PB2223 INTERFERON THERAPY FOR PREGNANT PATIENTS WITH MYELOPROLIFERATIVE NEOPLASMS IN JAPAN

Abstract

Background:Philadelphia chromosome (Ph)‐negative myeloproliferative neoplasms (MPNs), including polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis, are clonal hematopoietic disorders characterized by the overproduction of terminally differentiated hematopoietic cells. Although PV and ET have a favorable prognosis, the incidence of thromboembolic and hemorrhagic complications is high. Thus, the goal of the current treatment strategy for patients with PV and ET is to prevent these events. MPNs mainly occur in the elderly, but can also occur in younger patients, including childbearing‐aged women. For ET in particular, there is a second peak in female patients in their thirties. In addition, the risk of miscarriage and other complications in pregnant MPN patients is higher than that in the general population; therefore, the management of MPNs during pregnancy is often discussed. The European LeukemiaNet and British Committee for Standards in Haematology have suggested interferon (IFN) therapy for MPN patients during high‐risk pregnancy. However, there are currently no guidelines in Japan.Aims:To evaluate the efficacy and safety of IFN therapy for pregnant patients with MPNs in Japan.Methods:We retrospectively analyzed eight patients with MPNs who were treated using IFN‐alpha during pregnancy at our institute. This study was approved by the ethics review board of Juntendo University Hospital.Results:One patient with PV and seven patients with ET were included. Among the ET patients, three patients harbored the JAK2 V617F mutation, whereas three patients harbored the CALR type 1 or 2 mutation. The other patient was defined as having triple‐negative ET. All ET patients had JAK2 V617F mutation, history of miscarriage, or history of platelet counts higher than 1,500 x 109/L, which is why we considered their pregnancies to be high‐risk. The dose of IFN‐alpha was from 9 million units to 21 million units per week, and the median value was 9 million units per week. Two patients started IFN before pregnancy to prepare for pregnancy, whereas six patients were treated after confirming pregnancy. All patients received low‐dose aspirin and low‐molecular‐weight heparin or heparin in the perinatal stage. The most frequent adverse event of IFN was fever, but it occurred only for the first few days. All patients continued IFN therapy until delivery. The median platelet count of the seven ET patients was 1,129 x 109/L before IFN therapy, which decreased to 336 x 109/L at the time of delivery. The hematocrit level of the patient with PV decreased from 47.0% to 40.9%, and the JAK2 V617F allele burden decreased from 87.2% to 75.4%. Two babies were born at a low birth weight, however, all of the babies’ Apgar scores were in the normal range. Neither hemorrhagic nor thromboembolic complications were reported. Significant placental infarcts were found in only one patient.Summary/Conclusion:This study represents the largest single center examination of IFN treatment for MPN patients during pregnancy in Japan, and suggests the safety and efficacy of IFN therapy for pregnant patients with MPNs. Although evidence for treatment is limited and the use of IFN for Ph‐negative MPNs is not approved in Japan, we suggest considering IFN therapy for pregnant patients with MPNs.