Impact of G-CSF on Outcomes of Pregnancy in Women with Severe Chronic Neutropenia
Authors: Boxer Laurence A. , Bolyard Audrey Anna , Marrero Tracy M. , Phan Lan , Bond Jordan M. , Alter Blanche P , Bonilla Mary Ann , Link Daniel , Newburger Peter E. , Rosenberg Philip S. , Shimamura Akiko , Dale David C. 
Published: October 2019

Abstract
Abstract 4786
Pregnancy in patients with severe chronic neutropenia is associated with high risk of spontaneous abortions. Patients and physicians often ask about benefits and safety of G-CSF administration during pregnancy. We therefore conducted a telephone survey of women of child-bearing potential with the diagnoses of congenital, cyclic, idiopathic or autoimmune neutropenia who are enrolled in the North American branch of the Severe Chronic Neutropenia International Registry (SCNIR).
We identified 99 women who had 214 pregnancies before and on G-CSF for this cross sectional study, expanding our previous preliminary investigation, (Boxer et al, ASH abstract 2010). In this population, 31 women had pregnancies before availability of G-CSF, 35 were on long term G-CSF at the time of their pregnancies and 33 were taking G-CSF for some, but not all, of their pregnancies. For those on G-CSF during their pregnancies, the median G-CSF dose was 1.30 mcg/kg/day (mean dose 2.2 ± 0.4 [SEM] mcg/kg/day, dose range 0.1 to 28 mcg/kg/day). Treatment was administered throughout the pregnancy in 74% (49/65) of the pregnancies. Five percent (3/65) were treated only in the 1st trimester, 11% (7/65) were treated only in the last 2 trimesters, 5% (3/65) treated for the last trimester only, and 5% (3/65) treated in 2 of 3 trimesters (2 treated in 1st and 3rd trimesters, 1 treated in the 1st and 2nd trimesters). Sixty-two women with 137 pregnancies while not on G-CSF [congenital neutropenia (CN) N=3, cyclic neutropenia (CyN) N=15, idiopathic neutropenia (IN) N=43, autoimmune neutropenia (AN) N=1] were compared with 47 women having 77 pregnancies while on G-CSF therapy [CN=9, CyN=14, IN=21, AN=3].
Pregnancies occurring in neutropenic women without G-CSF therapy had the following complications: premature labors (8), premature rupture of membranes (1), life-threatening infections (2), and minor infections (5). Patients on G-CSF during pregnancy reported no premature labors (0), no life threatening infections (0), minor infections (5), thrombocytopenia (1), placenta previa (1), abruptio placenta (1), and death following incomplete elective termination (1). By diagnostic category complications in the no G-CSF mothers occurred in 16 patients (CN=1, CyN=5, IN=9, AN=1), compared with nine in the G-CSF treated group (CN=1, CyN=4, IN=4). There were 31 spontaneous miscarriages in the women not on G-CSF (CyN=8, and IN=23) compared with 5 in the women (CyN=4, IN=1) on G-CSF.
There were 93 live births from 137 pregnancies in the non G-CSF group. Thirteen of these infants had neonatal neutropenia. Other major neonatal complications in the no G-CSF group included significant infections (3) [meningitis 1, septicemias 2], minor infection (1), cerebral palsy associated with prematurity (1), respiratory distress syndrome (1), and collapsed lung (1). In the G-CSF treated group there were 65 live births from 77 pregnancies. Fifteen of these infants were neutropenic. Other complications in the G-CSF treated group included minor infections (2), abruptio placenta associated with neonatal apnea (1), and premature infants with associated complications (2). There were 2 congenital abnormalities: tracheal esophageal fistula (1) and hydronephrosis (1) in 65 live births, a frequency similar to the general population.
This study showed that women with chronic neutropenia who were on G-CSF during pregnancy had a higher percentage of live births, 84% (65/77) than those not on G-CSF, 68% (93/137) (p=0.011, two tailed Fisher exact test). G-CSF therapy was associated with a lower number of spontaneous abortions, with a 6% (5/77) spontaneous abortion rate in the G-CSF treated group versus 23% (31/137) in the non G-CSF group (p=0.003, two tailed Fisher exact test). G-CSF therapy was also associated with a lower rate of serious maternal complications. Two common congenital anomalies (2/65) were observed in the offspring of the G-CSF treated mothers and no anomalies were observed in the offspring of the mothers not receiving G-CSF. Overall the newborns from the G-CSF treated mothers appeared to have fewer neonatal complications. Based on this analysis, we recommend that G-CSF therapy should be offered and continued during pregnancy in women with severe chronic neutropenia. The available data indicates that administration throughout pregnancy is well tolerated and protective of maternal health, including reducing the risk of infections and spontaneous abortions.

Disclosures:
Boxer: Amgen: Equity Ownership. Dale:Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.