Fludarabine-Based Conditioning for Matched Related Donor Bone Marrow Transplantation in Patients With Bone Marrow Failure Syndromes
Children's Hospital of Philadelphia
Summary
This is a pilot study to determine whether fludarabine-based reduced intensity conditioning (RIC) regimens facilitate successful donor engraftment of patients with acquired aplastic anemia (AA) and Inherited bone marrow failure (iBMF) syndromes undergoing Matched related donor bone marrow transplant (MRD-BMT).
Description
Acquired AA patients will receive the experimental regimen of fludarabine with dose-reduced cyclophosphamide, with results in this prospective single arm experimental group evaluated in the context of our institutional historical experience using HD Cy regimens as well as published outcomes using both fludarabine and high-dose cyclophosphamide-based regimens for MRD-BMT in aplastic anemia. iBMF syndrome patients will receive one of two fludarabine-containing regimens based on disease characteristics, and our outcomes will be compared to previously published data using a variety of regimens. Gr…
Eligibility
- Age range
- Up to 22 years
- Sex
- All
- Healthy volunteers
- No
Patients 0-22 years with acquired aplastic anemia or a diagnosed inherited bone marrow failure syndrome, and a fully Human leukocyte antigen (HLA)-matched (10/10) related donor. Inclusion Criteria: Patient: 1. Ages 0-22 years at time of enrollment 2. Diseases: * Patients with severe or very severe acquired AA, defined by: * Bone marrow biopsy demonstrating cellularity of \<25% (at least 2 weeks from last dose of G-CSF), in addition to 2 of the following: absolute neutrophil count (ANC) \<500/µL, platelets \< 20,000/µL and absolute reticulocytes \<40,000/µL * Negative evaluati…
Interventions
- OtherMRD-BMT with Fludarabine-based RIC for Acquired AA
Fludarabine: Dose: 30mg/m2/day (\<10kg will receive 1mg/kg/day) Days: -7, -6, -5, -4, -3 Cyclophosphamide: Dose: 60mg/kg/day Days: -5, -4 Thymoglobulin: Dose: 3mg/kg/day Days: -4, -3, -2 Bone marrow infusion: Day 0
- OtherMRD-BMT with Fludarabine-based RIC for iBMF with trilineage aplasia
Fludarabine: Dose: 30mg/m2/day (\<10kg will receive 1mg/kg/day) Days: -7, -6, -5, -4, -3 Cyclophosphamide: Dose: 10 mg/kg/day Days: -6, -5, -4, -3 Thymoglobulin: Dose: 3mg/kg/day Days: -4, -3, -2 Bone marrow infusion: Day 0
- OtherMRD-BMT with Fludarabine-based RIC for iBMF without trilineage aplasia
Fludarabine: Dose: 30mg/m2/day (\<10kg will receive 1mg/kg/day) Days: -6, -5, -4, -3, -2 Busulfan: Dose: every 6 hours for a total of 12 doses with dosing adjustments to achieve a steady state concentration of 900-1200ng/mL OR daily for a total of 3 doses targeting AUC 3600-6000 (micromole/liter)\*minute Days: -7, -6, -5, -4 Thymoglobulin: Dose: 3mg/kg/day Days: -10, -9, -8 Bone marrow infusion: Day 0
Location
- Children's Hospital of PhiladelphiaPhiladelphia, Pennsylvania