Johannesen, Siw and Budeus, Bettina and Peters, Sebastian and Iberl, Sabine and Meyer, Anne-Louise and Kammermaier, Tina and Wirkert, Eva and Bruun, Tim-Henrik and Samara, Verena C. and Schulte-Mattler, Wilhelm and Herr, Wolfgang and Schneider, Armin and Grassinger, Jochen and Bogdahn, Ulrich (2018) Biomarker Supervised G-CSF (Filgrastim) Response in ALS Patients. FRONTIERS IN NEUROLOGY, 9: 971. ISSN 1664-2295,
Full text not available from this repository. (Request a copy)Abstract
Objective: To evaluate safety, tolerability and feasibility of long-term treatment with Granulocyte-colony stimulating factor (G-CSF), a well-known hematopoietic stem cell factor, guided by assessment of mobilized bone marrow derived stem cells and cytokines in the serum of patients with amyotrophic lateral sclerosis (ALS) treated on a named patient basis. Methods: 36 ALS patients were treated with subcutaneous injections of G-CSF on a named patient basis and in an outpatient setting. Drug was dosed by individual application schemes (mean 464 Mio IU/month, range 90-2160 Mio IU/month) over a median of 13.7 months (range from 2.7 to 73.8 months). Safety, tolerability, survival and change in ALSFRS-R were observed. Hematopoietic stem cells were monitored by flow cytometry analysis of circulating CD34(+) and CD34(+)CD38(-) cells, and peripheral cytokines were assessed by electrochemoluminescence throughout the intervention period. Analysis of immunological and hematological markers was conducted. Results: Long term and individually adapted treatment with G-CSF was well tolerated and safe. G-CSF led to a significant mobilization of hematopoietic stem cells into the peripheral blood. Higher mobilization capacity was associated with prolonged survival. Initial levels of serum cytokines, such as MDC, TNF-beta, IL-7, IL-16, and Tie-2 were significantly associated with survival. Continued application of G-CSF led to persistent alterations in serum cytokines and ongoing measurements revealed the multifaceted effects of G-CSF. Conclusions: G-CSF treatment is feasible and safe for ALS patients. It may exert its beneficial effects through neuroprotective and -regenerative activities, mobilization of hematopoietic stem cells and regulation of pro- and anti-inflammatory cytokines as well as angiogenic factors. These cytokines may serve as prognostic markers when measured at the time of diagnosis. Hematopoietic stem cell numbers and cytokine levels are altered by ongoing G-CSF application and may potentially serve as treatment biomarkers for early monitoring of G-CSF treatment efficacy in ALS in future clinical trials.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | COLONY-STIMULATING FACTOR; AMYOTROPHIC-LATERAL-SCLEROSIS; TNF-ALPHA; FUNCTIONAL RECOVERY; CEREBROSPINAL-FLUID; BONE-MARROW; SPINAL-CORD; CELLS; BLOOD; SERUM; amyotrophic lateral sclerosis; granulocyte-colony stimulating factor; cytokines; hematopoietic stem and progenitor cells; HSPC; treatment |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) Medicine > Lehrstuhl für Neurologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 09 Oct 2019 06:15 |
| Last Modified: | 09 Oct 2019 06:15 |
| URI: | https://pred.uni-regensburg.de/id/eprint/13521 |
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