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 The unpublished data from National Taiwan University Hospital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.
Eltrombopag is a thrombopoietin (TPO) receptor agonist that has been approved by the
United States Food and Drug Administration for the treatment of immune thrombocytopenia
(2007) and aplastic anemia (2014). It has been proven that TPO agonists can stimulate
stem cell proliferation and maintenance. One study showed administration of eltrombopag
increased the stem cell amount harvested from patients with plasma cell myeloma.
Investigators hypothesized that addition of eltrombopag during ESHAP PBSC mobilization
will increase the amount of harvested stem cells in patients with lymphoma.
In addition, a study in patients with aplastic anemia showed positive correlation of
serum eltrombopag concentration with treatment efficacy. A higher peak serum eltrombopag
concentration were associated with higher response rate. This raises the interest of
measuring serum eltrombopag in this study. The association of serum eltrombopag
concentration and harvested PBSC amount will be explored as well.
In conclusion, this study aimed to explore the activity of eltrombopag in ESHAP PBSC
mobilization. Participants will receive eltrombopag following ESHAP chemo-mobilization.
The amount of PBSC, and its association with peak serum eltrombopag will be measured.