1. Chronic leukemias
CML
CLL
MDS

2. Chronic myeloid leuk. (CML)
Comprises less than 20% of all leuk. & is seen most frequently in middle age .In more than 95% of patients there is replacement of normal Bone Marrow (BM) by cells with abnormal chromosome (Philadelphia or Ph chromosome)

3. Philadelphia chromosome:
is abnormal chromosome 22 due to translocation of part of long arm (q) of chromosome 22 to another chromosome ,usually 9 , with translocation of part of chromosome 9 including ABL oncogene to chromosome 22
It is aquired abnormality of haemopoietic stem cells that present in all dividing granulocytes, erythroid & megakaryocytic cells also in some B & minority of T lymphocytes .

4. Philadelphia chromosome:

6. Clinical features: This disease occure in either sex M:F= 1.4:1
Moat frequently between the age of 40-60y .It may occurs in children & neonates & very old
There is no predisposing factor but the incidence was increased in Japan after exposure to atomic bomb.
1-Symptoms of hypermetabolism e.g. weight loss, lassitude, anorexia or night sweat.
2- Splenomegaly is nearly always present & is frequently massive.

7. Clinical features 3- Features of anemia
4- Bruising, epistaxis, menorrhagia due to abnormal platelet function.
5- Gout or renal impairment due to hypercalcaemia from excessive purine breakdown
6- Rare symptoms include visual disturbances & priapism.

10. Lab. Findings:
1- Leucocytosis: is usually >50×109/L & some times >500×109/L . A complete spectrum of myeloid cells is seen in peripheral blood, the level of neutrophils & myelocytes exceed those of blast & promyelocytes
2- Ph chromosome on cytogenic analysis of blood or BM
3- BM is hyper cellular with granulopoietic predominance.

12. Lab. Findings: 4- Neutrophil alkaline phosphatase score is low
5- Increased circulating basophiles
6- Normochromic normocytic anemia
7- Platelets count may be increased, normal or decreased
8- Serum B12 & B12 binding capacity increased
9- Serum uric acid increased

13. Chronic lymphocytic leuk.(CLL)
Account for 25% or more of leuk. seen in clinical practice & occurs chiefly in the elderly.
The accumulation of large numbers of lymphocytes to times the normal lymphoid mass in the blood, BM, spleen, lymph nodes & liver. The cells are monoclonal population of B- lymphocytes. T- cell chronic leuk. is uncommon.

14. Classification of chronic lymphoid leuk
B-cell CLL
1-B-CLL
2-B-PLL
3-HCL
4-PCL
T-cell CLL
1-T-CLL
2-T-PLL
3-Adult T- cell leuk./lymphoma.

15. Clinical features:
1- The disease occurs in older subjects & is rare before 40 y
The M: F= 2:1
2- Symmetrical enlargement of superficial lymph nodes, the nodes are usually discrete & non tender.
3-Features of anemia may be present
4- Splenomegaly &hepatomegaly are usual in late stages
5- Bacterial or fungal infections are common in late stages

16. Clinical features
6- Patient with thrombocytopenia may show bruising or purpura.
7- Excessive reaction to vaccination & insect bite may occur
8- Skin infiltration is present in small number of patients
9-Tonsillar enlargement may be a feature
10- Many cases are diagnosed when routine blood test is performed (accidentally)

18. Lab. Findings
1- lymphocytosis : the absolute lymphocyte count is>5×109/L & may be up to 300 or more . between 70-99% of white cells in blood film appear as small lymphocytes .Smudged or smear cells are also present.

20. 2- Normochromic ,normocytic anemia is present in late stages due to:
BM infiltration
Hypersplenism
Autoimmune hemolytic anemia

21. Lab. Findings 3- Thrombocytopenia occurs in many patients
4- BM aspirate shows lymphocytic replacement of normal marrow elements. Lymphocytes comprise 25-95% of all cells
5-reduced concentration of S.Ig & this becomes more marked with advanced disease.
6-Trisomy12 or t (11:14) are the most frequent chromosome findings

22. Course & prognosis. CLL divided into 5 stages according to Rai classification
Low levels of platelets
Anemia
Enlarged spleen or liver
Swollen lymph nodes
High levels of lymphocytes
Ray Stage No
Yes I
Yes or no II
III IV

23. These stages correlate with different prognosis
e.g. Rai 0 with mean survival of 12 y
Rai 1 with mean survival of 8 y

24. The international working classification (Binet)
Low levels of platelets
Anemia
Number of lymph node areas
Binet stage no
Less than 3 A
3 or more B
Yes (or anemia)
Yes (or low platelets)
Any number C

25. Myelodysplastic syndromes (MDS)
A large group of acquired neoplastic disorders of BM ,
most common in elderly & characterized by increased BM failure with quantitative & qualitative abnormalities of all 3 myeloid cell lines (red cells, granulocyte/monocyte &platelets )
due to defect of stem cells & ineffective haemopoiesis so that cytopenias often accompany a marrow of normal or increased cellularity.
In most cases , the disease arises de novo , but in significant proportion chemotherapy &/or radiotherapy has previously been given for another hematological diseases.

26. Classification BM Peripheral blood 50 Blast<5% Blast <1%
Survival (Ms) BM
Peripheral blood 50
Blast<5%
Blast <1%
Refractory anemia(RA)
Blast<5% ring sidroblasts >15% of total erythroblasts
Refractory anemia with ring sidroblast (RARS) 11
Blast 5-20 %
RA with excess blast(RAEB) 5
Blast 20-30% or auer rods
Blast>5%
RAEB with transformation (RAEB-t)
Any of the above with promonocytes
Any of the above with >1×10/L monocytes
Chronic myelomonocytic leuc.(CMML)

28. Clinical features
50% of patients are >70 years, &<25% are <50 y old.
-Male are more commonly affected.
- The evolution is often slow & the disease may be found by chance
-The symptoms if present are that of anemia, infections or of easy bruising or bleeding.

29. Clinical features
-In some patients, transfusion dependant an. dominates the course. While in others recurrent infection or spontaneous bruising or bleeding is the major clinical problem.
-Neutophils, monocytes & platelets are often functionally impaired lead to spontaneous infections, bruising or bleeding regardless the severity of cytopenias.
-The spleen is not usually enlarged except in CMML in which gum hypertrophy & lymphadenopathy may occur.

30. Lab. Findings: 1- peripheral blood:
pancytopenia is frequent finding
The red cells are usually macrocytic or dimorphic but occationally hypochromic , normoblast may be present., the reticulocyte count is low .
Granulocytes are often reduced &may show lack of granulation .Their chemotactic,phagocytic &adhesive function are impaired. The pelger abnormality (single or bilobed nucleus) is often present. In CMML, monocytes are>1×109/L in the blood & total WBC >100×109/L .
The platelets may be unduly large or small & are usually decreased in number but in 10% of cases are elevated.
In poor prognosis cases myeloblasts are present in blood

31. 2-BM:
the cellularity is usually increased, ring sidroblast may occur in all 5 FAB types, but by definition they are>15% in RARS
Multinucleated normoblasts & other dyserythropoietic features are seen
The granulocyte precursors show defective primary & secondary granulation
Megakaryocytes are abnormal with micto , small binuclear or polynuclear forms
BM biopsy shows fibrosis in 10% of cases.

32. 3-Chromosomal & oncogene abnormalities:
Cytogenic abnormalities are more frequent in secondary than primary MDS & most commonly constitute partial or total loss of chromosome 5,7,Y or trisomy 8
RAS oncogene (N-RAS) mutation occur in 20% of cases
FMS mutation occur in 15% of cases