Guidelines for the Management of Haematological Malignancies

PCR analysis on patients who have not achieved major molecular response after 12 months
of therapy. (Hughes, Kaeda et al. 2003)
Bone marrow should also be performed on patient who have > 2-5 fold rise, confirmed on
repeat sample (Mutation screening will also be performed)
Management of CML in Pregnancy (Fitzgerald, Rowe et al. 1986; Lipton, Derzko et al. 1996)
There is little in the way of large published series about the management of chronic myeloid leukaemia
in pregnancy. However, a number of the concerns that are associated with myeloproliferative
disorders (MPD) in pregnancy will also apply to CML.
• There is little evidence that pregnancy itself adversely affects the natural course and
prognosis of CML but any haematological disorder that may lead to hyperleucocytosis and
possibly thrombocytosis is likely to affect fertility, and may lead to an adverse outcome of the
pregnancy itself because of thrombotic or bleeding complications. This is certainly true in
primary thrombocythaemia (PT) where first trimester abortion is the most frequent
complication but increased perinatal mortality and premature delivery are also observed.
• Placental infarction due to thrombosis is the most consistent event.
• As regards management, it is desirable that some attempt to control the white cell count (and
perhaps platelet count) in pregnancy should be attempted. Hydroxyurea is teratogenic in
animals and one stillbirth and one malformed infant have been reported after exposure in
pregnancy. It should generally be avoided, but there are several well documented cases of
successful outcomes in PT with hydroxyurea given throughout pregnancy.
• Alternative treatments include α-interferon, which has been well documented as being safe in
the management of PT in pregnancy, and leucopheresis. This is the most common therapeutic
manoeuvre cited in the literature with good control of the white cell count and a successful
outcome for mother and baby in all reported cases.
Based on the published evidence, a reasonable recommendation for the management of CML in first
chronic phase diagnosed in pregnancy would be as follows:
1. Initial leucopheresis to control the white cell count, together with allopurinol and aspirin
therapy, especially if there is associated thrombocytosis.
2. Instigation of α-interferon therapy to maximum tolerated dose to control the white cell count
with intermittent leucopheresis to keep the white cell count below 20 x10 9 /l and platelets below
400 x10 9 /l until delivery.
3. No particular precautions need to be taken at delivery, assuming stable peripheral blood
parameters, and normal vaginal delivery should be possible.
The management of accelerated phase or blast crisis occurring in pregnancy is much more difficult.
• Either of these situations should warrant consideration of early termination of pregnancy and
the introduction of Imatinib therapy, but it is possible that hydroxyurea may control the
situation at least until the baby is of a great enough gestational age to deliver safely. This
policy would be associated with a relatively low risk of foetal abnormality.
• More specific therapy, including bone marrow transplantation could then be considered
following parturition.
• The potential role, if any, of Imatinib in managing CML in pregnancy is unknown at present.
Animal data does suggest that it is teratogenic in rats at doses of 100 mg/kg or more. It is
unlikely that any meaningful data will emerge regarding its use in this situation for some time.
Bone Marrow Transplantation
Bone marrow transplantation remains the only proven curable treatment for patient with chronic
myeloid leukaemia. However, the emergence of Imatinib has led to a reappraisal of the appropriate
timing of BMT.
• The excellent outcomes in young patients (