DOI: 10.25934/pr00011370
title: Analysis of whether Plerixafor can be used as a single agent for rapid collection of blood stem cells in advance of potential radiation exposure

description: In certain emergency situations, such as nuclear accidents or disasters, workers may be exposed to dangerous levels of radiation. Radiation exposure can damage the body’s ability to produce blood cells, which are essential for fighting infection, carrying oxygen, and preventing bleeding. One possible life-saving treatment is a stem cell transplant using the person’s own blood-forming (stem) cells, which can help rebuild the blood system after damage.

However, collecting and storing a person's own stem cells before entering a high-risk environment is not currently standard practice. Also, the usual method to collect these cells involves taking medication for several days, which may not be practical in urgent situations. This research project explores a faster method.

This study aims to develop a system where workers at high risk of radiation exposure can safely collect and store their own blood stem cells before they are exposed. Then, if they are harmed by radiation, their own stem cells can be used to help recover their blood system.

Specifically, we want to test whether a medication called plerixafor (a drug that moves stem cells out of the bone marrow into the bloodstream) can be safely used on its own to collect enough stem cells in a single day. In Japan, plerixafor is currently only approved when combined with another medication (called G-CSF, or granulocyte-colony stimulating factor), but we want to find out if plerixafor alone is enough. This could make the process much simpler and faster for emergency use.

If successful, this research will offer a practical, quick, and safe way for people in dangerous jobs to prepare for the worst-case scenario—radiation exposure. It could also lead to a broader emergency preparedness system for responders and improve survival and recovery after radiation incidents.

This project involves analyzing data that has already been collected from a study involving healthy adult volunteers. In the original study, participants were given a single dose of plerixafor, and then their blood was processed to collect peripheral blood stem cells (stem cells circulating in the blood). The goal is to see if enough stem cells can be collected with just one dose of the drug.

By analyzing this data, we aim to better understand whether plerixafor alone is a practical and reliable method for collecting stem cells in advance of potential radiation exposure, helping to inform future medical preparedness strategies.

[Peripheral blood stem cell collection]
Peripheral blood stem cell collection is a medical procedure in which drugs such as G-CSF and Plerixafor are used to temporarily mobilize hematopoietic stem cells that normally exist in the bone marrow into the peripheral blood, and then collect them to use as a source for hematopoietic stem cell transplantation. The specific procedure involves securing venous access in both upper limbs using an 18G or larger indwelling needle for collection, collecting blood from one side, using a collection device (Spectra Optia) to collect only the necessary components (white blood cell layer), and returning the remaining blood to the other side. The mechanism by which these drugs mobilize hematopoietic stem cells is thought to involve the temporary inhibition of the binding between SDF-1, expressed by bone marrow stromal cells, and the CXCR4 chemokine receptor, expressed by hematopoietic stem cells. This inhibition prevents hematopoietic stem cells from adhering to bone marrow stromal cells, causing them to be released into the peripheral blood. 

[Safety of prelixa]
Regarding safety, in a domestic Phase I trial (MOZ24211 trial) targeting healthy Japanese individuals, among the 18 subjects in the Plerixafor administration group (0.16 mg/kg group: n = 6, 0.24 mg/kg group: n = 6, 0.4 mg/kg group: n = 6), the following adverse events were observed: injection site local reactions (50.0%), upper respiratory tract infection (11.1%), dizziness (11.1%), diarrhea (11.1%), viral upper respiratory tract infection (5.6%), anxiety (5.6%), headache (5.6%), paresthesia (5.6%), somnolence (5.6%), palpitations (5.6%) were observed, but all were mild, and no Grade 3 or higher adverse events were observed.