Sustained G-CSF plasma levels following administration of pegfilgrastim fasten neutrophil reconstitution after high-dose chemotherapy and autologous blood stem cell transplantation in patients with multiple myeloma

Fenk, Roland; Hieronimus, Nadine; Steidl, Ulrich; Bruns, Ingmar; Graef, Thorsten; Zohren, Fabian; Ruf, Leilani; Haas, Rainer; Kobbe, Guido

doi:10.1016/j.exphem.2006.06.002

« Previous Next »Experimental Hematology
Volume 34, Issue 10 , Pages 1296-1302, October 2006

Sustained G-CSF plasma levels following administration of pegfilgrastim fasten neutrophil reconstitution after high-dose chemotherapy and autologous blood stem cell transplantation in patients with multiple myeloma

Roland Fenk
- Department of Hematology, Oncology and Clinical Immunology, Heinrich-Heine University, Duesseldorf, Germany
- Offprint requests to: Roland Fenk, M.D. Dept. of Hematology, Oncology and Clinical Immunology, Heinrich-Heine University of Duesseldorf, Moorenstr. 5, 40225 Duesseldorf, Germany
Nadine Hieronimus
- Department of Hematology, Oncology and Clinical Immunology, Heinrich-Heine University, Duesseldorf, Germany
Ulrich Steidl
- Department of Hematology, Oncology and Clinical Immunology, Heinrich-Heine University, Duesseldorf, Germany
- Harvard Institutes of Medicine, Hematology/Oncology Division, Boston, Mass., USA
Ingmar Bruns
- Department of Hematology, Oncology and Clinical Immunology, Heinrich-Heine University, Duesseldorf, Germany
Thorsten Graef
- Department of Hematology, Oncology and Clinical Immunology, Heinrich-Heine University, Duesseldorf, Germany
Fabian Zohren
- Department of Hematology, Oncology and Clinical Immunology, Heinrich-Heine University, Duesseldorf, Germany
Leilani Ruf
- Department of Hematology, Oncology and Clinical Immunology, Heinrich-Heine University, Duesseldorf, Germany
Rainer Haas
- Department of Hematology, Oncology and Clinical Immunology, Heinrich-Heine University, Duesseldorf, Germany
Guido Kobbe
- Department of Hematology, Oncology and Clinical Immunology, Heinrich-Heine University, Duesseldorf, Germany

Received 24 April 2006; received in revised form 26 May 2006; accepted 5 June 2006.

Objective

Pegfilgrastim has shown to decrease the duration of severe neutropenia after conventional chemotherapy, but its use after high-dose chemotherapy and autologous blood stem cell transplantation has not been established yet. Therefore we studied the efficacy and the pharmacokinetic profile of pegfilgrastim in patients with multiple myeloma undergoing high-dose chemotherapy.

Method

In total, 21 patients received a single subcutaneous injection of 6 mg pegfilgrastim on day +1 after transplantation and pegfilgrastim plasma levels were measured daily by enzyme-linked immunosorbent assay. Clinical outcome was compared with pegfilgrastim levels of 282 plasma samples and data of a historical control group of patients without granulocyte colony-stimulating factor (G-CSF) support.

Results

Pegfilgrastim levels showed an inverse correlation (r = −0.68, p < 0.01) with neutrophil counts. Peak levels were reached at day +4 (94 ng/mL; range: 37–205) and were maintained until day +7 (85 ng/mL; range: 35–186). Comparison with the control group without G-CSF support showed that time to neutrophil reconstitution was significantly shorter in the pegfilgrastim group with 10 vs 15 days, respectively (p < 0.001). There was no correlation of pegfilgrastim levels and the duration of neutropenia, although patients with a fivefold increase in neutrophil counts the day after pegfilgrastim administration had a significantly shorter median duration of neutropenia in comparison to patients who were less susceptible to G-CSF stimulation (5 vs 7 days, p < 0.01).

Conclusion

Neutrophil reconstitution after high-dose chemotherapy could be accelerated by the use of pegfilgrastim in patients with myeloma. Responsiveness of neutrophils to pegfilgrastim before neutropenia was correlated with faster neutrophil reconstitution, whereas G-CSF levels had no impact on neutrophil recovery.