Reduced Intensity Conditioning for Umbilical Cord Blood Transplant in Pediatric Patients With Non-Malignant Disorders

• Determine the feasibility of attaining acceptable rates of donor cell engraftment (>25% donor cells at 180 days) following reduced intensity conditioning regimens in children < 21 years receiving cord blood transplant for non-malignant disorders. [ Time Frame: 180 days post transplant ] [ Designated as safety issue: Yes ]
  

• To describe the pace of neutrophil and platelet recovery [ Time Frame: 180 days post transplant ] [ Designated as safety issue: Yes ]
  
• To evaluate the pace of immune reconstitution. [ Time Frame: 2 years post transplant ] [ Designated as safety issue: No ]
  
• To determine the treatment related mortality, overall survival and disease free survival by days 100 and 180 post-transplant [ Time Frame: 180 days ] [ Designated as safety issue: No ]
  
• To describe incidence of acute Graft Versus Host Disease (GVHD) (II - IV) and chronic extensive GVHD [ Time Frame: 2 years post transplant ] [ Designated as safety issue: No ]
  
• To describe the incidence of grade 3-4 organ toxicity [ Time Frame: 2 years post transplant ] [ Designated as safety issue: No ]
  
• To evaluate long-term complications, such as sterility, endocrinopathy, and growth failure [ Time Frame: at least 2 years post transplant ] [ Designated as safety issue: No ]
  
• To evaluate the incidence of late graft failures at 2 years post-transplant [ Time Frame: 2 years post transplant ] [ Designated as safety issue: No ]
  

Biological: Unrelated Umbilical Cord Blood Transplant
Reduced Intensity Conditioning for unrelated umbilical cord blood transplant
Drug: Reduced Intensity Conditioning
Other Names:
• Campath
• Hydroxyurea
• Fludarabine
• Melphalan
• Thiotepa

Myeloablative doses of chemotherapy and/or radiation therapy are employed with the primary purpose of eradicating malignant cells. Additionally, these regimens exert varying degree of immunosuppression/immunoablation that aids in reducing the likelihood of rejection by host hematopoietic cells. However, myeloablative /immunoablative regimens have also been associated with significant regimen related toxicity (RRT) and regimen related mortality (RRM) that may cause death in up to 20% of patients and significantly higher rate of severe organ dysfunction or failure. While most of these RRT occur typically in the first 100 days [ e.g. VOD (veno occlusive disease), pulmonary or intracranial hemorrhage, multiorgan failure (MOF)], there are significant long term toxicities of TBI and/or chemotherapy including growth impairment, gonadal dysfunction/failure, hypothyroidism, cataracts, neurocognitive impairment, and second malignancies.

The primary objective is to determine the feasibility of attaining acceptable rates of donor cell engraftment (>25% donor chimerism at 180 days) following reduced intensity conditioning (RIC) regimens in pediatric patients < 21 years receiving cord blood transplantation for non-malignant disorders.

The secondary objectives are:

• To describe the pace of neutrophil and platelet recovery
• To evaluate the pace of immune reconstitution.
• To determine the treatment related mortality, overall survival and disease free survival by days 100 and 180 post-transplant
• To describe incidence of acute Graft Versus Host Disease (GVHD) (II - IV) and chronic extensive GVHD
• To describe the incidence of grade 3-4 organ toxicity
• To evaluate long-term complications, such as sterility, endocrinopathy, and growth failure
• To evaluate the incidence of late graft failures at 2 years post-transplant