Dear Editor,
Granulocyte colony stimulating factor (GCSF) has been safely used for PBSC mobilization for more than two decades [1]. However, data on GCSF induced PBSC harvesting from pregnant healthy women and its effects on the fetus and the recipient is scarce. Here, we report the effects of GCSF induced PBSC harvesting in the second trimester to the donor, her fetus and recipient.
A 27 years old male, diagnosed with severe aplastic anaemia, pending his HLA matching, was started on cyclosporine and danazol therapy. In view of unresponsiveness to cyclosporine therapy, younger age and a past history of life threatening fungal infection, he was planned for an allogeneic hematopoietic stem cell transplant (HSCT). He had a 10/10 sibling match with his younger sister (25 years); however, she was pregnant, in her second trimester of pregnancy (21 weeks of gestation) without any co-morbidity. After a detailed discussion of therapeutic options for the patient (horse ATG—antithymocyte globulin) and possible risks to the donor and fetus, she consented for GCSF induced allogeneic PBSC donation. She was mobilized using GCSF s.c. (10 mcg/kg/day in two divided doses) for 4 days. In view of a suboptimal CD34 collection on fifth-day (0.3 × 106/kg), a second harvest was done on subsequent day. Total CD34 dose collected was 2.14 × 106/kg (final volume: 606 ml). The donor tolerated the procedure well. Pre-and post-apheresis, she was monitored with an ultrasound doppler every 2 weeks indicating normal fetal activity and development. At 41 weeks, she delivered a normal healthy male child with birth weight 3 kg and normal leukocyte counts. Currently, after 21 months of GCSF administration, her child has achieved all developmental milestones as per age and donor is healthy and asymptomatic.
The patient had neutrophil engraftment on day + 11 posts Flu-Cy-ATG conditioning. At day + 30, patient had complete donor chimerism. On day + 49, he developed steroid responsive grade 3 gut and skin GVHD. On his last follow-up at day + 620, he is disease free with manageable moderate stage chronic skin GVHD.
Our report illustrates a viable healthy fetal outcome without any hematological alterations and a disease free recipient after duration of 21 months. Although GCSF has been used in pregnancy for patients with congenital/cyclic neutropenia, and to stimulate neonatal granulopoiesis in critically ill premature neonates, data for its use in PBSC mobilization is scarce (Table 1). Pessach et al. have mentioned, that CSFs are safe when administered in second and third trimester, and should not be used in first trimester [period of organogenesis]. However, it has been used as a treatment for unexplained primary miscarriages, possibly due to a direct trophic effect on trophoblasts, inferring that it may be used in first trimester, only during the first week of implantation. Even bone marrow harvest in pregnancy can be done, provided it is done under spinal/epidural anaesthesia [risk of aspiration with General anaesthesia], adequate hydration with minimal harvest volume, and delayed until 28 weeks for better neonatal outcome, in case of an uneventful premature delivery [4]. Similarly, during lactation, GCSF can be given, as long as breast feeding is resumed after a period of 72 h. In terms of safety, there is no convincing data of increased spontaneous abortions, embryonic or fetal malformations and no increased incidence for long term teratogenicity/leukaemogenity, as compared to control population [1]. However, the effect of a PBSC graft mobilized from a pregnant donor on engraftment and GVHD rates, remains unanswered.
Table 1.
Studies reported for use of GCSF for stem cell mobilization in pregnancy
| Characteristics/study | Leitner et al. [2] | Debus et al. [1] | Neidemener et al. [3] | Our case |
|---|---|---|---|---|
| Pregnancy duration (weeks) at time of exposure to GCSF | 8 | Peri-implantation | 29 | 21 |
| Trimester | First | First | Third | Second |
| Allogeneic/autologous | Allogeneic (NHL) | Allogeneic (AML) | Autologous (AML) | Allogeneic (SAA) |
| Weeks of gestation | 40 | 38 | 37 | 41 |
| Days of GCSF | 4 | 4 | 6 | 5 |
| CD34 dose (× 106/kg) | 2.05 | 6.4 | 19.8 | 2.14 |
| Birth weight (kg) | 3.4 | 2.95 | 1.7 | 3 |
To conclude, pregnancy is a contra-indication to stem cell donation. However, if the recipient’s situation necessitates urgent allogeneic HSCT and if any alternative donor is not available, then after an informed consent a pregnant woman in second trimester may be considered as a potential donor for PBSC apheresis.
Acknowledgements
We thank all the members, and staff of Rajiv Gandhi Cancer Institute and Research Centre, India for their contribution in the conduct of the study.
Funding
Funding information is not applicable to this study.
Compliance with Ethical Standards
Conflict of interest
All authors declare that they have no conflict of interest.
Ethical Approval
This study is a case report and does not explore any research question. The approval from the IRB of our institute has been received for the publication purpose.
Informed Consent
The informed consent was obtained from the individual recipient and donor for using their information for publication.
Footnotes
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References
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