RATIONALE: Giving chemotherapy and total marrow and lymphoid irradiation before allogeneic hematopoietic cell transplant helps stop the growth of leukemia cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may achieve brand new hematopoietic recovery. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells, resulting in graft versus-host disease. PURPOSE: This study is to evaluate the toxicity and efficacy of total marrow and lymphoid irradiation conditioning when given together with combination chemotherapy and allogeneic peripheral blood stem cell transplant in treating patients with myelodysplastic syndrome or acute leukemia.
Patient receives preparative therapy including cyclophosphamide and total body irradiation (TBI) of 10 Gy or total marrow and lymphoid irradiation (TMLI) of 12-20 Gy, and starts immunosuppressive therapy using cyclosporine or tacrolimus, methotrexate-based prophylaxes, followed by peripheral blood stem cell transplantation and granulocyte colony-stimulating factor administration.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
191
Drug: Cyclophosphamide 60 mg/kg/day intravenous x 2 days pre-transplant, total dose 120 mg/kg Drug: Cyclosporine or tacrolimus Beginning on Day -1 pre-transplant maintaining a level of 150-250 ng/ml or 5-10 ng/ml respectively. Cyclosporine or tacrolimus dosing will be monitored and altered as clinically appropriate by physician, and discontinue at approximately day + 180 post-transplant. Drug: Methotrexate 15 mg/m2 intravenous on days 1, 10 mg/m2 intravenous on days 3, 6 and 11 after transplantation. Intervention: Total Body Irradiation Dose of 10 Gy TBI (fraction size of 5 Gy given once a day on days -2 and -1). Procedure: Peripheral blood stem cell transplantation product will be infused via intravenous drip on Day 0.
Drug: Cyclophosphamide 60 mg/kg/day intravenous x 2 days pre-transplant, total dose 120 mg/kg Drug: Cyclosporine or tacrolimus Beginning on Day -1 pre-transplant maintaining a level of 150-250 ng/ml or 5-10 ng/ml respectively. Cyclosporine or tacrolimus dosing will be monitored and altered as clinically appropriate by physician, and discontinue at approximately day + 180 post-transplant. Drug: Methotrexate 15 mg/m2 intravenous on days 1, 10 mg/m2 intravenous on days 3, 6 and 11 after transplantation. Intervention: Total Marrow and Lymphoid Irradiation Dose of 12 Gy TMLI (fraction size of 4 Gy given once a day on days -6, -5 and -4). Procedure: Peripheral blood stem cell transplantation product will be infused via intravenous drip on Day 0.
Affiliated Hospital to Academy of Military Medical Sciences (307 Hospital of PLA)
Beijing, Beijing Municipality, China
RECRUITINGIncidence of toxicity, scored on National Cancer Institute Common Terminology Criteria version 4.03
Toxicity information recorded will include the type, severity, and the probable association with the study regimen.
Time frame: Up to 100 days after stem cell infusion
Hematopoietic reconstruction
Neutrophil engraftment is defined as the first day of three consecutive days where the neutrophil count (absolute neutrophil count) is 1,000 cells/mm3 (1.0×109/L) or greater. Platelet engraftment is defined as 20,000/mm3 (20×109/L) for 3 consecutive days unsupported by a platelet transfusion.
Time frame: Day +30
Incidence of grade II-IV acute graft-versus-host disease (GVHD) after transplantation
Acute Graft-Versus-Host Disease is a severe short-term complication created by infusion of donor cells into a foreign host.
Time frame: Day +100
Incidence of chronic GVHD after transplantation
Chronic Graft-Versus-Host Disease is a severe long-term complication created by infusion of donor cells into a foreign host.
Time frame: 1 Year
Menstrual recovery after transplantation
The percentage of female patients who have resumed menses is usually considered as related to ovarian function.
Time frame: 1 Year and 2 years
Overall survival after transplantation
The percentage of people in a study or treatment group who are alive for a certain period of time after they were diagnosed with or treated for a disease, such as cancer.
Time frame: 1 year and 2 years
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