Successful treatment of essential thrombocythemia with alpha interferon during pregnancy

To the editor: Management of patients with hematological malignancies diagnosed during pregnancy requires consideration of the safety of the therapeutic agent(s) on the patient as well as the fetus. Chemotherapeutic agents are generally contraindicated in the first trimester of pregnancy because of the high incidence of spontaneous abortion and teratogenesis; although the incidence decreases during the second and third trimesters, agents such as hydroxyurea, commonly used in patients with myeloproliferative disorders, have an especially bad reputation throughout pregnancy (1,2). In this report we describe a pregnant woman with essential thrombocythemia, successfully treated with alpha interferon. A 36-year-old woman was found to have a persistent thrombocytosis and leukocytosis at the 6th month of pregnancy; Hb 144 g/l, WBC 22 x 109/1 and platelets 1082 x 109/l. The blood film showed basophillia and frequent giant platelets. There was no significant past personal or family history. At the time of referral she was on oral iron, folic acid and calcium. On examination the patient was 6 months pregnant and was noted to have splenomegaly 6 cm below the costal margin, firm in consistency. There were no other abnormalities. Bone marrow examination showed hypercellularity with increased myelopoietic and thrombopoietic activity with predominance of the megakaryocyte series. Cytogenetic studies were normal. Neutrophil alkaline phosphatase score was increased at 279 (NR 15 to 100). In vitro platelet function studies showed evidence of platelet hyperactivity. A diagnosis of essential thrombocythemia was made and the patient was commenced on interferon alpha 3 million units daily S.C. and aspirin 100 mg p.0. on alternate days. After 6 weeks of therapy, the spleen was palpable at 3 cm below the costal margin and the platelet count was 438 x 109/l. Because ofintrauterinegrowth retardation and a breech presentation, an elective Caesarian section was performed at 36 wk; aspirin was stopped 1 wk prior to the delivery and interferon 3 d prior to the section. A healthy male baby weighing 1870g was delivered and, apart from a rectus sheath hematoma, the perinatal course was uneventful. Two weeks post delivery the spleen had enlarged to 10 cm below the costal margin and the platelet count was 900 x 109/l. As the safety of alpha interferon in breast feeding has not been established, the patient was commenced on hydroxyurea 1 gram (20 mg/kg) on alternate days and allopurinol300 mg per d, with good results. Because of its low leukemogenic potential, hydroxyurea is now considered to be the preferred drug for patients with essential thrombocythemia and other myeloproliferative disorders (3,4). However, its potential to cause fetal malformation and intrauterine growth retardation through DNA synthesis inhibition (4, 6) precluded its use in this patient and it was considered necessary to initiate specific therapy to control the platelet count and reduce the size of the spleen prior to delivery. Alpha interferon is an effective agent in the treatment of essential thrombocythemia (4, 5) . It does not inhibit DNA synthesis and has been used successfully through the whole term of pregnancy in patients with chronic myelogenous leukemia and hairy-cell leukemia (6, 7). There have been 2 previous case reports of alpha interferon being used in the first trimester of pregnancy for essential thrombocythemia with good results and no ill effects (8, 9); in these cases, alpha interferon was stopped at around 9 wk. Our patient received alpha interferon during the second and third trimesters, with good outcome similar to those reported in patients with chronic myelogenous leukemia and hairy-cell leukemia.