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was 0.25% and IFN-alpha was discontinued and imatinib elective terminations, and 14% had miscarriages. Three
was continued at 400 mg daily until January 2013. terminations occurred due to fetal anomalies. There were
In the January 2013 visit, she had conceived and had a total of 12 (9.6%) infants identifi ed to have physical
amenorrhea for 3 months. She was then informed about abnormalities, including different congenital abnormalities,
the teratogenic effects of imatinib and the possible either single or in combinations, e.g. craniosynostosis,
consequences. She elected to continue the pregnancy, so hypoplastic lungs, exomphalos, duplex or absent kidney,
imatinib was stopped in view of its teratogenic effects, hemivertebrae, shoulder anomalies, hypospadia, pyloric
and IFN-alpha 5 MU subcutaneously on alternate days stenosis, and scoliosis. One infant was born with
was restarted. The pregnancy was uneventful. She was in complex abnormalities, i.e. communicating hydrocephalus,
CHR and BCR-ABL at the second trimester was 2.14%. cerebellar hypoplasia, and cardiac defects. Cole et al.
[12]
[10]
On July 16, 2013, after 9 months of pregnancy, she showed 217 CML patients with pregnancy, of whom 78%
delivered a healthy boy with a birth weight of 2.25 kg carried their pregnancies to term, 11% had spontaneous
by caesarean section without any congenital abnormality. abortions, and 28.5% of patients with an unknown
The post-partum period was uneventful. One month outcome. Among the 109 pregnancies (78%) with known
after delivery, the patient requested that IFN therapy be outcome, 33% had complications, including spontaneous
discontinued. Imatinib 400 mg was then restarted. She abortion in 22% of patients, still birth in one patient,
was advised not to breastfeed while on imatinib. At malformations in 9 patients and low birth weight in
the last follow-up in February 2015, the patient was in 2 patients. There are limited data on pregnancy using
[12]
remission, and her baby was healthy. the second generation TKI. Cortes et al. described the
[11]
outcomes of pregnancies of 8 women who conceived while
Discussion receiving dasatinib. Three had therapeutic abortions, two
One in 1,000 pregnancies is reported with the malignant had spontaneous abortions, and three full-term delivered.
disease. [3,4] The incidence of leukemia in pregnancy is The authors concluded that women in reproductive age
one in 75,000-100,000 pregnancies. The majority of with dasatinib therapy should take effective contraception.
[5]
[13]
leukemia cases diagnosed during pregnancy are acute Conchon et al. reported a case of successful pregnancy
myeloid leukemia, followed by acute lymphoblastic and delivery in CML patient under dasatinib treatment.
leukemia. Although 15% of adult leukemia is CML, Experimental studies on nilotinib in rabbits showed
only a limited number of patients are diagnosed with treatment-associated mortality, abortion, or low gestational
[14]
childbearing age and CML accounts up to 10% of weights. However, the data on human are limited.
[15]
pregnancy-associated leukemia, with an annual incidence Conchon et al. published a case report of a successful
of one per 100,000 pregnancies. [5] pregnancy of a patient with CML on nilotinib.
Overall, malignancy during pregnancy is a unique Usually, conception during chemotherapy is not
challenge for the medical oncologist. There is another recommended; thus, couples in childbearing age must be
signifi cant problem when a patient becomes pregnant consulted to use proper contraception and inform the risk
during or shortly after receiving chemotherapy of fetal malformations for fetuses conceived while on
or radiotherapy due to the side-effects of most treatment. There are limited data regarding alternatives
chemotherapeutic agents and radiotherapy. [6-8] Side to TKI in the successful management of CML during
effects of chemo- and radiotherapy have been reported pregnancy. Most of these data were from case reports
mostly from animal studies, but there is relatively little using leukapheresis or hydroxyurea in the third trimester
information on humans. The diagnosis of CML during of gestation and low-dose IFN-alpha as maintenance
pregnancy may be made more complicated because therapy. Pegylated IFN-alpha is contraindicated in
[9]
of physiological changes in body fl uid including pregnancy due to the accumulation of polyethylene glycol.
hematological parameters. These may temporarily mask The recommended management of CML in pregnancy
the symptoms of malignancy. (as reported at American Society of Hematology 2011) is
summarized in Table 1.
For a male CML patient, there is no formal contraindication
for fathering a baby while on TKIs, and the data available A large series of the study indicated that an adequate
suggest that in most instances, babies born to such patients response after restarting imatinib only occurred in
had no known abnormalities. [9-11] Although most of the prior patients with a major molecular response (MMR)
data on the effects of imatinib on pregnancy have shown before drug discontinuation. Therefore, for women
satisfactory outcomes, they do not support a determination who choose to become pregnant despite the risk, a
that imatinib can be safely administered during the fi rst minimal MMR should be achieved to reduce a risk of
trimester of gestation. Pye et al. demonstrated the treatment failure after the reintroduction of therapy.
[16]
[10]
most comprehensive data on 180 women with CML TKI therapy should be discontinued at least 3 months
exposed to imatinib during pregnancy. Outcome data were before conception for planned pregnancy. Quantitative
available for 125 (69%) patients and of those with known reverse-transcriptase polymerase chain reaction analysis
outcomes, 50% delivered healthy babies, 28% underwent of peripheral blood at 6-weekly intervals is useful to

Journal of Cancer Metastasis and Treatment ¦ Volume 1 ¦ Issue 3 ¦ October 15, 2015 ¦ 209