Conditions: Osteopetrosis
Keywords: Osteopetrosis Autosomal recessive bone disease Haploidentical stem cell transplantation Allogeneic stem cell transplantation T-cell depletion methodology Miltenyi Biotec CliniMACS stem cell selection device
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 15
Healthy volunteers: no

Brief summary:
Malignant infantile osteopetrosis (MIOP) is a rare fatal genetic disorder that is characterized by the bone's inability to regulate remodeling. The only curative therapy is hematopoietic stem cell transplantation. Stem cells provided from an HLA identical matched sibling donor is the standard of care, but not feasible for the majority of patients. In addition, due to the potentially rapid progression of this disease, the time to identify a suitable HLA matched unrelated donor is not optimal. Therefore this study is designed to test the hypothesis that children with osteopetrosis can properly engraft hematopoietic stem cells that are donated from a partially matched parental donor, or "haploidentical" stem cell donor that are processed on the investigational device, CliniMACS selection system.

Detailed description:
The primary objective of this trial will be answered strictly by those patients enrolled who receive a haploidentical stem cell donor graft.

Patients with a matched sibling donor will be offered participation in this clinical trial and will receive a standard myeloablative conditioning regimen followed by the infusion of an unmanipulated bone marrow graft. However, data from these transplant recipients will be reported in a descriptive manner only.

Secondary Objectives in this trial include the following:

* To describe the outcome of children with MIOP who receive hematopoietic stem cells from a matched sibling donor or a haploidentical donor utilizing a uniform approach one year from transplant
* To estimate the fraction of children with MIOP who have a genetic defect correlating to the osteopetrosis phenotype
* To assess carrier-state of the genetic mutation in parents with an affected child
* To assess carrier-state of the genetic mutation in siblings of affected children
* To estimate the effect of age at the time of hematopoietic stem cell transplantation on the overall outcome of children with MIOP
* To describe the kinetics of select cytokine expression before and after transplantation

Arms:
arm 1: None

Interventions: intervention 1: Stem Cell Transplantation intervention 2: Miltenyi Biotec CliniMACS intervention 3: Systemic chemotherapy and antibodies
Intervention descriptions: intervention 1: An infusion of HLA partially matched family member donor stem cells processed through the use of the investigational Miltenyi Biotec CliniMACS device. intervention 2: Stem cell selection device intervention 3: Haploidentical stem cell transplant recipients will receive a reduced intensity conditioning regimen consisting of OKT-3, Fludarabine, Thiotepa , and Melphalan followed by an infusion of a T-cell depleted donor stem cell product. Rituximab will be administered within 24 hours of the infusion in an effort to prevent post transplantation lymphoproliferative disorders (PTLPD). In addition to T-cell depletion of the donor product, cyclosporine will be provided as prophylaxis for (GVHD)Graft versus Host Disease

Recipients of a matched sibling donor product will receive a myeloablative conditioning regimen consisting of busulfan and cyclophosphamide. Cyclosporine will be administered for GVHD prophylaxis.

Protocol document: