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

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.