Conditions: Aplastic Anemia
Keywords: Severe Aplastic Anemia Bone Marrow Failure Stem Cell Transplantation Fludarabine Cyclophosphamide Antithymocyte Globulin SAA ATG Cytoxan Neosar Fludarabine Phosphate Thymoglobulin
Allocation: NON_RANDOMIZED | Intervention model: SINGLE_GROUP
Enrollment: 9
Healthy volunteers: no

Brief summary:
Primary Objectives:

1. To determine the feasibility and toxicity of employing purine-analog based conditioning for allogeneic donor stem cell transplantation in patients with severe aplastic anemia (AA).
2. To determine the engraftment kinetics and degree of chimerism that can be achieved with this strategy.

Detailed description:
Before treatment starts, patients will have their bone marrow checked and will have lung, heart, and kidney tests.

Patients in this study will receive the drugs fludarabine, cyclophosphamide, and antithymocyte globulin by vein through a previously inserted plastic catheter that extends into the large chest vein. Fludarabine will be given daily for four days, cyclophosphamide will given daily for four days, and antithymocyte globulin will be given daily for four days (three days for related donor transplants).

Two days after the last dose of cyclophosphamide, donor marrow or stem cells will be infused through a catheter (thin plastic tube). Drugs will be given to lower the chance of an allergic reaction to the stem cells. Patients will also get shots of filgrastim (a drug that helps white blood cell growth) and antibiotics by mouth. The blood cell counts will fall to low levels during the first 2 weeks when patients may need transfusions of red blood cells and platelets. The chemotherapy will be given in the hospital. After the infusion of stem cells, patients will be monitored in the hospital. They will later be closely followed as outpatients and will be required to remain in the Houston area for about three months after the transplant.

Drugs (cyclosporine and methotrexate) to lower the chance of graft-versus-host disease will be given. Cyclosporine will be given as a continuous infusion starting 2 days before transplantation. Methotrexate will be given through the catheter on Days 1, 3, 6 and 11 after transplantation. Cyclosporine will be given as pills when the patient is able to swallow. Cyclosporine will be continued for no less than 6 months after transplantation after which it will be gradually stopped. The drug tacrolimus may be used instead of cyclosporine.

Blood, urine, bone marrow, and x-ray exams will be done as needed to monitor the results of bone marrow transplantation. Patients may require blood and platelet transfusions. Blood tests will be done daily while hospitalized and several times a week until the blood counts recover. Bone marrow aspiration and biopsies will be performed before the transplant, when the donated cells show signs of engraftment, and at other times during the next 1 to 3 years. They will be done to evaluate the growth of the transplant marrow, possible recurrence of malignancy, and recovery of immunity. If this treatment proves unsuccessful in more than three of the first ten patients, the study will be stopped.

This is an investigational study. The FDA has approved all of the drugs in this study for other indications. Up to 30 patients will be treated on this study. All will be enrolled at M.D. Anderson.

Arms:
arm 1: Fludarabine 30 mg/m\^2/day by vein (IV), Cyclophosphamide IV 300 mg/m\^2/day, ATG (Antithymocyte Globulin) IV 3.75 mg/kg/day

Interventions: intervention 1: Fludarabine intervention 2: Cyclophosphamide intervention 3: Antithymocyte Globulin
Intervention descriptions: intervention 1: 30 mg/m\^2 by vein daily over 30 minutes intervention 2: 300 mg/m\^2 by vein daily over 2 hours intervention 3: 3.75 mg/kg by vein daily over 4 hours

Protocol document: