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The increased use of granulocyte colony-stimulating factor (G-CSF) – mobilized peripheral blood stem cells (PBSCs) for allogeneic transplantation has led to guidelines for donor evaluation procedures to protect the safety of the PBSC donor (Joint Accreditation Committee of International Society for Haematotherapy and Graft Engineering (ISHAGE)-Europe and European Group For Blood and Marrow Transplantation (EBMT), 2000). Pregnancy is a contraindication for G-CSF-induced allogeneic PBSC donation, although current information is insufficient to establish definitive exclusion criteria. Here we report an allogeneic donor with unrecognized early pregnancy at the time she underwent G-CSF induced PBSC donation.

A 29 year-old woman was selected for G-CSF-induced allogeneic PBSC donation for her 23 year-old brother suffering from non-Hodgkin's lymphoma. After informed consent was obtained, 3 weeks before PBSC donation she underwent a standardized medical examination including a detailed questionnaire regarding the possibility of a pregnancy. The donor denied any pregnancy and the physical examination and all laboratory tests were normal. For PBSC mobilization, she received a 4 day course of recombinant human G-CSF subcutaneously at a dose of 10 µg/kg body weight (b.w.)/d (Filgrastim; Amgen, Thousand Oaks, USA). PBSC donation was initiated on d +5 via peripheral vein access. She tolerated PBSC apheresis without remarkable events and, after two aphereses, 2·05 × 106 CD34+ cells/kg recipients' b.w. (110 kg) were collected. After completion of stem cell apheresis, the donor was included in our institutional PBSC donor follow-up programme. At a control examination 3 months after PBSC donation she reported her pregnancy. The gynaecological examination revealed a singleton intrauterine pregnancy; gestation was calculated to have occurred 8 weeks before the start of G-CSF administration. Repeat ultrasound scans throughout pregnancy showed no malformations or intrauterine abnormalities in fetal development. Pregnancy progressed uneventfully and, after 40 weeks of gestation, the donor delivered a male baby at term. APGAR index at birth was 9, 10, 10; birth weight (3·42 kg) and birth length (50 cm) were within the normal percentile. Parturition and post-natal growth was unremarkable. Repeat paediatric examinations until the age of 18 months showed no evidence of haematological or immunological alterations.

Our report illustrates that in females scheduled for G-CSF-induced allogeneic PBSC donation an early pregnancy may be unrecognized, despite a careful medical examination. Considerations against the administration of G-CSF during pregnancy include an unknown risk of spontaneous abortion or the risk of embryonic or fetal malformations (Boxer et al, 1995), as well as concerns about potential long-term effects such as teratogenicity or leukaemogenity. In our donor, however, pregnancy resulted in the successful delivery of a healthy baby, which is in agreement with other case reports demonstrating no serious effect of G-CSF administration on fetal development (Fujiwaki et al, 1995; Kaufmann et al, 1998; Abe et al, 2000; Cavallaro et al, 2000). The data from these few patients, however, are inconclusive to assess the safety of G-CSF administration on gestation. Therefore, we recommend that a pregnancy test should be included in the evaluation procedure for female PBSC donors of child-bearing age as well as obtaining detailed donor information. It should be considered that informed consent from the donor is required for the pregnancy test. Ideally, after consent has been obtained, the pregnancy test should be performed on the days before the recipient's high-dose therapy has begun. Using this approach, we believe that the uncertain risks of G-CSF administration on gestation can be reduced.

References

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