Hematopoietic stem cell transplantation has proven effective therapy for individuals with
adrenoleukodystrophy (ALD), metachromatic leukodystrophy (MLD) or globoid cell leukodystrophy
(GLD, or Krabbe disease). This protocol also considers other inherited metabolic diseases
such as, but not limited to, GM1 gangliosidosis, Tay Sachs disease, Sanfilippo syndrome or
Sandhoff disease, I-cell disease (mucolipidosis II).
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). In addition, for patients undergoing lumbar puncture studies,
cerebrospinal fluid (CSF) will be requested for determinations of biologic parameters.