hepatomegaly (20%)
Treatment : Aspirin (to prevent thrombosis) ±
Hydroxyurea

16. Chronic myeloid
leukaemia
• 20% of all leukaemias
• myeloproliferative stem cell disorder resulting in
proliferation of all haematopoietic lineages but
manifesting predominantly in the granulocytic
series.
• Maturation of cells proceeds fairly normally.
• The disease occurs chiefly between the ages of
30 and 80 years, with a peak incidence at 55
years.
• The defining characteristic of CML is the
chromosome abnormality known as the
Philadelphia (Ph) chromosome

17. The disease has three phases:
• chronic phase: the disease is responsive to
treatment and is easily controlled,
introduction of imatinib therapy
• accelerated phase (not always seen), in
which disease control becomes more difficult
• Blast crisis, in which the disease transforms
into an acute leukaemia, either myeloblastic
(70%) or lymphoblastic (30%), which is
relatively refractory to treatment. the cause of
death, imatinib therapy reduce transforms

18. Clinical features
• lethargy, weight loss, abdominal
discomfort, gout(UA) and sweating,
• 25% of patients are asymptomatic at
diagnosis.
• Splenomegaly is present in 90%,
Hepatomegaly occurs in about 50%.

19. Investigations
CBC :
• normocytic, normochromic anaemia.
• leucocyte count can vary from 10 to 600 × 109/L.
• very high platelet count, sometimes as high as 2000 × 109/L.
In the blood film,
• the full range of granulocyte precursors, from myeloblasts to mature
neutrophils, is seen but the predominant cells are neutrophils and
myelocytes ,Myeloblasts usually constitute less than 10% of all white
cells. There is often an absolute increase in eosinophils and basophils,
and nucleated red cells are common
• accelerated phase, the percentage of more primitive cells increases.
Blast transformation is characterised by a dramatic increase in the
number of circulating blasts
• Blood LDH levels are elevated and the uric acid level may be high
due to increased cell breakdown.
• Bone marrow should be obtained to confirm the diagnosis and phase
of disease by morphology, chromosome analysis Ph chromosome

20. Management
Chronic phase : tyrosine kinase inhibitors (TKIs) for the treatment of
CML
First-line
• Imatinib• Nilotinib• Dasatinib
Second-line
• Imatinib• Nilotinib• Dasatinib• Bosutinib• Ponatinib*
• They usually normalise the blood count within a month and within3–6
months produce complete cytogenetic response(disappearance of the
Ph chromosome) in some 90% of patients.
• A sample of bone marrow is taken at 6 months to confirm complete
cytogenetic response, and patients are subsequently monitored by 3-
monthly
Accelerated phase and blast crisis: Management is more difficult
• chemotherapy with tyrosine kinase inhibitors (TKIs)

21. Chronic lymphocytic
leukaemia
• the most common variety of leukaemia,
accounting for 30% of cases
• median age at presentation is 65–70 years
• B lymphocytes, which would normally
respond to antigens by transformation and
antibody formation, fail to do so. An ever-
increasing mass of immuno-incompetent cells
accumulates, to the detriment of immune
function and normal bone marrow
haematopoiesis.

22. Clinical features
• anaemia, infections, painless
lymphadenopathy, and systemic
symptoms such as night sweats or weight
loss

23. Investigations
• The diagnosis is based on the peripheral blood
findings of a mature lymphocytosis (> 5 × 109/L) with
characteristic morphology and cell surface markers.
• Immunophenotyping reveals the lymphocytes to be
monoclonal B cells expressing the B-cell antigens
CD19 and CD23, with either kappa or lambda
immunoglobulin light chains and, characteristically, an
aberrant T-cell antigen CD5
• Bone marrow examination is not essential for the
diagnosis of CLL, may be helpful in difficult cases, for
prognosis and monitor response to therapy

24. Staging of chronic lymphocytic leukaemia
Clinical stage A (60% patients)
• No anaemia or thrombocytopenia and fewer than
three areas of lymphoid enlargement
Clinical stage B (30% patients)
• No anaemia or thrombocytopenia, with three or
more involved areas of lymphoid enlargement
Clinical stage C (10% patients)
• Anaemia and/or thrombocytopenia, regardless of
the number of areas of lymphoid enlargement

25. Management
• Treatment is required only if :evidence of bone marrow failure,
massive or progressive lymphadenopathy or splenomegaly,
systemic symptoms, increasing lymphocyte count, autoimmune
haemolytic anaemia or thrombocytopenia
• Initial therapy for those requiring treatment (progressive stage A and
stages B and C) is based on the age and fitness of the patient and the
TP53 mutation status
• For patients who are under 70 years, fit and TP53 mutation negative,
fludarabine in combination with the alkylating agent cyclophosphamide
and the anti-CD20 monoclonal antibody rituximab (FCR) is standard
care.
• Recently, a more potent type 2 anti-CD20antibody, obinutuzumab, has
become available and produces better responses in combination with
chlorambucil than rituximab.
• Bone marrow failure or autoimmune cytopenias may respondto
glucocorticoid treatmen
• Supportive care: transfusions, Radiotherapy may be used for
lymphadenopathy, causing discomfort or local obstruction,
Splenectomy