Use of Granulocyte Colony-Stimulating Factor During Pregnancy in Women With Chronic Neutropenia

Abstract

Objective To report outcomes associated with the administration of granulocyte colony–stimulating factor (G-CSF) to women with chronic neutropenia during pregnancy. Methods We conducted an observational study of women of child-bearing potential with congenital, cyclic, idiopathic, or autoimmune neutropenia enrolled in the Severe Chronic Neutropenia International Registry to determine outcomes of pregnancies, without and with chronic G-CSF therapy, 1999–2014. Treatment decisions were made by the patients’ personal physicians. A research nurse conducted telephone interviews of all enrolled U.S. women of child-bearing potential using a standard questionnaire. Comparisons utilized Fisher’s exact test analysis and Student’s t-test. Results One-hundred seven women reported 224 pregnancies, 124 without G-CSF therapy and 100 on chronic G-CSF therapy (median dose: 1.0 mcg/kg/day, range 0.02–8.6 mcg/kg/day). There were no significant differences in adverse events between the groups considering all pregnancies or individual mothers, e.g., spontaneous terminations (all pregnancies: no G-CSF 27/124, G-CSF 13/100; P=0.11, Fisher’s exact test,), preterm labors (all pregnancies, no G-CSF 9/124, G-CSF 2/100, P=0.12,). A study with at least 300 per group would be needed to detect a difference in these events with 80% statistical power (alpha=0.05). Four newborns of mothers with idiopathic or autoimmune neutropenia not on G-CSF (4/101) had life-threatening infections, whereas there were no similar events (0/90) in the treated group, but this difference was also not statistically significant. (p=0.124). Adverse events in the neonates were similar for the two groups. Conclusions This observational study showed no significant adverse effects of administration of G-CSF to women with severe chronic neutropenia during pregnancy.

Neonatal Alloimmune Neutropenia

“…It must be realized that NAIN, causing fulminant infections, can be a potentially fatal condition. Several case reports about severe sepsis or meningitis as a result of NAIN have been published [15,48,49,50]. As was described in the report of Lalezari et al [3], infections are not always immediately present, but often start several days after birth.…”

An update on the diagnosis and treatment of chronic idiopathic neutropenia

“…In one study of 107 women reporting on 224 pregnancies treatment with G-CSF (median dose 1.0 mcg/kg per day) in spontaneous terminations or preterm labors, and a suggestion of benefit. [35] Adverse events in the neonates were similar for the two groups. Another study analyzing 38 pregnancies, 21 in women with CIN, also showed no differences in outcomes with or without treatment for the mothers or their newborns.…”

“…[36] Transient profound neutropenia in infants born to women with CIN or AIN sometimes with severe infectious ramifications were also reported. [35, 36] Clinically this means that blood counts should be done at least a few times after birth in infants of mothers with CIN or AIN. If the neonate is severely neutropenic and there is concern about the risk of severe infections, G-CSF may be helpful in this specific setting.…”

Update on biosimilars of granulocyte colony-stimulating factor – when no news is good news

“…Clinical experience is currently restricted to postchemo/postauto-transplant neutropenia and autologous/allogeneic stem cell mobilization. Thus far, no data were reported on granulocyte mobilization for preparative apheresis [40] or on congenital and acquired neutropenias [41,42]. While several studies report financial benefits for the healthcare system, these focus on G-CSF costs and prescribing behavior.…”