Page 487 - Medicine and Surgery

P1: KOA
BLUK007-12 BLUK007-Kendall May 12, 2005 20:37 Char Count= 0

Chapter 12: Myelodysplastic and myeloproliferative disorders 483

Aetiology/pathophysiology inwhominterferon-α hasfailedtocontrolthedisease.
Almost all patients have the Philadelphia chromosome, a Cytogenetic remission is achieved in 70% of patients.
balanced reciprocal translocation between the long arms It is also recommended for the treatment of adults
ofchromosomes9and22t(9;22).Thisresultsinthec-abl with Philadelphia-chromosome-positive CML in ac-
proto-oncogene translocating to the bcr gene producing celerated phase or blast crisis provided they have not
anovel bcr/abl fusion gene which encodes Bcr-Abl tyro- received it at an earlier stage.
sine kinase. Allogeneic stem-cell transplantation is used in younger
CML has three phases possibly mediated by further patients with HLA-matched donor.
geneticchanges.Initiallythereisachronicindolentphase
lasting3–5years,followedbyanacceleratedphaselasting Polycythaemia vera
6– to 18 months. Finally a blast crisis develops similar to
an aggressive acute leukaemia. Definition
Polycythaemia vera (PV) is an overproduction of mature
Clinical features red blood cells due to a clonal proliferation in the bone
Most patients with CML are asymptomatic, the disease marrow. Myeloid precursors and megakaryocytes may
is often found from an incidental full blood count. Pa- also be increased.
tients may develop non-specific symptoms of fatigue,
anorexia, weight loss, sweats and fever. On examination Prevalence
splenomegaly may be present. 5per 1,000,000 population.

Investigations Age
Full blood count and blood film reveal a high neu- Most commonly presents over the age of 50 years.

trophil count with a left shift (immature granulocytic
forms). There may also be an increase in other gran- Sex
ulocytes (basophils and eosinophils), thrombocytosis M>F
and anaemia. In the chronic phase blast cells account
for <10% of peripheral white blood cells. The blast Aetiology
count rises in the accelerated phase and blast crisis. Idiopathicdisorder,althoughgeneticandenvironmental
Bone marrow aspirate shows a hypercellular marrow factors have been suggested.

with an increase in myeloid precursors.
Cytogenetic studies can be used to demonstrate the Pathophysiology

Philadelphia chromosome. There is clonal expansion of a pluripotent stem cell
Neutrophils can be stained for alkaline phosphatase, capable of differentiating into red blood cells, granu-

which is low in CML and high in neutrophilia caused locytes and platelets. Erythroid precursors in PV are
by infection. very sensitive to erythropoietin leading to increased red
blood cell production. Polycythemia results in increased
Management blood viscosity increasing the risk of arterial or venous
Hydroxyurea can induce a haematologic remission thrombosis. Platelet function is often disrupted risking

and decrease splenomegaly but does not treat the un- bleeding.
derlying cytogenetic abnormality.
Interferon-α can achieve both haematologic and cy- Clinical features

togenetic remission in up to 35% of patients but has Patients may be asymptomatic and the diagnosis made
severe flu-like side effects. on incidental full blood count. Patients may complain
Imatinib, a competitive inhibitor of the Bcr-Abl ty- of pruritus especially after a hot bath or shower. Hy-

rosine kinase, is recommended for Philadelphia- perviscosity may result in headache or blurred vision.
chromosome-positive CML in the chronic phase in On examination patients may appear plethoric and have
adults who are intolerant of interferon-α therapy or splenomegaly or hepatomegaly.