Treatment of High Risk, Inherited Lysosomal And Peroxisomal Disorders by Reduced Intensity Hematopoietic Stem Cell Transplantation
Hematopoietic stem cell transplantation has proven effective therapy for individuals with
adrenoleukodystrophy (ALD), metachromatic leukodystrophy (MLD) or globoid cell
leukodystrophy (GLD, or Krabbe disease). However, for patients with advanced or rapidly
progressive disease, the morbidity and mortality with transplantation is unacceptably high.
Unfortunately, there are no viable alternative therapeutic options for these patients; if
transplantation is not performed the patients are sent home to die. Our group at Minnesota
has developed a new protocol incorporating transplantation using a reduced intensity
conditioning regimen designed to decrease toxicity associated with the transplant procedure.
This regimen will make use of the drug clofarabine, which has lympholytic and immune
suppressive properties without the neurologic toxicity observed in the related compound,
fludarabine, commonly used for transplantation. In addition, several agents providing
anti-oxidant and anti-inflammatory properties will be used to assist in the stabilization of
the disease processes. This revised transplant protocol will test the following: 1) the
ability to achieve engraftment with the reduced intensity protocol, 2) the mortality
associated with transplant by day 100, 3) patient outcomes, based on differential
neurologic, neuropsychologic, imaging and biologic evaluations prior to transplantation and
at designated points after transplantation (day 100, 6 months, 1, 2 and 5 years).
Additional biologic studies will include pharmacokinetics of clofarabine and mycophenolate
mofetil (MMF), develop experience in kinetics of N-acetylcysteine, and evaluate biologic
markers of oxidative status during transplantation. In addition, for patients undergoing
lumbar puncture studies, cerebrospinal fluid (CSF) will be requested for determinations of
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Donor Cell Engraftment
The process of transplanted stem cells reproducing new cells.
Paul Orchard, MD
Masonic Cancer Center, University of Minnesota
United States: Institutional Review Board
|Masonic Cancer Center, University of Minnesota||Minneapolis, Minnesota 55455|