ECULIZUMAB DOSE ADJUSTMENTS DURING PREGNANCIES IN PAROXYSMAL NOCTURNAL HEMOGLOBINURIA: A SINGLE CENTER EXPERIENCE.

Objective: Paroxysmal nocturnal hemoglobinuria (PNH) has always been considered a relative contraindication for pregnancy. The use of eculizumab has reduced morbidity and mortality of fetus and mother. Dose adjustments are often required due to emerging breakthrough hemolysis, no standard recommendations are currently available in this setting. Here we report our single hematology center experience on breakthrough hemolysis and eculizumab dose adjustments during PNH pregnancies. Methodology: Clinical data of four pregnancies from three PNH patients are reported. Two of them were already on standard dosage eculizumab when pregnancies were diagnosed. Their baseline PNH clone sizes were 89.5% and 97.5% on granulocytes and 38% and 90% on erythrocytes, respectively. In both cases low molecular weight heparin-prophylaxis was started when pregnancy was diagnosed. The third 26 year old patient with a baseline PNH clone of 8.8% started treatment at the beginning of her 2nd trimester. Results: The 26 year old patient was stable on 900 mg Eculizumab until 12 weeks post-partum. The other two developed breakthrough hemolysis during their third trimesters. Eculizumab dosing was increased initially from 900mg bi-weekly to 900 mg weekly and subsequently to 1200 mg biweekly. The 28 year old patient with the largest clone underwent two pregnancies and required even a 1200mg weekly dosage in her first pregnancy until four weeks post-partum. All four babies were delivered without complications. Conclusion: Eculizumab dose adjustments up to 1200 mg biweekly as well as interval shortening from bi-weekly to weekly administration seems effective and safe in breakthrough hemolysis control during pregnancy in PNH. Dose escalations did not impact on birth or development of the babies.