Chronic myelogenous leukaemia

Chronic myelogenous leukaemia

Definition

Chronic myelogenous leukaemia (CML) is a myelopro-liferative disorder arising from clonal proliferation of haemopoietic stem cells giving rise to a high peripheral white blood cell count.

Incidence

1 per 100,000 per year.

Age

Most common 40–60 years.

Sex

M>F

Aetiology/pathophysiology

Almost all patients have the Philadelphia chromosome, a balanced reciprocal translocation between the long arms of chromosomes 9 and 22 t(9;22). This results in the c-abl proto-oncogene translocating to the bcr gene producing a novel bcr/abl fusion gene which encodes Bcr-Abl tyro-sine kinase.

CML has three phases possibly mediated by further genetic changes. Initially there is a chronic indolent phase lasting 3–5 years, followed by an accelerated phase lasting 6– to 18 months. Finally a blast crisis develops similar to an aggressive acute leukaemia.

Clinical features

Most patients with CML are asymptomatic, the disease is often found from an incidental full blood count. Patients may develop non-specific symptoms of fatigue, anorexia, weight loss, sweats and fever. On examination splenomegaly may be present.

Investigations

Full blood count and blood film reveal a high neutrophil count with a left shift (immature granulocytic forms). There may also be an increase in other granulocytes (basophils and eosinophils), thrombocytosis and anaemia. In the chronic phase blast cells account for <10% of peripheral white blood cells. The blast count rises in the accelerated phase and blast crisis.

Bone marrow aspirate shows a hypercellular marrow with an increase in myeloid precursors.

Cytogenetic studies can be used to demonstrate the Philadelphia chromosome.

Neutrophils can be stained for alkaline phosphatase, which is low in CML and high in neutrophilia caused by infection.

Management

Hydroxyurea can induce a haematologic remission and decrease splenomegaly but does not treat the underlying cytogenetic abnormality.

Interferon-α can achieve both haematologic and cytogenetic remission in up to 35% of patients but has severe flulike side effects.

Imatinib, a competitive inhibitor of the Bcr-Abl ty-rosine kinase, is recommended for Philadelphia-chromosome-positive CML in the chronic phase in adults who are intolerant of interferon-α therapy or in whom interferon-α has failed to control the disease. Cytogenetic remission is achieved in 70% of patients. It is also recommended for the treatment of adults with Philadelphia-chromosome-positive CML in accelerated phase or blast crisis provided they have not received it at an earlier stage.

Allogeneic stem-cell transplantation is used in younger patients with HLA-matched donor.