Telomerase Activity Of CD34+ Cells - Marker For Mobilization Quality And Predictor For Engraftment After Autologous Hematopoietic Cell Transplantation
Autologous hematopoietic cell transplantation (HCT) has revolutionized the curative approach
to a number of malignancies by providing hematopoietic and immune rescue after high dose
cytoreductive therapy. In cases of residual disease, patients are usually treated with
chemotherapy to repress the disease, thereafter G-CSF injections are given serially to
encourage stem cell proliferation in the bone marrow and mobilization of the stem/progenitor
cells to the peripheral blood. Another approach, usually utilizes in myeloma patients is the
administration of G-CSF in steady state (without administration of chemotherapy) and
consequently collection of the CD34+ cells.
The minimum number of CD34+ cells threshold requires for HCT is currently defined as 2 x
10^6/kg. However, the optimal dose in terms of engraftment may be even higher (>5x10^6/kg),
especially when platelet recovery is considered.
In clinical practice, the right timing for collection is decided upon measurement of CD34, a
membrane glycoprotein of progenitors and stem-cells. CD34 levels are measured in the
expected maximal effect of the G-CSF priming, and accordingly the collection is scheduled.
Practically, if the circulating CD34+cell count is ≥20/μL, 90% of collections performed the
following day would be expected to yield ≥2.0x106 CD34+cells/kg (Gordon, BMT 1997). However,
in cases higher doses of CD34+ cells are required (e.g. for tandem HCT), CD34+ threshold may
not be sufficient to determined collection yield.
G-CSF based mobilization regimens have a 5-30% failure rate amongst patients, however in
patients with risk factors, up to 60% of the patients are failed to mobilize. Poor
mobilization has significant consequences for the patient with potential loss of
transplantation as a treatment option. Repeated attempts at mobilization increase resource
utilization, morbidity and patient inconvenience. Therefore attempts to identify patients
who would mobilize poorly are of clinical significance.
Human telomerase, a unique ribonucleoprotein complex, is inactive in normal somatic cells
but present in high levels in more than 90% of all malignancies. The enzyme, synthesize new
telomeric repeats at the 3' ends of chromosomes.
As oppose to other normal cells, stem cells are unique in that they carry active telomerase
which provides them with longer life span. Previous study from our lab showed that in
patients and healthy donors, the administration of GCSF was associated with a 14th fold
increase of telomerase activity levels in peripheral blood CD34+ cells.
Telomerase activity in mobilized stem cells is correlated with both the absolute number of
the collected cells and with the quality of the future engraftment after high dose therapy
1. To investigate the correlation between telomerase activity of CD34+ cells in the day of
collection and the total number of collected CD34+ cells in a cohort of 50 patients
undergoing stem cells mobilization and collection.
2. To explore the association between telomerase activity of CD34+ cells and the
engraftment characteristics (time to platelets>50000/microL, time to
platelets>150000/microL, time to neutrophils>500/microL, time to
3. To develop an algorithm based on CD34+ cells levels and CD34+ telomerase activity, both
measured on the day of collection, that can serve as predictor for the total number of
CD34+ cells to be collected.
Observational Model: Cohort, Time Perspective: Prospective
Ron Ram, M.D.
BMT Unit, Davidoff Cancer Center, Rabin Medical Center, Beilinson Hospital
Israel: Institutional Review Board