Normal full‐term pregnancy in a patient with chronic myelogenous leukemia treated with α‐interferon

Management of malignancies during pregnancy represents a difficult problem because of the potential teratogenic effects of most chemotherapeutic agents. a-Interferon is an effective agent in the treatment of chronic-phase chronic myelogenous leukemia (CML) [I] and hairy cell leukemia [2]. There are no reports of pregnancy in patients receiving a-interferon (IFN-a), nor of a-IFN therapy during pregnancy. We report here a patient with chronic-phase CML who became pregnant while being treated with a-IFN, and whose leukemia was managed with a-IFN throughout her pregnancy. The patient is a 30-year-old-woman with Ph chromosome-positive CML diagnosed in February 1986. She did not have a suitable bone marrow donor for transplantation. She was treated with hydroxyurea and then with busulfan. In March 1988, she began therapy with recombinant a interferon (Roferon-A, Roche Laboratories). A dose of 4 X lo6 U/m2 subcutaneously every other day resulted in excellent control of her blood counts. Cytogenetic studies showed persistence of t(9;22)(q34;qll) in all metaphases studied. Pregnancy was documented in November 1988. The patient continued her interferon therapy. She was seen at Roswell Park Cancer Institute in January 1989. A sonogram showed a normal-appearing fetus, with an apparent gestational age of 13 weeks. The patient’s white blood cell (WBC) count was 6,900/mm3, hemoglobin 10.9 gldl, and platelet count 390,000/mm3. Therapeutic options were reviewed, and the decision was made to continue interferon therapy. The pregnancy remained uncomplicated, with normal fetal growth. The patient’s blood counts remained well controlled. In June 1989, she delivered a healthy full-term female infant, weighing 7 lb, 11 oz. The baby’s WBC count was 40,000/mm3, and she was begun on empirical antibiotic therapy. Cultures were negative, and the WBC count normalized within 48 hr. Because of the patient’s ongoing need for medication, she did not breast-feed her infant. The patient’s leukemia has remained in chronic phase on a-IFN therapy. The baby’s growth and development have been normal to date (15 months). Agents used to treat chronic-phase CML include busulfan, hydroxyurea, and a-IFN. Both busulfan and hydroxyurea inhibit DNA synthesis and may therefore cause abortion, congenital malformations, and intrauterine growth retardation. There are 23 published reports of busulfan therapy during pregnancy, with three reports of congenital malformations 131. There are no reports of hydroxyurea therapy during pregnancy. Repeated leukapheresis has been recommended by some investigators as the therapy of choice for CML during pregnancy [4]. This is cumbersome therapy, however, carrying a risk of hemodynamic instability, which may itself be detrimental to the pregnancy. The patient described here represents, to our knowledge, the first reported case of conception and successful pregnancy in a patient receiving a-IFN therapy. a-Interferon inhibits cell proliferation by effects on protein synthesis and on RNA degradation, and possibly by modulation of the immune system, rather than by inhibition of DNA synthesis 151. a-Interferon has indeed shown no mutagenecity in vitro or teratogenecity in animal studies 161. a-Interferon therapy may decrease fertility, because of decreases in serum estradiol and progesterone levels [7]. a-Interferon has abortifacient effects in rhesus monkeys, but only at doses manyfold greater than those used to treat patients 161. The case reported here demonstrates that fertility may be preserved and that pregnancy may proceed normally during a-IFN therapy. However the safety of a-IFN therapy during pregnancy will require further study before its routine use can be recommended.