RATIONALE: Giving chemotherapy, such as busulfan, fludarabine, and melphalan, before a donor umbilical cord blood stem cell transplant helps stop the growth of abnormal or cancer cells and prepares the patient's bone marrow for the stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil may stop this from happening. PURPOSE: This phase II trial is studying how well combination chemotherapy followed by a donor umbilical cord blood transplant works in treating infants with high-risk acute leukemia or myelodysplastic syndromes.
OBJECTIVES: Primary * Determine the incidence of engraftment, defined as achieving donor-derived neutrophil count \> 500/mm³ by day 42, in infants with high-risk acute myeloid leukemia, acute lymphoblastic leukemia, or myelodysplastic syndromes treated with a non-irradiation containing myeloablative conditioning regimen comprising busulfan, fludarabine, and melphalan followed by double umbilical cord blood transplantation (UCBT) with two partially HLA-matched units. Secondary Objectives * Determine the incidence of transplant-related mortality (TRM) at 6 months after UCBT * Evaluate pattern of chimerism after double UCBT * Determine the incidence of platelet engraftment at 1 year after UCBT * Determine the incidence of acute graft-versus-host disease (GVHD) grade II-IV and grade III-IV at day 100 after UCBT * Evaluate the developmental outcome after UCBT Transplant Related Objectives * Determine the incidence of chronic GVHD at 1 year after UCBT * Determine the survival and disease free survival at 1 and 2 years after UCBT * Determine the incidence relapse at 1 and 2 years after UCBT
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
34
All patients will receive G-CSF 5 mcg/kg/day intravenous (IV) (dose rounded to vial size) based on the actual body weight IV beginning on day +1 after umbilical cord blood (UCB) infusion. G-CSF will be administered daily until the absolute neutrophil count (ANC) exceeds 2.5 x 10\^9/L for three consecutive days and then discontinued. If the ANC decreases to \<1.0 x 10\^9/L, G-CSF will be reinstituted.
Administered 1.1 mg/kg if \<12 kg intravenous (IV) every 6 hours (0.8 mg/kg if \>12 kg IV every 6 hours on Days -8 through -5.
Patients will receive cyclosporine (CSA) therapy beginning on day -3 maintaining a level of \>200 ng/mL. For children \< 40 kg the initial dose will be 2.5 mg/kg intravenous (IV) over 2 hours every 8 hours.
Administered 25 mg/m\^2 intravenous (IV) over 60 minutes on Days -4 through -2.
Administered 60 mg/m\^2 intravenous (IV) over 30 minutes on Days -4 through -2.
All patients will begin mycophenolate mofetil (MMF) on day -3. Patients \<45 kilograms will receive MMF at the dose of 15 mg/kg/dose every 8 hours (max dose 1gm/dose) orally or intravenously (PO or IV).
The product is infused via IV drip directly into the central line without a needle, pump or filter on Day 0.
Masonic Cancer Center, University of Minnesota
Minneapolis, Minnesota, United States
Incidence of Engraftment
Defined as achieving donor derived neutrophil count \>500/uL by day 42 in young children with leukemia or myelodysplastic syndrome undergoing a partially matched single unit umbilical cord blood transplant (UCBT) after a myeloablative preparative regimen consisting of busulfan, melphalan and fludarabine.
Time frame: Day 42 After Transplant
Incidence of Transplant-related Mortality (TRM)
defined as death due to transplant
Time frame: at 6 months after transplant
Incidence of Platelet Engraftment
defined as platelet count \> 50,000
Time frame: at 1 year after transplant
Incidence of Acute Graft-versus-host Disease (GVHD) Grade II-IV and Grade III-IV
Graft-versus-host disease (GVHD) is a common complication of allogeneic bone marrow transplantation in which functional immune cells in the transplanted marrow recognize the recipient as "foreign" and mount an immunologic attack.
Time frame: Day 100 After Transplant
Incidence of Chronic Graft-versus-host Disease (GVHD)
Graft-versus-host disease (GVHD) is a common complication of allogeneic bone marrow transplantation in which functional immune cells in the transplanted marrow recognize the recipient as "foreign" and mount an immunologic attack.
Time frame: 1 Year After Transplant
Incidence of Relapse
defined using standard criteria (bone marrow blast count and cytogenetics).
Time frame: 1 and 2 years after transplant
Overall Survival
Alive after transplant.
Time frame: at 1 and 2 years after transplant
Disease-free Survival
defined as patients who are alive and in hematological remission.
Time frame: at 1 and 2 years after transplant
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.