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Cytokines alone for PBPC collection in patients with advanced gynaecological malignancies: G-CSF vs G-CSF plus EPO

Bone Marrow Transplantation volume 34, pages 743–744 (2004)Cite this article

Over the last 15 years we have observed a continuously increased clinical use of autologous PBPC transplantation capable of rapidly restoring haematopoiesis after drug dose-intensification treatments in patients with high-risk malignancies.1, 2 The PBPC dose administered determines in part the success of the engraftment,3 thus making an effective PBPC mobilization a critical step for the entire procedure. Owing to the very low number of CD34+ cells in the peripheral blood under steady-state conditions, several mobilization strategies based on the use of either chemotherapy or haematopoietic growth factors or a combination of both have been developed to increase the number of PBPC beyond the steady-state level.4 Recently, two EPO-based cytokine regimens have been proposed by our group for PBPC mobilization in patients with advanced ovarian cancer by using a disease-oriented chemotherapy supported by G-CSF or sequential GM-/G-CSF in combination with EPO, demonstrating that EPO significantly increases all the well-known myeloid growth factor properties in patients recovering from drug-induced myelosuppression.5, 6 However, whether mobilization with chemotherapy plus cytokines should be preferred over cytokines alone represents a clinically relevant aspect that remains to be established in the autologous setting. Data from clinical trials suggest that the greatest progenitor mobilization is obtained with chemotherapy followed by the administration of growth factors, but this approach is likely to cause additional toxicities and costs for patients' care.7, 8, 9 At present, G-CSF alone represents the gold standard for mobilization of PBPC from healthy donors for allogeneic transplantation, but only a few studies have used G-CSF alone to mobilize autologous PBPC in breast cancer patients,9, 10 while no data are available for gynaecological malignancies. In this context, the PBPC yield collected by growth factor alone could be potentially increased by using a combination of cytokines. To address this issue, 25 patients with advanced gynaecological malignancies (13 patients with histologically confirmed stage IIIC–IV ovarian carcinoma and 12 patients with stage IIB–IVA cervical cancer) were enrolled in our institution into a prospective nonrandomized study investigating the role of the G-CSF plus EPO combination for PBPC mobilization in steady-state conditions. All patients had not been previously treated with chemo/radiotherapy and were comparable with respect to age (median age 51 and 46 years for ovarian and cervical cancer patients, respectively) and haematological characteristics. In all, 10 patients (G-CSF group) received recombinant human G-CSF 10 μg/kg/day subcutaneously from days −4 to −1, while 15 patients underwent different EPO-based mobilization regimens (G-CSF+EPO group). In particular, five patients received G-CSF 5 μg/kg/day plus concomitant EPO 150 IU/kg/day subcutaneously from days −4 to −1, five patients received G-CSF 10 μg/kg/day plus concomitant EPO 150 IU/kg/day from days −3 to −1, and five patients received G-CSF 10 μg/kg/day plus concomitant EPO 150 IU/kg/day from days −4 to −1. Leukapheresis procedures were started on day 0 with the aim of collecting a single or multiple dose of 1.5 × 106 per kg CD34+ cells to support a single or multiple cycles of high-dose nonmyeloablative disease-oriented chemotherapy in an outpatient setting. As shown in Table 1, no statistically significant differences in CD34+ cell count per μl were observed in our patient series, the median count of CD34+ cells being 66.5/μl in the G-CSF alone group and 49.2/μl in the G-CSF+EPO group. The median number of leukapheresis procedures to obtain the planned dose of CD34+ cells was comparable in the two groups. Consequently, the number of PBPC collected per kg by aphaeresis was similar, the median count of CD34+ cells being 3.2 and 2.4 × 106 per kg in the G-CSF alone group and in the G-CSF+EPO group, respectively. No significant differences were observed in the number of total nucleated cells and PBMC collected per kg by aphaeresis (Table 1). Moreover, no statistically significant difference was observed in PBPC mobilization and collection efficiency when considering the comparison among the G-CSF alone group and the different EPO-based subgroups (data not shown). Side effects in patients receiving any type of cytokine regimen were mild and most symptoms were relieved by common nonsteroidal analgesics. Limited data are available with regard to PBPC mobilization/collection with cytokines alone in patients with solid tumours. Our experience in patients with advanced gynaecological cancer confirms that G-CSF priming is feasible and achieves CD34+ cell yields comparable to those reported in breast cancer.9, 10 Moreover, in our series EPO addition to G-CSF in different schedules does not seem to improve PBPC mobilization/collection, suggesting that potentiation of PBPC mobilization induced by EPO in chemotherapy primed patients5, 6 cannot be reproduced in steady-state conditions. Therefore, G-CSF alone remains the most cost-effective cytokine regimen to promote PBPC recirculation in cancer patients in steady-state conditions. These findings will contribute to the future planning of optimal cytokine combination strategies for PBPC collection in cancer patients.

Table 1 Mobilization and collection of PBPC by leukapheresis
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Authors and Affiliations

  1. Gynaecologic Oncology Unit, Catholic University of the Sacred Heart, Rome, Italy

    A Perillo, G Ferrandina, S Mancuso & G Scambia

  2. Immunohaematology and Transfusion Service, ASL Viterbo, Viterbo, Italy

    L Pierelli

  3. Department of Haematology and Blood Transfusion, Catholic University of the Sacred Heart, Rome, Italy

    S Rutella

  4. Cord Blood Stem Cell Project ‘Fondazione Cassa di Risparmio’, Rome, Italy

    A Perillo, S Rutella, S Mancuso & G Scambia

  5. Department of Oncology, Catholic University of the Sacred Heart, Campobasso, Italy

    G Scambia

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Perillo, A., Ferrandina, G., Pierelli, L. et al. Cytokines alone for PBPC collection in patients with advanced gynaecological malignancies: G-CSF vs G-CSF plus EPO. Bone Marrow Transplant 34, 743–744 (2004). https://doi.org/10.1038/sj.bmt.1704584

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