Intrabone Infusion of Cord Blood in Adults With Hematological Malignancies
Intrabone Infusion of Cord Blood in Adults With Hematological Malignancies
The purpose of this study is to evaluate the engraftment of donor hemopoiesis (proportion of
 transplanted patients with successful engraftment at day +42) in adult patients affected by
 high risk hematological malignancies after intrabone infusion of cord blood.
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
 transplant;

 -  studies on immunological reconstitution and the role of the NK compartment.
Inclusion Criteria:

 -  Age between 18 and 65 years.

 -  Patients affected by hematological malignancies without a HLA identical sibling donor
 or unrelated donor.

 -  Informed consent.

 Exclusion Criteria:

 -  Patients with ECOG < 2.

 -  Patients with blood creatine > 2 mg/dl or with transaminase or cholestase index > 5
 times compared to normality upper limits.

 -  Patients with Cardiac Fraction Ejection < 40%.

 -  Patients with DLCO < 60% or Diffusing Lung Capacity of carbon monoxide attesting a
 severe pulmonary insufficiency.

 -  Patients with peripheral blast cell count over 10%.

 -  Second neoplasia diagnosed no more than 2 years before.

 -  Patients with active or suspected infection by fungi for which a therapeutic treatment
 is ongoing.

 -  HIV positive patients.

 -  HCV-RNA and HBV-RNA positive patients (it is possible to enrol them after discussion
 with the Principal Investigator).

 -  Pregnant or lactating women.

 -  Severe mental diseases.