Pharmacokinetics of Basiliximab for the Prevention of Graft-versus-Host Disease in Patients Undergoing Hematopoietic Cell Transplantation with Minimal-Intensity Cyclophosphamide and Fludarabine.

STUDY OBJECTIVE: Basiliximab is an immunosuppressive monoclonal antibody used for rejection prevention following solid organ transplantation; the pharmacokinetics (PK) of basiliximab in this setting are known. Basiliximab may also be used for prophylaxis and treatment of graft-versus-host disease (GVHD) in patients undergoing allogeneic hematopoietic cell transplantation (HCT); however, the PK of basiliximab in this setting are not known. Clinical transplant providers expect variation in the volume of distribution and clearance after nonmyeloablative allogeneic transplantation (NMAT) compared with solid organ transplantation. Blood loss, organ site-specific antibody accumulation, and differences in blood product use during the two transplantation approaches may generate differences in basiliximab PK. Therefore, the objective of this study was to describe the PK of basiliximab after its addition to a minimally intense NMAT regimen, in conjunction with cyclosporine, for GVHD prophylaxis in patients with hematologic malignancies. DESIGN: Population PK analysis of a single-center, single-arm, phase II clinical trial. SETTING: Academic cancer research center. PATIENTS: Fourteen adults with hematologic malignancies (acute myeloid leukemia, acute lymphoblastic leukemia, chronic lymphocytic leukemia, myelodysplastic syndrome, non-Hodgkin's lymphoma, Hodgkin's lymphoma, myelofibrosis, or severe aplastic anemia) and undergoing NMAT with a fully HLA-matched (10 of 10 antigen matched) related or unrelated donor. MEASUREMENTS AND MAIN RESULTS: Basiliximab was used in conjunction with cyclosporine to deplete activated T cells in vivo as GVHD prophylaxis. We developed a novel competitive enzyme-linked immunosorbent assay (ELISA) method using recombinant interleukin-2 receptor alpha-chain (IL-2Ra) and a commercially available soluble sIL-2R ELISA kit to permit the quantification of serum basiliximab concentrations and characterization of the PK properties of the drug in this patient population. Using a nonlinear mixed effects model with NONMEM software, a one-compartment model with first-order elimination best described the PK, as covariate analysis using stepwise covariate modeling did not improve the base model. CONCLUSION: We suggest a one-compartment population model with first-order elimination to capture the PK profile for basiliximab for this patient population.

Experience with plerixafor for hematopoietic cell mobilization in nine patients with germ cell tumors.

STUDY OBJECTIVE: To evaluate the efficacy of plerixafor as a just-in-time therapy for patients with germ cell tumors who were identified as poor hematopoietic cell mobilizers after the initiation of apheresis. DESIGN: Case series. SETTING: National Cancer Institute-designated cancer center. PATIENTS: Nine patients with germ cell tumors who received plerixafor as an adjunct to granulocyte colony-stimulating factor (G-CSF) for hematopoietic cell mobilization in an attempt to prevent mobilization failure between January 2009 and December 2012. MEASUREMENTS AND MAIN RESULTS: Patients were heavily pretreated, having received at least four prior treatment cycles. A median of three total apheresis days (range 1-4 days) was required for all patients, but a median of two apheresis days (range 1-2 days) was needed after the initiation of plerixafor. A median of 0.9 × 106 CD34⁺ cells/kg (range 0.3-1.5 × 106 CD34⁺ cells/kg) was harvested with G-CSF mobilization alone; in addition, a median of 2.6 × 106 CD34⁺ cells/kg (range 0.6-32 × 106 CD34⁺ cells/kg) was harvested using plerixafor. All nine patients received high-dose carboplatin and etoposide followed by hematopoietic cell transplantation. The median time to neutrophil engraftment was 11 days (range 8-12 days). The median time to platelet engraftment was 16 days (range 10-22 days). CONCLUSIONS: The use of plerixafor in addition to G-CSF as just-in-time therapy permits patients with germ cell tumors to pursue potentially curative therapy with high-dose chemotherapy followed by autologous stem cell rescue.