CML In Pregnancy: A Case Report Using Leukapheresis and Literature Review

Chronic myelogenous leukemia (CML) complicating pregnancy is rare and managing this specific subgroup of patients is challenging due to very limited data on this patient group. Management options differ depending on control of the CML at the time of the pregnancy. Patients who become pregnant during CML treatment with a TKI have been managed with watchful waiting, as well as Interferon-alpha, hydroxyurea, leukapheresis, and continuing tyrosine kinase inhibitors (TKI’s). Patients with concurrent diagnosis of CML and pregnancy present a more difficult management dilemma. In the absence of prospective trials, treatment has been tailored to individual patient needs and goals as well as past individual physician experience. The literature for treatment of CML in pregnancy is reviewed and a relevant case discussed.

A 37 y/o woman with past medical history five miscarriages and asymptomatic mitral valve prolapse, presented for a routine visit in her first trimester. She complained of fatigue. CBC showed white blood cell (WBC) count at 189,000 with bone marrow consistent with CML and FISH positive for BCR-ABL. Patient was offered elective abortion but declined. She was started on interferon, 90mcg per week, which was then increased to 135mcg/week after about 3 weeks. Her elevated WBC count persisted and her symptoms as well. Second opinion led to initiation of leukapheresis mid-second trimester with an empiric goal of less than 100,000. She underwent once weekly leukapheresis without significant complications and within four weeks, her white blood cell count dropped to between 50,000 and 75,000, with hemoglobin between 8.5 and 9.7 and platelets of 450,000 to 550,000 until week 32. Her fatigue improved. She had been found to have a small placental abruption at her ultrasound in the second trimester prior to leukapheresis. This led to spotting and bed rest at 32 weeks. She delivered at 35 weeks with a healthy fetus. She had a pulmonary embolus complicating her period of bed rest.

Pregnancy diagnosed concurrently with CML is uncommon and difficult to treat due to limited available options and lack of enough data about the potential harm to the fetus. Termination of pregnancy is considered safe for the mother when caught in the first trimester but was not desired in this case. Treatment during the second trimester with agents such as TKI’s is reported to be associated with fetal malformations. Interferon alpha therapy is FDA approved as category C in pregnancy, but can work slowly. Leukapheresis is thought to involve minimal risk to the fetus and minimize risk of complications of hyperleukocytosis. The effect of Leukapheresis is transient; therefore chance of rebound is high in rapidly proliferating leukemia. Successful use of leukapheresis has been reported in a few case reports.

No specific guidelines have been developed to manage this specific group of patients. Use of TKI and other cytotoxic agents may be safer in third trimester but since enough data is not available to date, use of these agents cannot be recommended as routine therapy. Use of cytotoxic agents such as hydroxyurea may also be reasonable but also are not FDA approved for use.

Leukapheresis may be a safe procedure to use in select situations when preservation of the fetus is desired, particularly during hyperleukocytosis. This procedure has very few complications and no major complications have been reported in the literature. Our patient had a PE after 2 weeks of strict bedrest in the hospital. This was not thought to be directly related to the underlying CML. The newborn was healthy at birth and the mother was treated with a TKI two weeks after delivery.