Page 209 - Essential Haematology

Chapter 14 Chronic myeloid leukaemia / 195

5 Bone marrow is hypercellular with granulopoi-
etic predominance.
6 Presence of the BCR - ABL1 gene fusion by PCR
analysis and in 98% of cases Ph chromosome on
cytogenetic analysis (Fig. 14.1 d).
7 Serum uric acid is usually raised.

Treatment
Treatment of c hronic p hase
Tyrosine k inase i nhibitors
®
Imatinib (Glivec ) was designed as a specifi c inhibi-
tor of the BCR - ABL1 fusion protein and blocks
tyrosine kinase activity by competing with adenos-
ine triphosphate (ATP) binding (Fig. 14.4 ). It is the
first - line drug in the management of chronic phase

disease. At 400 mg/day it can produce a complete
haematological response in virtually all patients
(Fig. 14.5 ). Side - effects include skin rash, fl uid

retention, muscle cramps and nausea. Neutropenia
and thrombocytopenia may occur and in some
cases, dose reduction or cessation may be required.

Monitoring of r esponse to i matinib
Imatinib is highly eff ective at reducing the number
of tumour cells in the bone marrow and should be
monitored by karyotypic analysis of the bone
marrow together with PCR analysis for BCR - ABL1

Figure 14.2 Chronic myeloid leukaemia: peripheral transcripts in marrow or blood. Assessment of
blood fi lm showing a vast increase in buffy coat. The response starts with regular (3 – 6 monthly) bone
9
white cell count was 532 × 10 /L.

Figure 14.3 Chronic myeloid

leukaemia: peripheral blood fi lm
showing various stages of
granulopoiesis including
promyelocytes, myelocytes,
metamyelocytes and band and
segmented neutrophils.