Page 212 - Essential Haematology

198 / Chapter 14 Chronic myeloid leukaemia

negative remission. It is possible that imatinib, and ingly important part in providing human leucocyte
similar drugs in development, may cure some antigen (HLA) matching unrelated donors, alloge-

patients with CML but this will need much longer neic SCT can only be offered to a minority of
clinical follow - up than is available at the present patients. Relapse of CML after the transplant is a

time. significant problem but donor leucocyte infusions

are highly effective in CML (see p. 311 ), particu-
Chemotherapy larly if relapse is diagnosed early by molecular detec-
Hydroxyurea treatment can control and maintain tion of the BCR - ABL1 transcript.
the white cell count in the chronic phase but does
not reduce the percentage of BCR - ABL1 positive
Accelerated p hase d isease and b lastic

cells. A typical regimen is to start with 1.0 – 2.0 g/
t ransformation
day and then to reduce this in weekly increments
to a maintenance dosage of 0.5 – 1.5 g/day. Th e Acute transformation (20% or more blasts in the

alkylating agent busulfan is also eff ective in marrow) may occur rapidly over days or weeks (Fig.
controlling the disease but has considerable long - 14.7 ). More commonly, the patient has an acceler-

term side - effects and is now rarely used. Imatinib ated phase with anaemia, thrombocytopenia and
has now largely replaced both drugs. an increase in basophils, eosinophils or blast cells in
the blood and marrow. The spleen may be enlarged

α - Interferon despite control of the blood count and the marrow

This was often used after the white cell count had may become fi brotic. The patient may be in this
been controlled by hydroxyurea but has now been phase for several months during which the disease
superceded by imatinib. A typical regimen would is less easy to control than in the chronic phase. In
be 3 – 9 megaunits between three to seven times each both the accelerated and acute phases, new chromo-

week given as a subcutaneous injection. The aim is some abnormalities are often present. In approxi-
9

to keep the white cell count low (around 4 × 10 /L). mately one - fifth of cases, acute transformation is

Almost all patients have symptoms of a ‘ flu - like ’ lymphoblastic and patients may be treated in a

illness in the first few days of treatment which similar way to ALL with a number of patients
responds to paracetamol and gradually wears off . returning to the chronic phase for months or even
More serious complications include anorexia,
depression and cytopenias (see Table 12.1 ). A
minority (approximately 15%) of patients may
achieve long - term remission with loss of the Ph
chromosome on cytogenetic analysis although the
BCR - ABL1 fusion gene can usually still be detected
by PCR. Interferon produces an overall prolonga-
tion of the chronic phase with increased life
expectancy.
Stem c ell t ransplantation
Allogeneic SCT is a proven curative treatment for
CML but, because of the risk, is usually reserved for
imatinib failures. The results are better when it is

performed in chronic rather than acute or acceler-

ated phases. The 5 - year survival is approximately
50 – 70% although this is reduced by approximately
10% if transplantation is delayed for more than 1 Figure 14.7 Chronic myeloid leukaemia: acute

year following diagnosis. Although international myeloblastic transformation. Peripheral blood fi lm
bone marrow donor panels are playing an increas- showing frequent myeloblasts.