Outcome and management of pregnancies in severe chronic neutropenia patients by the European Branch of the Severe Chronic Neutropenia International Registry

Zeidler, Cornelia; Grote, Ulrike; Nickel, Anna; Brand, B.; Carlsson, Göran; Cortesão, Emília; Dufour, Carlo; Duhem, Caroline; Notheis, Gundula; Papadaki, Helen Α.; Tamary, Hannah; Tjønnfjord, Geir E.; Tucci, Fábio C.; Droogenbroeck, Jan Van; Vermylen, Christiane; Voglová, J; Xicoy, Blanca; Welte, Karl

doi:10.3324/haematol.2013.099101

Cited by 31 publications

(26 citation statements)

References 27 publications

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“…G-CSF is mainly used as short-term therapy, generally requiring 4–6 days of treatment, for stem cell mobilization (Bendall and Bradstock 2014); however, it is also used as long-term treatment for patients with low-risk myelodysplastic syndrome (Jadersten et al 2005) and especially for patients with chronic neutropenia (Dale 2016; Dale and Welte 2011; Donadieu et al 2011; Zeidler et al 2014). The suggested initial doses for congenital neutropenia are 3–5 µg/kg that are increased in steps of 5 µg/kg (Dale 2016; Donadieu et al 2011), thus these G-CSF doses used in long-term therapy are also comparable to the doses used in our present study (5 µg/kg twice daily).…”

Section: Discussionmentioning

confidence: 99%

Granulocyte colony-stimulating factor alters the systemic metabolomic profile in healthy donors

2016

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IntroductionPeripheral blood stem cells mobilized by granulocyte colony-stimulating factor (G-CSF) from healthy donors are commonly used for allogeneic stem cell transplantation. The effect of G-CSF administration on global serum metabolite profiles has not been investigated before.ObjectivesThis study aims to examine the systemic metabolomic profiles prior to and following administration of G-CSF in healthy adults.MethodsBlood samples were collected from 15 healthy stem cell donors prior to and after administration of G-CSF 10 µg/kg/day for 4 days. Using a non-targeted metabolomics approach, metabolite levels in serum were determined using ultrahigh performance liquid chromatography-tandem mass spectrometry and gas chromatography/mass spectrometry.ResultsComparison of the metabolite profiles of donors before and after G-CSF treatment revealed 239 metabolites that were significantly altered. The major changes of the metabolite profiles following G-CSF administration included alteration of several fatty acids, including increased levels of several medium and long-chain fatty acids, as well as polyunsaturated fatty acids; while there were lower levels of other lipid metabolites such as phospholipids, lysolipids, sphingolipids. Furthermore, there were significantly lower levels of several amino acids and/or their metabolites, including several amino acids with known immunoregulatory functions (methionine, tryptophan, valine). Lastly, the levels of several nucleotides and nucleotide metabolites (guanosine, adenosine, inosine) were also decreased after G-CSF administration, while methylated products were increased. Some of these altered products/metabolites may potentially have angioregulatory effects whereas others may suggest altered intracellular epigenetic regulation.ConclusionOur results show that G-CSF treatment alters biochemical serum profiles, in particular amino acid, lipid and nucleotide metabolism. Additional studies are needed to further evaluate the relevance of these changes in healthy donors.Electronic supplementary materialThe online version of this article (doi:10.1007/s11306-016-1139-x) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Granulocyte colony-stimulating factor alters the systemic metabolomic profile in healthy donors

2016

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“…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.…”

Section: Pregnancymentioning

confidence: 99%

An update on the diagnosis and treatment of chronic idiopathic neutropenia

Dale¹,

Bolyard

2017

Current Opinion in Hematology

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Purpose of Review Neutropenia lasting for at least for 3 months and not attributable to drugs or a specific genetic, infectious, inflammatory, autoimmune or malignant cause is called chronic idiopathic neutropenia. (CIN) CIN and autoimmune neutropenia (AIN) are very similar and overlapping conditions. The clinical consequences depend upon the severity of neutropenia, but it is not considered a premalignant condition. Recent findings Long-term observational studies in children indicate that the disease often lasts for 3 to 5 years in children, then spontaneously remits, but it rarely remits in adult cases. The value of anti-neutrophil antibody testing in both children and adults is uncertain. Most recent data suggest that CIN and AIN are immune mediated diseases, but there are no new clinical or genetic tests to aid in diagnosis. Treatment with granulocyte colony stimulating factor (G-CSF) is effective to increase blood neutrophils in almost all cases; this treatment is reserved, however for patients with both neutropenia and evidence of recurrent fevers, inflammatory symptoms and infections. There is little or no evidence to indicate that G-CSF treatment predisposes to myeloid malignancies in this population. Summary It is important to recognize CIN and AIN, the most common causes of chronic neutropenia in both children and adults. If the neutropenia is not severe, i.e. > 0.5 × 109/L, most patients can be observed and not treated prophylactically with antibiotics or a growth factor. When neutropenia is severe treatment with G-CSF is often beneficial.

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“…We observed no events related to development of myeloid malignancies or other events in this study to indicate that G-CSF should be withheld from pregnant women. Based on the observations reported here and the wider experience of the SCNIR (19), we do not counsel neutropenic women on G-CSF against pregnancy and recommend genetic counseling for women with heritable forms of neutropenia. We also believe it is prudent to continue to long-term follow these patients and their children.…”

Section: Discussionmentioning

confidence: 96%

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

Boxer

Bolyard

Kelley

et al. 2015

Obstetrics &Amp; Gynecology

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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.

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Outcome and management of pregnancies in severe chronic neutropenia patients by the European Branch of the Severe Chronic Neutropenia International Registry

Cited by 31 publications

References 27 publications

Granulocyte colony-stimulating factor alters the systemic metabolomic profile in healthy donors

Granulocyte colony-stimulating factor alters the systemic metabolomic profile in healthy donors

An update on the diagnosis and treatment of chronic idiopathic neutropenia

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

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