Chronic Leukemias

21/10/2019
 Types
2 main types
- Chronic Myeloid Leukemias (CML)

- Chronic Lymphoid Leukemias (CLL)

-
Chronic Myeloid Leukemia
• Chronic Myelogenous Leukemia

• Chronic Granulocytic Leukemia

 CML (Typical)
• An acqd abn of the haemopoietic stem cells present in all dividing granulocytic,erythroid,and
megakaryocytic cells in BM,in some B and probably T-lymphocytes
• a disease of middle age

• Normal BM is replaced by cells with an abnormal chromosome , the Philadelphia

Chromosome or Ph Chromosome.

• Philadelphia Chromosome is as a result of reciprocral translocation involving the long arms

Chromosomes 9 &22
• A chimeric BCR/ABL encoded for partly BCR (breakpoint cluster region) of chromosome 22
and partly by the ABL oncogene translated by chromosome 9 to 22
• BCR/ABL considerably enhances TPK activity
 Contd
• > 95% of cases are Ph +

• Ph- + BCR- ABL+ve arrangement may present like typical disease

• Ph- BCR- ABL –ve disease has atypical presentation

• Cells in all stages of granulocytic development are present in the

peripheral blood i.e Myeloblasts,Promyelocytes, Metamyelocytes,
bands and segmented neutrophils
 Phases
• 3 Phases – depends on % blast cells in the peripheral blood
- Chronic <5%

- Accelerated up to 12%

- Blast cell transformation> 50% cells are primitive blast forms

 Clinical Features
• Anaemia with features
• Bleeding disorders
• Visual disturbances due to retinal disease,priapism
• Hypermetabolism- anorexia, lassitude,weight loss, night sweats
• Massive Splenomegaly
• Neurological symptoms
• Skin infiltrates
• Some patients are discovered during routne blood counts
 Laboratory Features
• Normochromic normocytic anaemia
• Marked Leucocytosis >100,000* 10 9

• All cells of granulocytic maturation are seen in the peripheral film with a myelocyte –neutrophil peak.
Bospphilia, Eosinophilia

• Thrombocytosis

• BM – markedly hypecellular

• Hyperuricaemia –tumour lysis syndrome

• Reduced alkaline phosphatase

 Variants of Classical CML
• Ph- BCR –ABL –ve
- Fewer myelocytes, more monocytoid cells, atypical neutrophils in the peripheral blood,
severe anaemia, thrombocytopenia are more frequent than in the classical

Juvenille CML

Chronic Neutrophilic –rare. A diagnosis of exclusion

Eosinophilic leukemia

Chronic Myelomonocytic Leukemia CMML

 Blast Cell Transformation
• In 70% of cases, there is terminal transformation >> Acute Leukaemia
>> BM failure

• Transformation could be Myeloblastic, Lymphoblastic, mixed or rarely

Megakaryoblastic
 Leukaemoid Reaction
• Differential diagnosis
Excessive reactive leukocytosis
Presence of cytoplasmic granulations and Dohle bodies
-elevated alkaline phosphatase score
- Occasional lymphocyte reaction occurs
- Toxic granulations,Dohle bodies
- High neutrophil alkaline phosphatase score.differentiates it from
- CML with low score, high myelocte count and positive Philadelphia
chromsome
 Treatment
• TKI inhibitor e.g Imatinib TK formed by BCR-ABL fusion gene in CML. Controls the
WCC and converts the marrow to partial or 100% Ph-

• Hydroxyurea- controls WCC and prolongs the chronic phase

• Alpha interferon
• Alllopurinol- Prevents high urate production which may cause gout or renal damage

• Stem cell transplantation –for younger patients and HLA matching siblings,
unrelated HLA matched donors, autologous stem cell transplants