Intrabone Infusion of Cord Blood Hemopoietic Stem Cells in Adult Patients With High Risk Haematological Malignancies.
For many hematological malignancies, hemopoietic stem cell (HSC) transplant is the only
possible treatment. The source of HSC is often bone marrow (BM) or, in the past 10 years,
peripheral blood cell (PBSC) mobilized by granulocyte growth factor. Transplant needs a HLA
compatible (related or unrelated) donor. Around 10-30% of patients with indication for
allogeneic HSC transplant are not able to undergo the procedure because of the lack of a HLA
compatible donor. Cord blood (CB) cells represent another possible source, which needs a
lower degree of HLA compatibility, this type of transplant, however, offers a lower number
of HSC. For this reason, adult patients, until now, could not use this source, because of
the not suitable number of cell per kg, of recipient body weight. Recently, in experimental
animal models it was observed that intrabone HSC transplant allows, in the recipient,
engraftment of donor hemopoiesis by using a 1Log (10-1) lower number of cells compared to
the intravenous way (Yahata 2003, Castello 2004). Safety and feasibility of intrabone
infusion was verified by two clinical studies on humans: the first was conducted by Ringden
O. et al. in 18 patients without any evidence of collateral effects and with complete
engraftment of donor hemopoiesis with BM as a source of HSC (Hagglund 1998); the second one
was conducted by Frassoni et al. (Frassoni 2008) with CB as the source of HSC.
The aim of this study is to evaluate the intrabone infusion instead of the intravenous one,
for the HSC transplant from CB in patients with haematological malignancies when it is not
possible to find a HLA matched donor.
We will perform:
- evaluation of the engraftment kinetics;
- evaluation of the chimerism degree at 30, 60, 100 days, 6 months and 1 year after
- studies on immunological reconstitution and the role of the NK compartment.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Proportion of transplanted patients with successful engraftment at day +42
Within the first 42 days
Francesca Bonifazi, MD
S. Orsola-Malpighi University Hospital
Italy: The Italian Medicines Agency