This protocol is designed for a single specific patient. It uses busulfan as a conditioning
agent in a second stem cell transplant procedure for a patient with chronic granulomatous
disease (CGD), a disorder in which a certain type of white cells, called myeloid cells, do
not function properly. This causes increased risk of serious bacterial and fungal infections
that can lead to organ dysfunction, such as kidney disease, as well as formation of
granulomas-non-cancerous masses that can cause obstructions in the esophagus, stomach, and
intestines, and block urine flow from the kidneys and bladder.). The child in this study has
previously undergone a stem cell transplant to treat CGD, and, as a result, he is now
producing normal lymphocytes (another type of white cell). However, the myeloid cells from
the donor did not engraft successfully, and the patient is still producing his own defective
myeloid cells. In this study, the child will undergo a second stem cell transplant in
combination with busulfan, a drug that targets myeloid cells, killing them to make way for
healthy, donated myeloid cells.
Treatment includes the following procedures:
- Medical evaluation to confirm that the patient is healthy enough to undergo the
- Treatment with busulfan, injected through the patient's central venous line
- Stem cell transplantation through the central venous line
- Blood tests on days 25, 56, and 91 after the transplant to assess how many cells are of
- Bone marrow aspiration on day 100, and then at 12, 24, and 36 months to assess how many
cells are of donor origin
- Pulmonary function (breathing) test at 12 and 24 months
- Physical examination and blood tests, weekly or twice weekly for the first 2 to 3
months and at 4, 6, 12, 18, 24, 36, 48, and 60 months after transplant
- Treatment for graft-versus-host disease (GVHD), if this complication develops. GVHD is
the attack of lymphocytes from the donor against the patient's own cells. This is good
if it is against abnormal cells, but bad if serious damage occurs to the patient's
vital organs. GVHD is treated with steroids and cyclosporine, and possibly other drugs
This is a single patient study using intravenous busulfan as a conditioning agent for a
second allogeneic stem cell transplant in order to increase myeloid engraftment in a
previously transplanted recipient with chronic granulomatous disease (CGD).
CGD is an inherited disorder of neutrophil function leading to increased risk of infections
from both common and rare microorganisms, including fungi. Although these infections can
often be prevented or successfully treated, there are long-term sequelae including organ
dysfunction as a result of both the infections and the treatment. For example, many of the
anti-fungal agents cause renal impairment and can even lead to kidney failure requiring
dialysis. In addition, the abnormal functioning of the neutrophils leads to the development
of granulomas, which can cause obstruction of various organs, in particular within the
gastrointestinal and urogenital systems with sometimes serious sequelae. As a result the
life expectancy of patients with CGD is significantly limited with no patients documented
reaching the age of 50 and a 2 percent mortality rate per year of life.
Currently, the only available cure of CGD is bone marrow transplantation; however given its
own inherent associated morbidities and mortality, as well as the necessity for a matched
(related) donor, this has not been offered to all patients. More recently attempts to reduce
the toxicities of this potentially curative treatment have lead to the development of
non-myeloablative regimens, which as a result, can lead to partial engraftment of the donor
cells into the recipient, a situation referred to as mixed chimerism. In order to achieve an
adequate number of normal neutrophils for clinical benefit, the level of donor chimerism
needs to be at least 5 percent in the myeloid lineage. One of the patients treated on a
previous protocol with a novel nonmyeloablative conditioning regimen, has had 100 percent
engraftment of his lymphoid cells, but less than 1percent engraftment of his myeloid
lineage. As a result, he continues to experience the problems associated with CGD, but has
had no problems of graft versus host disease (GVHD). In order to improve his myeloid
engraftment, while taking advantage of the presence of his 100 percent lymphoid chimerism,
we propose to treat him with moderate dose busulfan and a purified stem cell product from
the original donor as a second transplant. With this study, the goal will be to improve this
patient's myeloid engraftment so as to ostensibly cure him of his CGD.
- RECIPIENT INCLUSION/EXCLUSION CRITERIA:
- The recipient fulfills by study design the inclusion criteria
- The patient however, would be considered ineligible for the study only If his donor
is unable to participate.
DONOR EXCLUSION CRITERIA:
- Pregnant or lactating.
- Donor unfit to receive G-CSF and undergo apheresis. (Uncontrolled hypertension,
history of congestive heart failure or unstable angina, thrombocytopenia).
- HIV positive.