Results of a recent study suggest that etoposide used in combination with G-CSF is a safe and effective mobilization strategy prior to stem cell transplantation in multiple myeloma patients. The combination treatment resulted in a high stem cell harvest after one day of collection in most patients.

Stem cell mobilization is the process of increasing the number hematopoietic (blood forming) stem cells in the circulating blood to ensure that enough are available to be collected for the transplant. Hematopoietic stem cells are primarily found in the bone marrow and circulate in very low concentrations in the blood. During mobilization, the administration of growth factors, such as granulocyte colony-stimulating factor (G-CSF), causes hematopoietic cells in the bone marrow to be released into the circulating blood stream.

Although G-CSF is the most commonly used mobilization agent, one recent study reported that only 34 percent of patients treated with G-CSF alone mobilized a sufficient number of stem cells for transplant over a two day collection period.

Other studies have shown that initial treatment with Revlimid (lenalidomide) has a negative impact on stem cell mobilization when G-CSF was used as a single mobilization agent.

Supplementing G-CSF with chemotherapy such as cyclophosphamide can increase the number of stem cells harvested during collection and reduce collection failure rates compared to the administration of G-CSF alone.

While cyclophosphamide is effective in improving stem cell yields, it increases the risk of low blood cell counts and high fevers associated with low white blood cell counts. In order to avoid these side effects, researchers in this study investigated the efficacy of an etoposide (VP-16) and G-CSF combination as a stem cell mobilization regimen in multiple myeloma patients.

Etoposide is a form of chemotherapy used for the treatment of lung cancer, testicular cancer, and lymphoma.  Previous studies have shown that etoposide is highly effective in mobilizing stem cells.

The 152 multiple myeloma patients enrolled in the study received 375 mg/m² of etoposide once daily on days 1 and 2 of the stem cell mobilization process. G-CSF was administered twice daily starting on day 3 until the last day of stem cell collection. Stem cells were collected from all patients between day 7 and day 13 of treatment.

Stem cells were successfully collected from all patients after one mobilization regimen.

Stem cells were harvested from 94 percent of these patients in one day of collection.  The majority of patients (61 percent) were able to undergo stem cell collection 11 days after the start of their etoposide and G-CSF regimen.

Furthermore, twice the number of stem cells were collected with G-CSF and etoposide than with G-CSF alone. These numbers were comparable to those obtained with a cyclophosphamide and G-CSF regimen.

Side effects experienced by patients in the study were manageable and were mostly the result of complications caused by low blood cell counts, which required 20 percent of patients to receive blood transfusions.  Severe fevers that required hospitalization or the administration of intravenous antibiotics occurred in 17 percent of patients.

The researchers suggested further studies be conducted to determine which compound yields the best results in combination with G-CSF in patients who are predicted to be poor stem cell mobilizers and which patients may not need a second agent for successful stem cell mobilization.

For more information, please see the study in Biology of Blood and Marrow Transplantation (abstract).