What are Leukemias

Neoplasm of white blood cell and its precursor

Clonal proliferations and accumulation of cells in marrow

Classify as

· Acute leukaemias

· Chronic leukaemias

Types of Leukaemia

Introduction- CML

· Clonal malignant myeloproliferative disorder characterized by increased proliferation of the granulocytic cell line without the loss of their capacity to differentiate

· Results in increases in myeloid cells, erythroid cells and platelets in peripheral blood and marked myeloid hyperplasia in the bone marrow

· Originate in a single abnormal haemopoietic stem cell

· Incidence :1 per 100,000 (UK)

· Accounts for 7-15% of all leukaemia in adults

· Median age : 53 years

· All age groups, including children, can be affected


· Not clear

· Little evidence of genetic factors linked to the disease

· Increased incidence

o Survivors of the atomic disasters at Nagasaki & Hiroshima

o Post radiation therapy


· 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

· BCR (breakpoint cluster region) gene on chromosome 22 fused to the ABL (Ableson leukemia virus) gene on chromosome 9

· Ph chromosome is found on myeloid, monocytic, erythroid, megakaryocytic, B-cells and sometimes T-cell proof that CML derived from pluripotent stem cell

· Molecular consequence of the t(9;22) is the fusion protein BCR–ABL, which has increased in tyrosine kinase activity

· BCR-ABL protein transform hematopoietic cells so that their growth and survival become independent of cytokines

· It protects hematopoietic cells from programmed cell death (apoptosis)

Clinical Features

o Disease is biphasic, sometimes triphasic

o 40% asymptomatic

o Chronic phase

o Splenomegaly often massive

o Symptoms related to hypermetabolism

o Weight loss

o Anorexia

o Lassitude

o Night sweats

o Features of anaemia

o Pallor, dyspnoea, tachycardia

o Abnormal platelet function

o Bruising, epistaxis, menorrhagia

o Hyperleukocytosis

o thrombosis

o Increased purine breakdown : gout

o Visual disturbances

o Priapism

o Lab features

o Peripheral blood film

o Anaemia

o Leukocytosis (usu >25 x 109/L, freq> 100 x 109/L

o WBC differential shows granulocytes in all stages of maturation

o Basophilia

o thrombocytosis

o Bone marrow

o Hypercellular (reduced fat spaces)

o Myeloid:erythroid ratio – 10:1 to 30:1 (N : 2:1)

o Myelocyte predominant cell, blasts less 10%

o Megakaryocytes increased & dysplastic

o Increase reticulin fibrosis in 30-40%

o Other lab features :

o NAP reduced

o Serum B12 and transcobalamin increased

o Serum uric acid increased

o Lactate dehydrogenase increased

o Cytogenetic : Philadelphia chromosome

Laboratory- summary

Lab investigation to confirm diagnosis

Full blood picture

Neutrophil alkaline phosphatase

Bone marrow cytogenetic


Accelerated phase

Median duration is 3.5 – 5 yrs before evolving to more aggressive phases

Clinical features

Increasing splenomegaly refractory to chemo

Increasing chemotherapy requirement

Lab features

Blasts>15% in blood

Blast & promyelocyte > 30% in blood

Basophil 20% in blood


Cytogenetic: clonal evolution


Blastic phase

Resembles acute leukaemia

Diagnosis requires > 30% blast in marrow

2/3 transform to myeloid blastic phase and 1/3 to lymphoid blastic phase

Survival : 9 mos vs 3 mos (lym vs myeloid)

General Management

o Discussion with family

o The disease & diagnosis

o Prognosis

o Choices of treatment

§ Cytotoxic drug vs bone marrow transplant

§ Side effect

o CML - principles of treatment

o Relieve symptoms of hyperleukocytosis, splenomegaly and thrombocytosis

o Hydration

o Chemotherapy (bulsuphan, Hydoxyurea)

o Control and prolong chronic phase (non-curative)

o alpha interferon+chemotherapy

o imatinib mesylate

o chemotherapy (hydroxyurea)

o CML - principles of treatment

o Treatment cont…

o Eradicate malignant clone (curative)

o allogeneic transplantation

o alpha interferon ?

o imatinib mesylate/STI 571 ?(Thyrosine kinase inhibitor)

o Chemotherapy

o Busulphan

o Alkylating agent

o Preferred in older pts (not candidate for transplant)

o Side effect :

§ prolonged myelosuppression

§ Pulmonary fibrosis

§ Skin pigmentation

§ infertility

o Chemotherapy

o Hydoxyures

o Fewer side effect

o Acts by inhibiting the enzyme ribonucleotide reductase

o Haematological remissions obtain in 80% for both drugs

o However disease progression not altered and persistence of Ph chromosome containing clone

o Chemotherapy

o Recombinant human α- Interferon

o Prolong chronic phase and increase survival

o Haematogical and cytogenetic remission

o Side effect

§ Flu like symptoms

§ Fever and chills

§ Anorexia

§ Depression

o CML - prognosis

o Median survival 3.5 yrs (range 2-8 yrs)

o Interferon + chemotherapy :6 years

o Transplant : 5+ years

o imatinib mesylate ?

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