CD34+ Stem Cell Infusion to Augment Graft Function

The purpose of this study is to investigate the usefulness of infusing purified CD34+ cells
of donor origin in order to augment graft function in response to declining chimerism after
initially performing an allogeneic hematopoietic stem cell transplant (HSCT) for children
with primary immunodeficiency diseases. This protocol will be utilized for patients with
waning mixed donor chimerism that is inadequate for correction of clinical condition or
disease for which stem cell transplant was performed, or for augmentation of immune function.
An infusion of selected CD34+ stem cells will be given without any preparative regimen. As
the children eligible for this protocol have reduced immune function and pre-existing donor
chimerism, we hypothesize that stem cells will be able to engraft and the infusion will
augment graft function. This therapy serves as an alternative to a second stem cell
transplant that is known to be associated with significant morbidity and mortality. CD34+
stem cells will be collected from the donor used for initial stem cell transplant. Cells will
be T-cell depleted (TCD) by performing a CD34 selection using the CliniMACS device (Miltenyi
Biotec) in order to prevent development of new or exacerbation of existing graft versus host
disease (GVHD), as avoidance of GVHD in nonmalignant diseases is desirable. There is
sufficient data showing that mixed donor chimerism is adequate for reverting disease
phenotype in certain primary immunodeficiencies. Observations from Europe and CCHMC show that
donor chimerism might be boosted by CD34+ stem cell infusion alone without any specific
preparative regimen. This therapy is likely to be associated with low toxicity due to the
absence of a preparative regimen and lack of exposure to fresh donor cells capable of
initiating GVHD, and offers potential significant benefit.

Inclusion Criteria:

To be eligible for this protocol, patients must have the following:

1. Primary immunodeficiency (e.g. SCID, Wiskott-Aldrich and/or other more rare conditions
and other bone marrow failure syndromes) with prior allogeneic stem cell transplant.

2. Waning donor chimerism or immune function that is inadequate to correct their disease
or clinical condition, for which primary transplant was given, as determined by their
attending physician.

3. Available primary donor.

4. Must not have other organ dysfunction deemed by the attending physician to preclude
this procedure.

5. Age < 35 years at time of transplant

6. One of the following must be true:

- Patients must have evidence of persistent or recurrent immunodeficiency or
thrombocytopenia.

-OR-

• Primary immunodeficiency disease with known potential to progress to malignant condition
if untreated.

-OR-

• Debilitating secondary disease known to be a consequence of inadequate immune response to
known agent or pathogen, uncontrollable by other available medical therapies (e.g. third
patient described on page 5).

Exclusion Criteria:

1. Absence of an available original donor

2. Failure to sign consent form, or inability to undergo informed consent process

3. Pregnant or lactating female

4. Uncontrolled GVHD