Pregnancies in Patients with Philadelphia Negative Chronic Myeloproliferative Disorders: Interim Report of the European LeukemiaNet Data Base
Authors: Struve Sabine , Finazzi Guido , Doehner Konstanze , Schauer Stefanie , Lengfelder Eva , Gisslinger Heinz , Barbui Tiziano , Griesshammer Martin 
Published: April 2020

Abstract
Background: Philadelphia negative chronic myeloproliferative disorders (CMPDs) frequently present in women of childbearing age. Due to the high incidence of thromboembolic and hemorrhagic complications management of pregnancy is difficult in these patients. In order to document the course and outcome of pregnancies in CMPDs a registry has been implemented within the European LeukemiaNet project (work package 9). Case report forms are available via internet (http://www.uniklinik-ulm.de/struktur/kliniken/innere-medizin/klinik-fuer-innere-medizin-iii/home/studienzentrale/therapiestudien/cmps.html). A management strategy for pregnancy in CMPDs is proposed according to the experience of the authors and the available data in the literature [Griesshammer M. et al. Semin Thromb Hemost2006; 32: 422–9].
Results: From 01/2004 until 08/2008 we have registered 104 pregnancies in 52 patients including 43 patients with essential thrombocythemia (ET), 8 with polycythemia vera (PV) and 1 with primary myelofibrosis (PMF). Patients have been recruited by 7 centers from 6 countries (Austria, Czech Republic, Germany, Italy, Slovakia, Switzerland). The median age was 31,5 years (range 20,5 – 42,5 years). Seven of the 104 pregnancies are still ongoing, 8 have been terminated by elective abortion. The remaining 89 pregnancies had a life birth rate of 72% (64/89). A full-term normal delivery was observed in 86% (55/64). Spontaneous abortion was the most frequent complication occurring in 25% (22/89), mostly during the first trimester of pregnancy. Other complications such as stillbirth, premature delivery and intrauterine growth retardation occurred in 14% (12/89). The cumulative incidence of severe maternal complications was 9% (8/89), i.e. 2 cases of preeclampsia, 2 major thromboembolic events and 4 major bleeding episodes; furthermore 4 cases of microcirculatory disturbances and 2 minor bleeding episodes, i.e. recurrent epistaxis, were reported. Major thromboembolic events included a splenic vein thrombosis and a thrombotic occlusion of the vertebral artery. All major bleeding episodes were associated with obstetrical complications such as preterm detachment of the placenta, metratonia and peripartal injuries such as perineal and vaginal laceration. About half of our patients (50%) received no treatment during pregnancy, 20% had low-dose aspirin alone, 14% had low-dose aspirin plus low molecular weight heparin and the remaining patients (3%) had interferon alpha plus low-dose aspirin with or without low molecular weight heparin. In 13% information concerning treatment is still lacking. Interestingly, patients with the Jak2 mutation showed a significantly lower life birth rate compared to patients without (p = 0,0354).
Conclusions: Pregnancies in CMPDs, especially ET, go along with a live birth rate around 72%. Spontaneous abortion is the most frequent fetal complication. Maternal complications are relatively rare, nevertheless severe thromboembolic and hemorrhagic events do occur, the latter especially in context with obstetrical complications. The Jak2 mutation seems to be a significant risk factor for adverse pregnancy outcome.