hematology

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Neoplastic proliferation of small mature appearing lymphocytes and account 25% of leukemia 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 .

Clinical features

Disease may be discovered incidentally -Fatigue, weakness, weight loss, anorexia, and/or recurrent infections may occur -Variable splenomegaly and nontender lymphadenopathy

CLL Physiicall Fiindiings

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%.

Bone Marrow in CLL

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)



Acquired genetic defect affect the pleuripotent stem cells. While the commonest in adults of 30-40 years, the disease can occur at any age.

Introduction- CML

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

Clinical Features

Clinical features related to …Hyperleukocytosis Increased purine breakdown : Gout Visual disturbance

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%


Lab features
Other lab features : 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 ( ALL).

Differential Diagnosis: Pronounced reactive leucocytosis(Leukamoid Reaction)