Protocol Number: 04-I-0289

Title:

Secondary Transplantation Using Moderate Dose Busulfan as Conditioning for a Patient with Partial Reconstitution Post Initial Allogeneic Transplantation

Number:

04-I-0289

Summary:

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% 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% in the myeloid lineage. One of the patients treated on a previous protocol with a novel nonmyeloablative conditioning regimen, has had 100% engraftment of his lymphoid cells, but less than 1% 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% 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.

Sponsoring Institute:

National Institute of Allergy and Infectious Diseases (NIAID)

Recruitment Detail

Type: Active Accrual Of New Subjects

Gender: Male & Female

Referral Letter Required: Yes

Population Exclusion(s): None

Eligibility Criteria:

ELIGIBILITY CRITERIA:

As this is a two subject study, there are no issues concerning exclusion by gender, race or age. There are also no issues concerning subject accrual.

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.

Special Instructions: Currently Not Provided

Keywords:

Chronic Granulomatous Disease

Nonmyeloablative

CD34 Positive Cells

Donor Engraftment

Myeloid Chimerism

Recruitment Keywords:

None

Conditions:

Granulomatous Disease

Chronic

Investigational Drug(s):

None

Investigational Device(s):

None

Contacts:

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citations:

Winkelstein JA, et al. Chronic granulomatous disease. Report on a national registry of 368 patients. Medicine (Baltimore). 2000 May;79(3):155-69.

Johnston RB Jr. Clinical aspects of chronic granulomatous disease. Curr Opin Hematol. 2001 Jan;8(1):17-22. Review.

Roesler J, et al. Third-generation, self-inactivating gp91(phox) lentivector corrects the oxidase defect in NOD/SCID mouse-repopulating peripheral blood-mobilized CD34+ cells from patients with X-linked chronic granulomatous disease. Blood. 2002 Dec 15;100(13):4381-90. Epub 2002 Aug 01.

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