2

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It is rare before 40 years of age, the median age of onset being 50-60 years. It accounts for almost 50% of Leukaemias occurring after the age of 60 years .in most cases the initial leukaemic proliferation is readily controlled by drugs, but many patients with CLL remain well without treatment.

Blood Picture

The outstanding feature is a marked increase in leucocytes ,often 100x10^9/l or higher ,nearly all are mature small lymphocytes .although the disease appears to originate in marrow ,pancytopenia is a late feature .however ,autoimmune hemolytic anemia & thrombocytopenia occur as early complications in about 10% of the cases .


In CLL 95%of cases are of B cell & 5% of T cell ,the leukaemic B cells possess surface immunoglobulns (sIg) and show light chain restriction express CD19 and CD 20 antigens.

Diagnosis

1. A persistent circulating lymphocyte count of >5x10^9/l. 2. BM lymphocytosis >30%.

Course

The clinical course is extremely variable: it may be rapidly progressive with a fatal outcome in 1-2 years or it may be static over decades.

Clinical Staging of CLL

Rai et al (1975) Stage 0 lymphcytosis of blood and marrow only. Stage 1 lymphocytosis and enlarged lymph nodes. Stage 2 lymphcytosis and enlarged liver or spleen or both with or without enlarged nodes. Stage 3 as with 0, 1&2 but Hb <11g/dl. Stage 4 as with 0, 1, 2, or 3 but Pl count < 100x 10^9 /l.


Hb>10g/dl. Pl>100x10^9/l Fewer than 3 sites of palpable organ involvement.
Good Prognosis,>10 years
A
Hb & pl as for A but 3 or more sites of palpable organ involvement.
Intermedi-ate
B
Hb <10g/l , pl<100x10^9/l.
Poor prognosis, <2years
C
Binet et al (1981)

While the commonest in adults of 30-40 years, the disease can occur at any age.

Introduction- CML
Etiology Not clear Little evidence of genetic factors linked to the disease Increased incidence Survivors of the atomic disasters at Nagasaki & Hiroshima Post radiation therapy

Clinical Features

Disease is biphasic, sometimes triphasic 40% asymptomatic Chronic phase Splenomegaly often massive Symptoms related to hypermetabolism Weight loss Anorexia Lassitude Night sweats

Clinical Features

Clinical features cont…Features of anaemiaPallor, dyspnoea, tachycardiaAbnormal platelet functionBruising, epistaxis, menorrhagiaHyperleukocytosis thrombosisIncreased purine breakdown : goutVisual disturbancesPriapism

Lab features

Peripheral blood film Anaemia Leukocytosis (usu >25 x 109/L, freq> 100 x 109/L WBC differential shows granulocytes in all stages of maturation Basophilia thrombocytosis

Lab features

Bone marrowHypercellular (reduced fat spaces)Myeloid:erythroid ratio – 10:1 to 30:1 (N : 2:1)Myelocyte predominant cell, blasts less 10%Megakaryocytes increased & dysplasticIncrease reticulin fibrosis in 30-40%

Lab features

Other lab features : NAP reduced Serum B12 and transcobalamin increased Serum uric acid increased Lactate dehydrogenase increased Cytogenetic : Philadelphia chromosome

Leukaemogenesis

Philadelphia chromosome is an acquired cytogenetic anomaly that is characterizes in all leukaemic cells in CML 90-95% of CML pts have Ph chromosome Reciprocal translocation of chromosome 22 and chromosome 9


Blood Picture
The outstanding feature is the gross circulating leucoytosis, some times exceeding 300x10^9/l.while many are mature neutrophil granulocytes, metamyelocyutes&myelocytesare always present. Basophilia. Anemia is generally moderate but increasing anemia & other features of marrow failure may indicate transformation to an acute phase . 75% of patients Myeloblastic. 25% Lymphoblastic usually (C ALL).

Differential Diagnosis: Pronounced reactive leucocytosis(Leukamoid Reaction)

Leukaemoid Reaction
CML
No or Occasional
High Proportion
Myelocytes
Normal Leucopoeisis
Absolute increase
Proliferative Marrow Cells
Increased
Low
Neutrophilic Alkaline Phosphatase
normal
Increased
Serum B12
_ve
+ve 90% _ve 10%
Ph Chromosome

Vit. B12 increase in CML because there is increase in vit. B12 plasma binding protein.