This month Ayalew Tefferi, MD, discusses managing a pregnant patient with chronic-phase (CP) chronic myeloid leukemia (CML).
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I am treating a 20-year-old pregnant woman at seven weeks gestation who was found to have CP-CML. Her white blood cell count is 300,000/µL with less than 5 percent blasts. The patient would like to keep the pregnancy and understands the risks. Leukapheresis did not provide much reduction in her counts. She remains asymptomatic with a relatively stable peripheral blood picture. Options that I have been considering include interferon now and hydroxyurea or imatinib starting in the second trimester.
Thanks to tyrosine kinase inhibitors (TKIs), most patients with CP-CML can now look forward to a near-normal life span. Obviously, no one wants to undercut this by unnecessarily deferring or discontinuing treatment with TKI. And yet, such is the challenge for this young woman who is pregnant and may also expect to breastfeed.
None of the approved TKIs for use in CML are considered safe for pregnant patients or for those intending to have children. A limited number of studies have shown relatively little effect on fertility from TKI use in prospective parents, men or women. On the other hand, their use during pregnancy is not advised because these drugs harbor off-target kinase inhibitory properties that could be harmful to fetal development and usually cross the placental barrier. Although CML itself can lead to complications during pregnancy, delaying TKI treatment in CP-CML, for a few weeks or months, has not been shown to compromise ultimate disease outcome. Therefore, it is reasonable to either simply monitor asymptomatic patients without treatment or use alternative, pregnancy-safe drugs, such as interferon, to control disease symptoms until a TKI can safely be instituted. If the situation mandates cytoreductive intervention other than interferon, I suggest therapeutic leukapheresis during the first trimester and hydroxyurea during the second or third trimester, considering the latter’s track record of safety, compared with TKIs.
- Incidental discovery of pregnancy while on TKI treatment does not necessarily mandate therapeutic abortion.
- Interferon therapy, while safe for use during pregnancy and lactation, might not be required in asymptomatic patients who can be monitored without drug intervention.
- There is no hard evidence to support specific TKI recommendations for partners.
- Although not recommended, the use of TKIs during the second or third trimester of pregnancy is not absolutely contraindicated and might be necessary in certain circumstances.
Apperley J. Issues of imatinib and pregnancy outcome. J Natl Compr Canc Netw. 2009;7:1050-8.
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NEXT MONTH'S CLINICAL DILEMMA
A 19-year-old woman had iron studies performed by her primary care physician. The results showed ferritin in the 250 ng/mL range, transferrin saturation of 38 percent, and normal liver function. Family history is remarkable for a maternal aunt with hemochromatosis, and genetic testing shows that she is homozygous for the C282Y mutation. She is gravida 0. She has no menses because of her oral contraceptive method and eats no red meat. Her most recent labs showed normal liver function; however, her iron studies showed a serum iron of 208 mg/dL, total iron-binding capacity of 268 mcg/dL, transferrin saturation of 78 percent, and ferritin 301 ng/mL. Would you start phlebotomy? And what would you use to decide on frequency of therapy? One hematologist told me to use transferrin saturation below 50 percent as a goal in premenopausal women.
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