Favourable Outcome of Pregnancy in Essential Thrombocythemia (ET) Patients Treated with Interferon Alpha. A Report from the Registro Italiano Trombocitemia (RIT).

Background The outcome of 129 pregnancies, in 97 women with ET diagnosed in seventeen Italian hematological centres from June 1998 to July 2007, were retrospectively analyzed by the RIT. Diagnosis was made according to criteria (PVSG or WHO) in use at the time of first observation. The median age was 27 years (range 17–45) at ET diagnosis and 32.5 years (range 21–45) at the beginning of the pregnancy. The diagnosis of ET was established in 87 patients before the first pregnancy (median interval 27 months, range 1–96), in 9 patients during a pregnancy and in one patient during an in vitro fertilization treatment. JAK2 (V617F) mutation was documented in 16 out of the 33 women studied till now. Platelet count ranged from 489 to 2,140 × 10⁹/L (median 867) at diagnosis, and from 232 to 2,000 × 10⁹/L (median 564) at delivery.

Results: Only 120 out of the 129 pregnancies are valuable (six voluntary abortions and three ongoing pregnancies are not considered).The pregnancies outcome was: live birth in 90 cases (75%), spontaneous abortion in 26 cases (22%) (19 in the first trimester and 7 in the second trimester), still-birth in 4 cases (3%). Twelve (10%) premature births were reported, and two pregnancies ending in live birth were complicated by eclampsia or pre-eclampsia. The foetal growth was within normal limits in 76 out of the 78 full term births. The delivery was by caesarean section in 40% of cases. Thirty-six pregnancies (30%) occurred during cytoreductive treatment, but the outcome was not different than in the other ET patients (p 0.49). Aspirin treatment (mainly 100 mg/ day) was reported in 92 pregnancies (76.6%), associated in 18 cases to prophylactic LMWH during the last week before delivery and six weeks post-partum. The rate of successful pregnancy in the group receiving ASA was not different respect to the group not receiving ASA (p 0.62,). JAK2 mutation was not significantly (p 0.08) associated with a higher risk of foetal loss, but the analysis has to be completed since the study is still ongoing. The IFN treatment (as single agent or combined with ASA) was performed in 21 high-risk pregnancies. Nineteen of these pregnancies were valuable (1 ongoing and 1 elective abortion): 18 pregnancies (95%) ended in live births, and this outcome was significantly better than in patients not receiving IFN (p 0.04).

Conclusion This retrospective study shows that in ET women: the IFN therapy seems able to protect against fetal loss; low-dose aspirin has not a statistically significant favourable impact on the pregnancy outcome; the unfavourable effect of JAK2 mutation could be confirmed after completion of the study. A prospective study has been recently activated by the RIT (GIMEMA project), with aim to improve the diagnostic and therapeutic approach of pregnant ET.