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.

Sex

All

Minimum age

36 Months

Maximum age

60 Years

Inclusion Criteria:

1. Age 36 months to 60 years old (YO)
2. No prior autologous or allogeneic transplant
3. Karnofsky performance score or Lansky Play-Performance of at least 80

Exclusion Criteria:

1. Age \< 36 months or \> 60 YO
2. creatinine clearance or nuclear medicine GFR of \< 50 mL/min
3. cardiac ejection fraction \< 50%
4. bilirubin \> 2 × upper limit of normal or ALT \> 4 × upper limit of normal or unresolved veno-occlusive disease
5. Pulmonary carbon monoxide diffusing capacity (DLCO), adjusted for Hgb \< 50%
6. Karnofsky performance score or Lansky Play-Performance Scale \<80
7. Uncontrolled viral, bacterial, or fungal infection at the time of study enrollment
8. Seropositive for HIV
9. Availability of a willing and well HLA matched related (genotypically identical or mismatched at a single allele or antigen defined by typing at HLA A, B, C and DRB1 loci) donor
10. Availability of a willing and well HLA matched unrelated (allele matched or mismatched at a single allele defined by allele level typing for HLA A, B, C and DRB1 loci) adult blood or marrow donor
11. Availability of an umbilical cord blood unit, which provides at least a 4/6 HLA match as defined above and ≥ 5.0 \* 107 NC/Kg (cryopreserved)