title: Targeted Busulfan therapy with a steady-state concentration of 600-700 ng/mL in patients with sickle cell disease receiving HLA-identical sibling bone marrow transplant.
abstract: Busulfan (BU) has a narrow therapeutic window and the average concentration of BU at steady state (Css) is critical for successful engraftment in children receiving BU as part of the preparative regimen for allogeneic transplants. Sixteen patients with sickle cell disease (SCD) underwent allogeneic bone marrow transplant (BMT) from HLA-identical siblings. The preparative regimen consisted of intravenous BU 0.8-1 mg/kg/dose for 16 doses, cytoxan (CY) of 50 mg/kg daily for four doses and equine anti-thymocyte globulin (ATG) 30 mg/kg daily for three doses. BU levels were adjusted to provide a total exposure Css of 600-700 ng/mL. The median age at the time of transplant was 6.2 years (range 1.2-19.3). Fourteen (87%) patients required adjustment of the BU dose to achieve a median Css of 652 ng/mL (range 607-700). All patients achieved neutrophil and platelet engraftment without significant toxicity. Median donor engraftment at the last follow-up was 100% (range 80-100). None of the patients experienced sickle cell-related complications post transplant. With a median follow-up of 3 years (range 1.3-9), the event-free survival (EFS) and overall survival (OS) are both 100%. We conclude that targeting of BU Css between 600 and 700 ng/mL in this regimen can result in excellent and sustained engraftment in young patients with SCD.
authors: Department of Pediatrics, Inova Children's Hospital, Falls Church, VA, USA.
authors: S
authors: S
authors: Maheshwari
authors: Division of Hematology and Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
authors: A
authors: A
authors: Kassim
authors: Pharmacokinetics Laboratory, Seattle Cancer Care Alliance, Seattle, WA, USA.
authors: R F
authors: RF
authors: Yeh
authors: Division of Hematology/Oncology, Department of Pediatrics, Monroe Carell Jr Children's Hospital at Vanderbilt, Vanderbilt University Medical Center, Nashville, TN, USA.
authors: J
authors: J
authors: Domm
authors: Division of Hematology/Oncology, Department of Pediatrics, Monroe Carell Jr Children's Hospital at Vanderbilt, Vanderbilt University Medical Center, Nashville, TN, USA.
authors: C
authors: C
authors: Calder
authors: Division of Hematology/Oncology, Department of Pediatrics, Monroe Carell Jr Children's Hospital at Vanderbilt, Vanderbilt University Medical Center, Nashville, TN, USA.
authors: M
authors: M
authors: Evans
authors: Division of Hematology/Oncology, Department of Pediatrics, Monroe Carell Jr Children's Hospital at Vanderbilt, Vanderbilt University Medical Center, Nashville, TN, USA.
authors: B
authors: B
authors: Manes
authors: Department of Pharmacy, Vanderbilt University, Nashville, TN, USA.
authors: K
authors: K
authors: Bruce
authors: Division of Hematology/Oncology, Department of Pediatrics, Monroe Carell Jr Children's Hospital at Vanderbilt, Vanderbilt University Medical Center, Nashville, TN, USA.
authors: V
authors: V
authors: Brown
authors: Division of Hematology/Oncology, Department of Pediatrics, Monroe Carell Jr Children's Hospital at Vanderbilt, Vanderbilt University Medical Center, Nashville, TN, USA.
authors: R
authors: R
authors: Ho
authors: Division of Hematology/Oncology, Department of Pediatrics, Monroe Carell Jr Children's Hospital at Vanderbilt, Vanderbilt University Medical Center, Nashville, TN, USA.
authors: H
authors: H
authors: Frangoul
authors: Department of Hematology and Oncology, Children's National Medical Center, Center for Cancer and Blood Disorders of Northern Virginia, Falls Church, VA, USA.
authors: E
authors: E
authors: Yang
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000755:Anemia, Sickle Cell / Q000188:drug therapy* / Q000628:therapy*; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D016026:Bone Marrow Transplantation; D002066:Busulfan / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006680:HLA Antigens / Q000737:chemistry*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007223:Infant; D008297:Male; D009504:Neutrophils / Q000166:cytology; D035781:Siblings; D016896:Treatment Outcome
chemical_list: D000961:Antilymphocyte Serum; D006680:HLA Antigens; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D002066:Busulfan