Conditions: Osteopetrosis
Keywords: osteopetrosis
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 3
Healthy volunteers: no

Brief summary:
We believe that hematopoietic stem cell transplantation (HSCT) will help subjects with Osteopetrosis generate functioning osteoclasts, and by so doing assist in the resolution of the abnormal bone architecture, and the anemia and bone marrow failure that is also characteristic of this disease. However, we have found in past studies that approximately 30% of Osteopetrosis patients do not engraft. Therefore, in this study, we plan to use a different combination of pre-transplant drugs to try to make transplants safer for this disease, as well as to provide a second infusion of stem cells in patients with matched related or unrelated donors. The purpose of this research is to find a safer and more effective means of performing stem cell transplantation in patients with Osteopetrosis, using chemotherapy and radiation designed to bring about engraftment and lessen transplant mortality.

Detailed description:
This transplant protocol will test the following: 1) the ability to achieve engraftment with the reduced intensity protocol, 2) the mortality associated with transplant by day 100, 3) patient outcomes, based on differential imaging and biologic evaluations prior to transplantation and at designated points after transplantation (day 100, 6 months, 1, 2 and 5 years). Additional biologic studies will include microarray analysis, Campath levels just prior to the administration of the graft, and establishment of mesenchymal stem cell lines. In older patients, studies to evaluation osteoclast differentiation and function will also be offered.

Arms:
arm 1: Patients enrolled and received study treatment.

Interventions: intervention 1: Stem Cell or Umbilical Cord Blood Transplantation intervention 2: Campath, Busulfan, Clofarabine intervention 3: Total Lymphoid Irradiation
Intervention descriptions: intervention 1: Stem Cell (unrelated or matched related donor grafts (both peripheral blood and marrow) infusion on Day 0 and 42; Umbilical Cord Blood on Day 0 and 42 intervention 2: * 12 Campath-1H 0.3 mg/kg intravenously (IV) over 2 hours
* 11 Campath-1H 0.3 mg/kg intravenously over 2 hours
* 10 Campath-1H 0.3 mg/kg intravenously over 2 hours
* 9 Busulfan \<12 kg: 2.2 mg/kg/dose IV every 12 hours \>12 kg: 1.6 mg/kg/dose IV every 12 hours
* 8 Busulfan \<12 kg: 2.2 mg/kg/dose IV every 12 hours \>12 kg: 1.6 mg/kg/dose IV every 12 hours
* 7 "Rest"
* 6 Clofarabine 40 mg/m2 intravenously over 2 hours
* 5 Clofarabine 40 mg/m2 intravenously over 2 hours
* 4 Clofarabine 40 mg/m2 intravenously over 2 hours
* 3 Clofarabine 40 mg/m2 intravenously over 2 hours
* 2 Clofarabine 40 mg/m2 intravenously over 2 hours intervention 3: Dose 500 cGy via anteroposterior (AP) and posteroanterior (PA) fields (250 cGy AP and 250 cGy PA).

Protocol document: