CML Treatment During Pregnancy Could Increase Risk of Congenital Malformation

September 29, 2017

Treatment with tyrosine kinase inhibitors for chronic myeloid leukemia is risky for pregnant patients, according to a new study, with the potential for congenital malformations in the baby.

Treatment with tyrosine kinase inhibitors (TKIs) for chronic myeloid leukemia (CML) is risky for pregnant patients, according to a new study, with the potential for congenital malformations in the baby.

“The prevalence of leukemia during pregnancy is approximately 1 in 10,000 pregnancies,” wrote study authors led by Mitul B. Modi, MD, MBBS, of Pennsylvania Hospital in Philadelphia, in a poster presented at the American Society for Clinical Pathology 2017 Annual Meeting, held September 6–8 in Chicago. “There is limited information on the potential effect of imatinib on the developing fetus.”

The researchers conducted a retrospective analysis from a single center in India. Of 2,008 patients with CML treated there between 1998 and 2014, there were 58 pregnant female partners of men with CML; 21 women with CML whose pregnancy ended in abortion (17 spontaneous, 4 elective); and 25 women with CML whose pregnancy proceeded to full term.

The 58 women whose partners had CML (being treated with imatinib or hydroxyurea) all had normal, full-term deliveries without any congenital malformations.

Of the women with CML whose pregnancies proceeded through the full term, all six who were treated before the imatinib era also had normal full-term deliveries without any congenital malformations.

Of the 19 remaining women who were treated during the imatinib era, 10 continued imatinib during pregnancy even after counseling, and 9 did not. All patients in both those groups were in complete cytogenetic and major molecular response (MMR) before pregnancy.

In the group of 10 women who continued therapy, there were seven normal full-term deliveries. There was one preterm delivery, and two babies were born with congenital malformations (one omphalocele, one craniosynostosis).

Of the 9 women who discontinued therapy following counseling, two patients lost MMR during the third trimester of pregnancy. There were 8 full-term normal deliveries in this group, and one patient died during the perinatal period due to sepsis. Two patients required leukapheresis.

“The management of CML during pregnancy poses a therapeutic dilemma because of the potential teratogenic effect of therapy, and requires contemplation of both maternal and fetal life,” the authors wrote. “For a patient who wants to become pregnant, we advise to plan the pregnancy carefully and try to aim for a response as deep as possible, ideally at least an MMR.” Therapy should then be interrupted, preferably with a 3-month washout period before conception and for the duration of the pregnancy. TKI therapy should then be resumed following birth.

“A more complicated issue is the unplanned pregnancy or the patient diagnosed while pregnant,” they noted. “Although there are anecdotal reports of patients who continue therapy throughout pregnancy with no problems for the baby, we do not recommend using TKI at all during pregnancy.”