Granulocyte-colony stimulating factor for hematopoietic stem cell donation from healthy female donors during pregnancy and lactation: what do we know?

Abstract

BACKGROUND Hematopoietic growth factors (HGFs) are mostly used as supportive measures to reduce infectious complications associated with neutropenia. Over the past decade, the use of HGFs became a common method for mobilizing human CD34+ stem cells, either for autologous or allogeneic transplantation. However, since their introduction the long-term safety of the procedure has become a major focus of discussion and research. Most information refers to healthy normal donors and data concerning pregnant and lactating women are scarce. The clinical question, which is the core of this review, is whether stem cell donation, preceded by administration of granulocyte-colony stimulating factor (G-CSF) for mobilization, is a safe procedure for pregnant donors. METHODS Literature searches were performed in Pubmed for English language articles published before the end of May 2012, focusing on G-CSF administration during pregnancy, lactation and hematopoietic stem cell donation. Searches included animal and human studies. RESULTS Data from animals (n = 15 studies) and women (n = 46 studies) indicate that G-CSF crosses the placenta, stimulates fetal granulopoiesis, improves neonatal survival mostly for very immature infants, promotes trophoblast growth and placental metabolism and has an anti-abortive role. Granulocyte macrophage-CSF is a key cytokine in the maternal immune tolerance towards the implanted embryo and exerts protective long-term programming effects to preimplantation embryos. The available data suggest that probably CSFs should not be administered during the time of most activeorganogenesis (first trimester), except perhaps for the first week during which implantation takes place. Provided CSF is administered during the second and third trimesters, it appears to be safe, and pregnant women receiving the CSF treatment can become hematopoietic stem cell donors. There are also risks related to the anesthesia, which is required for the bone marrow aspiration. During lactation, there should be a period of at least 3 days to allow for clearance of CSF from milk before resuming breast feeding. With regard to teratogenicity or leukaemogenity, in non-pregnant or non-lactating women reports show that CSF administration is associated with a risk for leukemia; however, this risk is not higher compared with the control population. CONCLUSIONS The information available to date indicates that administration of CSF in general, and G-CSF in particular, is safe and healthy pregnant women can serve as donors of either bone marrow or peripheral blood stem cells. However, the clinical experience is rather limited and therefore until more data become available, G-CSF should not be used during pregnancy and lactation when other therapeutic options, instead of stem cell transplantation, are available.

Cytokine patterns in nasal secretion of non-atopic patients distinguish between chronic rhinosinusitis with or without nasal polys

“…The colony-stimulating factors delay neutrophil death [ 31 ]. While G-CSF influences proliferation and differentiation of neutrophil progenitor cells as well as the function of mature neutrophils, GM-CSF often appears in the context of recruitment, activation, and survival of eosinophils [ 38 , 49 ]. Concerning G-CSF, we found levels threefold higher in NP than in controls.…”

Update on Leukemia in Pregnancy

“…Granulocyte-colony-stimulating factor (G-CSF, filgrastim) is the most commonly used colony stimulating factor. It is usually used (1) in patients with neutropenia to reduce the incidence of infectious complications, and (2) for mobilization of stem cells in donors of autologous and allogeneic HSCT [118]. The administration of G-CSF in pregnant women who serve as donors for HSCT is generally safe as data from 5 studies that included HSCT donors including pregnant females did not show any evidence of increased risk of leukemogenicity [118].…”

“…It is usually used (1) in patients with neutropenia to reduce the incidence of infectious complications, and (2) for mobilization of stem cells in donors of autologous and allogeneic HSCT [118]. The administration of G-CSF in pregnant women who serve as donors for HSCT is generally safe as data from 5 studies that included HSCT donors including pregnant females did not show any evidence of increased risk of leukemogenicity [118]. Also, data from 8 studies that included 96 pregnant females having hematological malignancies showed delivery of 94 healthy babies, but one fetal death as the mother was exposed to idarubicin and cytarabine during pregnancy in addition to one birth of a child with low intelligence and malignancy [118].…”

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

“…(2) As soon as G-CSF became available, patients and physicians began asking about the benefits and safety of its administration during pregnancy, questioning its effects on the health of both the mother and the neonate, in part because administered G-CSF crosses the placenta. (3)…”