CHRONIC LYMPHOCYTIC LEUKEMIA

Question 1

INTRO

Answer 1

CLL is a clonal B-cell malignancy characterized by accumulation of malignant lymphocytes in the bone marrow and blood

A disease of the elderly, common in the western world and more in males than females

Question 2

Clinical features

Answer 2

Symptoms are due to
1. Organ filtration
Lymphadenopathy
Splenomegaly and hepatomegaly

2. Bone marrow suppression
   Symptoms and signs of anemia (Pts are prone to Autoimmune hemolytic anemia AIHA)
   Recurrent infections (due to hypogammaglobulinaemia and neutropenia)
   Bleeding caused by Thrombocytopenia
   (AIHA + ITP = Evans Syndrome)

ITP is immune Thrombocytopenic purpura

Question 3

Differential Diagnosis

Answer 3

Small Lymphocytic Lymphoma (SLL) - Tissue equivalent of Cll

Hodgin Lymphoma

Non Hodgkin Lymphoma

ProLymphocytic Leukemia

Hairy Cell Leukemia

Question 4

Diagnostic Investigations

Answer 4

Definitive and Supportive

Definitive Investigations:
1. Full Blood Count: Normocytic Normochromic anaemia, Thrombocytopenia and the absolute lymphocytosis can be observed

2. Blood Film: Typically CLL cells are Small, mature looking lymphocytes and scanty cytoplasm
3. Bone Marrow Aspiration: Shows up to 95% lymphocytic replacement of normal marrow elements
4. ImmunoPhenotyping: to detect CD markers on cells to identify its lineage, Normally CLL cells are CD5, CD19 and CD 23

5. Cytogenetics: To detect Translocations Inversions and Deletions
CLL shows
Trisomy 12
Deletion 11q23
Deletion 17p
Deletion 13q14

Supportive Investigations include:
Clotting profile
Serum E,U,Cr
Blood sugar
Liver function tests
Renal function tests

Question 5

STAGING

Answer 5

Rai Classification and Binet Classification
Rai Classification
Stage 0-4
Stage 0- absolute lymphocytosis (>5 x 10/L)
Stage 1- Stage 0 + enlarged lymph nodes (adenopathy)
Stage 2- Stage 0 +/- adenopathy + organomegaly
Stage 3- Stage 0 + Anaemia +/- organomegaly and adenopathy
Stage 4- Stage 0 + thrombocytopenia (<100 x10/L) +/- adenopathy and organomegaly

Binet Classification 
Stage A (50-60%)- Organ enlargement in 0,1 or 2 areas , Platelets and Haemoglobin  >/=100

Stage B (30%)- Organ enlargement in 3,4 or 5 areas

Stage C (<20%)- Organ enlargement not considered, Haemoglobin and Platelets <100

Question 6

Treatment

Answer 6

Supportive and Definitive
Supportive
-Counselling
-Nutritional support
-IV fluid administration 
-Blood and Blood Products 

Definitive
Indications for definitive treatment

Rapid lymphocyte doubling time (doubling time <6 months)
•Persistent systemic symptoms: fever, weight loss and drenching night sweats
•Massive symptomatic peripheral lymphadenopathy
•Progressive and painful splenomegaly
•Marrow disease with anaemia ± thrombocytopaenia

Treatment includes

Corticosteroids eg Prednisolone
•Alkylating agents e.g Chlorambucil, cyclophosphamide
•Nucleoside analogues e.g. Fludarabine, Deoxycoformycin
•Monoclonal antibody e.g. Rituximab (anti CD20), Alemtuzumab (anti CD52), Ofatumumab and Obinutuzumab (