Use of Busulfan as Conditioning Agent for a Second Stem Cell Transplant

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00092937
Recruitment Status : Completed
First Posted : September 27, 2004
Last Update Posted : July 2, 2017
Information provided by:
National Institutes of Health Clinical Center (CC)

Brief Summary:

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 transplantation
  • 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 donor origin
  • 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 if needed.

Condition or disease Intervention/treatment Phase
Granulomatous Disease Chronic Drug: Busulfan Phase 1

Detailed Description:

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 2 participants
Primary Purpose: Treatment
Official Title: Secondary Transplantation Using Moderate Dose Busulfan as Conditioning for a Patient With Partial Reconstitution Post Initial Allogeneic Transplantation
Study Start Date : September 23, 2004
Actual Primary Completion Date : April 6, 2010
Actual Study Completion Date : April 6, 2010

Resource links provided by the National Library of Medicine

Drug Information available for: Busulfan
U.S. FDA Resources

Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Senior
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
  • 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.


  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00092937

United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)

Responsible Party: Elizabeth M. Kang, M.D./National Institute of Allergy and Infectious Diseases, National Institutes of Health Identifier: NCT00092937     History of Changes
Other Study ID Numbers: 040289
First Posted: September 27, 2004    Key Record Dates
Last Update Posted: July 2, 2017
Last Verified: April 6, 2010

Keywords provided by National Institutes of Health Clinical Center (CC):
Chronic Granulomatous Disease
CD34 Positive Cells
Donor Engraftment
Myeloid Chimerism

Additional relevant MeSH terms:
Lymphoproliferative Disorders
Lymphatic Diseases
Pathologic Processes
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Alkylating
Antineoplastic Agents
Myeloablative Agonists