Eltrombopag Plus G-CSF for Human CD34+ Cell Mobilization in Patients With Lymphoma Undergoing Autologous Stem Cell Harvest

Autologous hematopoietic stem cell transplantation (auto-HSCT) is the standard treatment for many malignant diseases, including plasma cell myeloma, lymphoma and germ-cell tumor. In the USA, it is estimated that 34,920 new cases of myeloma, 81,560 new cases of non-Hodgkin lymphoma, and 8830 new cases of Hodgkin lymphoma will be diagnosed annually.

Auto-HSCT is the first line therapy for fit patients with plasma cell myeloma and second line therapy for fit patients with relapsed/refractory lymphoma. It significantly prolongs overall survival in patients with myeloma and provides chances of cure in patients with relapsed/refractory lymphoma. The prerequisite condition to successfully perform an auto-HSCT is to mobilize and harvest an adequate amount of autologous hematopoietic stem cells. Usually, a number of 0.75-2.5 x 10^6/kg CD34+ cell is the minimal amount of hematopoietic stem cells required to safely perform an auto-HSCT. Recent study revealed increased amount of CD34+ autologous hematopoietic stem cell dose in auto-HSCT as a predictor of shortened engraftment time and better survival.

Before PBSC (peripheral blood stem cell) harvest, the hematopoietic stem cells need to be mobilized from bone marrow into the peripheral blood. In patients with malignant diseases, chemo-mobilization is the preferred mobilization method, which consists of chemotherapy 1-2 weeks prior to the harvesting procedure. Granulocyte colony-stimulating factor (G-CSF) is administered after the chemotherapy to facilitate PBSC mobilization. Following chemotherapy and G-CSF, PBSC will be mobilized into peripheral blood for harvest. The concentration of PBSC will be monitored. Once an adequate amount of PBSC is measured, a PBSC harvest procedure will be initiated. The PBSC harvest procedure usually starts 1-2 weeks following chemotherapy, and takes 1-5 days until adequate amounts of PBSC are collected. The more days a harvesting procedure takes, the larger medical risks and costs it possesses.

ESHAP is one of the most commonly used chemo-mobilization regimens in National Taiwan University Hospital. The unpublished data from National Taiwan University Hospital revealed that, it took at least 2 days to obtain adequate amount of PBSC for auto-HSCT in 40.84% of patients.

Under certain circumstances, patients may never obtain adequate amounts of PBSC for auto-HSCT even after 5 days of PBSC harvest or salvage treatment with plerixafor, a stem cell mobilizer agent. Compared to patients who obtained an adequate amount PBSC in the 1st day of stem cell harvest, these patients undertook more risks during harvest procedure and cost more medical expenditure. In addition, plerixafor is an expensive medication ($9,255 USD/each supply) that is conditional reimbursed in Taiwan. It is likely to be unaffordable for patients outside Taiwan or those without reimbursement. Without adequate amounts of harvested stem cells, the standard treatment of lymphoma (auto-HSCT) can't be performed and patient's outcome will be severely compromised. There's an urgent need to increase the percentage of patients gathering an adequate amount of PBSC on the first harvest day.