Intraosseous Infusion of Unrelated Cord Blood Grafts

In this trial the investigators seek to determine if injecting cord blood cells directly
into the bone marrow (intraosseous injection), rather than infusing them intravenously, can
improve engraftment. The rational for doing this is that most hematopoietic stem cells
(HSCs) infused intravenously never reach the bone marrow, getting trapped by other organs,
such as the lungs, instead. The potential advantage of intraosseous infusion is suggested
by studies in rodents that have demonstrated that in HSC transplants where the cell dose is
limiting intraosseous injection is a more effective route of administration. The safety of
intraosseous injections, in general, is underscored by the vast experience using
intraosseous injections for resuscitation of critically ill children. The safety of
injecting HSCs intraosseously has been demonstrated in a clinical trial of transplanting
bone marrow cells.

To safeguard against problems that might result, if intraosseous infusion fails to improve
engraftment in this trial, the investigators will integrate a recently introduced strategy
proven to improve engraftment-the transplantation of two cord blood units. Transplanting
two unrelated cord blood units by intravenous infusion has been shown to improve engraftment
(although there is still room for improvement). In this trial one unit will be injected
intraosseously and the other unit will be infused intravenously.

This study is being conducted as a forerunner to a larger, multi-center trial. The
investigators intend to enroll five patients over 1-2 years.