Nicholas Fisher

Rapid mobilization of functional donor hematopoietic cells without G-CSF using AMD3100, an antagonist of the CXCR4/SDF-1 interaction

Allografts from HLA-matched sibling donors were mobilized and collected without granulocyte colony-stimulating factor (G-CSF) using AMD3100, a direct antagonist of CXCR4/stromal-derived factor 1 (SDF-1/CXCL12). Donors (N = 25) were treated with AMD3100 at a dose of 240 mug/kg by subcutaneous injection, and leukapheresis was then initiated just 4 hours later. Two-thirds of the donors collected an allograft with a CD34(+) cell dose sufficient for transplantation after just one dose of AMD3100. No donor experienced more than grade 1 toxicity. After a myeloablative regimen, 20 patients with hematologic malignancies received allografts collected after AMD3100 alone. All patients engrafted neutrophils (median day 10) and platelets (median day 12) promptly. Acute graft-versus-host disease (GVHD) grades 2 through 4 occurred in 35% of patients. One patient died due to complications related to acute GVHD. No unexpected adverse events were observed in any of the recipients. All 14 patients surviving in remission have robust trilineage hematopoiesis and are transfusion-free with a median follow-up of 277 days (range, 139-964 days). Direct antagonism of CXCR4 by AMD3100 may provide a more rapid and possibly less toxic and cumbersome alternative to traditional G-CSF-based mobilization in normal donors. This trial was registered as no. NCT00241358 at www.ClinicalTrials.gov.

Bortezomib administered pre-auto-SCT and as maintenance therapy post transplant for multiple myeloma: a single institution phase II study.

The appropriate induction therapy before and the role of maintenance therapy after auto-SCT for patients with multiple myeloma remain areas of active investigation. We conducted a study in 40 patients with bortezomib given sequentially pre-auto-SCT and as maintenance therapy post auto-SCT. Pre-transplant bortezomib was administered for two cycles followed by high-dose melphalan 200 mg/m2 with auto-SCT of G-CSF-mobilized PBMCs. Post transplant bortezomib was administered weekly for 5 out of 6 weeks for six cycles. No adverse effects were observed on stem cell mobilization or engraftment. An overall response rate of 83% with a CR+very good partial remission (VGPR) of 50% was observed with this approach. Three-year Kaplan–Meier estimates of disease-free survival and overall survival (OS) were 38.2 and 63.1%, respectively. Bortezomib reduced CD8+ cytotoxic T cell and CD56+ natural killer cell PBL subsets and was clinically associated with high rates of viral reactivation to varicella zoster.