Here’s how readers responded to a You Make the Call question about managing a pregnant patient with chronic-phase (CP) chronic myeloid leukemia (CML).
Disclaimer: ASH does not recommend or endorse any specific tests, physicians, products, procedures, or opinions, and disclaims any representation, warranty, or guaranty as to the same. Reliance on any information provided in this article is solely at your own risk.
Despite her white blood cell (WBC) count, she still seems to be in CP-CML. The longest experience with CML in pregnancy has been with interferon alpha. It has a high molecular weight and does not cross the placental barrier and therefore is safe for the fetus. It does not increase the risk of major malformations, miscarriage, stillbirth, or preterm delivery. It is associated with significant side effects, mostly constitutional, hematologic, hepatic, and neuropsychiatric, that may interfere with the patient’s quality of life.
Hydroxyurea is better tolerated and is effective in dropping the WBC count. It is generally safe in pregnancy, but preeclampsia has been reported in association with hydroxyurea use in the second and third trimesters. Additionally, hydroxyurea rarely results in cytogenetic response.
There are not enough data to suggest that imatinib, or any tyrosine kinase inhibitor [TKI]) is safe during pregnancy, and the general consensus is not to start with that in a pregnant person. For those on it who become pregnant, it is advisable to hold or switch to interferon or hydroxyurea.
I would recommend using interferon while closely monitoring her complete blood count and leukocytes.
Zeina Al-Mansour, MD
University of Massachusetts
I suggest interferon through the entire pregnancy and then imatinib. I would switch to imatinib in the third trimester if interferon is intolerable.
Dan Zuckerman, MD
St. Luke’s Mountain States Tumor Institute
I had nearly this exact situation several years ago. The patient was on dasatinib at the time she became pregnant. We stopped dasatinib (nothing was known at the time about its safety in pregnancy, and we stopped it based on extrapolation from the data with imatinib suggesting possible fetal harm).
We used hydroxyurea to control her counts until late in the second trimester. Then, on three different occasions in the late second trimester and twice early in the third trimester, we gave cytosine arabinoside in a single dose at 1,000 mg/m2. This worked very nicely to control her WBC count. A high-risk obstetrician followed her closely with weekly ultrasounds. A healthy baby girl was delivered a few weeks early, and then the patient resumed dasatinib. Seven years later she remains on dasatinib, and the baby is now a healthy 7-year-old girl.
Tim Fenske, MD
Medical College of Wisconsin
It is rare to uncover CML during pregnancy. We have had a few cases and we suggest the use of interferon starting at a dose of 1.5 million IUand increasing it to 3 to 6 million IU for the first trimester. If the Sokal score is not high, a complete hematologic remission is quickly achieved, and if the patient tolerates interferon, you can continue this treatment until natural delivery. If you fear risk of progression, start either imatinib or nilotinib after fetal organogenesis is completed and placenta is formed (≥16 weeks). The latter does not seem to cross the placenta and has not been associated in vitro with teratogenesis, although there are fewer cases described, compared with imatinib. I would not consider hydroxyurea at any time during gestation.
You can check this review for more details and risks consideration:
Abruzzese E, Trawinska MM, de Fabritiis P, Baccarani M. Management of pregnant chronic myeloid leukemia patients. Expert Rev Hematol. 2016;9:781-91.
Elisabetta Abruzzese, MD, PhD
S. Eugenio Hospital
I think that in this case imatinib was a good choice. Busulfan or hydroxyurea are also options. None of these drugs will affect the fetus. Leukapheresis is ineffective in myeloproliferative syndromes.
Myriam E. Juárez, MD
Guatemala City, Guatemala
Kelty R. Baker, MD
If she is asymptomatic with stable counts, I would observe her until the second trimester then start interferon, with imatinib to be started at the time of delivery if the counts remain stable.
David Simpson, MD
North Shore Hospital
Auckland, New Zealand
Interferon alpha is the treatment of choice and I would continue through delivery if tolerated. If not, a low-dose TKI or hydroxyurea can be considered.
Evan D. Slater, MD
Antoine Sayegh, MD
Treat with interferon throughout pregnancy and start imatinib after childbirth.
Sabiha Gherras, MD
Tizi Ouzou, Algeria
I suggest interferon now, and then start imatinib in the second trimester.
Steven Sandler, MD
I suggest interferon alpha at CML doses until 14 weeks gestation, then switch to imatinib 400 mg daily. Consult the obstetrics team, and ensure the patient is aware of risks and benefits.
Michael Pidcock, MBBS
I would start her on interferon, then initiate imatinib during the third trimester.
Virginia Abello, MD
I would continue with interferon. If there is no response, I would discuss imatinib therapy in the second trimester with the patient.
Anil Tombak, MD