Sickle cell disease is an orphan disease and patients with high-risk features, including those with a history of cerebral vasculopathy and/or pulmonary and/or pulmonary vascular complications portend to have a poor prognosis with a high tendency toward serious chronic morbidities and premature death. The only curative and organ stabilizing therapy is allogeneic stem cell transplantation (AlloSCT) from unaffected human leukocyte antigen (HLA) matched sibling donors. However, only approximately 15% of SCD patients have such donors. An alternate allogeneic donor source includes unaffected FHI donors. The use of this donor source is limited by increased risks of graft-versus-host disease (GVHD) and/or graft failure. However, these risks can be minimized by the use of T cell depletion (TCD) through positive selection of CD34+ hematopoietic stem cells followed by minimal T cell addback. FHI TCD AlloSCT utilizing CD34+ hematopoietic stem cell positive selection has been demonstrated to be successful in patients with high-risk hematological malignancies. Currently there is no FDA indication for this device/procedure for non-malignant diseases, such as SCD. The specific objectives include: 1) to determine safety and feasibility of host myeloimmunosuppressive conditioning (MIC) followed by FHI TCD AlloSCT in high-risk patients with SCD;2) sustained donor whole blood and red blood cell chimerism;3) quality and quantity of immune cell reconstitution and function;4) changes in neurological and neurocognitive sequelae;5) differences in pulmonary and pulmonary vascular function;and 6) changes in health-related quality of life (HRQL).

Public Health Relevance

Sickle cell disease (SCD) affects approximately 80,000 patients in the U.S. (an orphan disease) in which, high- risk populations have been identified that portend a high-risk for serious chronic morbidity and early mortality. The only curative therapy at the present time is allogeneic stem cell transplantation from unaffected tissue matched family donors. The proposed research will determine the safety and feasibility of utilizing an experimental cell depletion procedure in non-tissue matched unaffected family donors as an alternate donor source for allogeneic stem cell transplantation with the intent of disease and organ stabilization, improvement in quality of life, long-term cure and FDA approval of this experimental device/procedure for this orphan disease (SCD).

Agency
National Institute of Health (NIH)
Institute
Food and Drug Administration (FDA)
Type
Research Project (R01)
Project #
1R01FD004090-01A1
Application #
8354332
Study Section
Special Emphasis Panel (ZFD1-OPD-N (S1))
Project Start
2012-04-16
Project End
2016-03-31
Budget Start
2012-04-16
Budget End
2013-03-31
Support Year
1
Fiscal Year
2012
Total Cost
Indirect Cost
Name
New York Medical College
Department
Pediatrics
Type
Schools of Medicine
DUNS #
041907486
City
Valhalla
State
NY
Country
United States
Zip Code
10595