Plerixafor alone for the mobilization and transplantation of HLA-matched sibling donor hematopoietic stem cells.

• Authors: Yi-Bin Chen, Massachusetts General Hospital; Jennifer Le-Rademacher, Medical College of Wisconsin; Ruta Brazauskas, Medical College of Wisconsin; Deidre M. Kiefer, Medical College of Wisconsin; Mehdi Hamadani, Medical College of Wisconsin; John F. DiPersio, Barnes Jewish Hospital; Mark R. Litzow, Mayo Clinic; Michael Craig, West Virginia University; Mitchell E. Horwitz, Duke University; Andrew S. Artz, University of Chicago; Brian L. McClune, University of Minnesota; Hugo F. Fernandez, H. Lee Moffitt Cancer Center; Hien Kim Duong, Cleveland Clinic Foundation; Hati Kobusingye, Medical College of Wisconsin; Mandi Proue, Medical College of Wisconsin; Rebecca J. Drexler, Medical College of Wisconsin; Mary M. Horowitz, Medical College of Wisconsin; Bronwen E. Shaw, Medical College of Wisconsin; John P. Miller, Medical College of Wisconsin; Sakura Hosoba, Shiga University of Medical Science; Edmund Waller, Emory University; Steven M. Devine, Medical College of Wisconsin
• Journal Title: Blood Advances
• Volume: Volume 3, Number 6
• Publisher: American Society of Hematology: Blood Advances | 2019-03-26, Pages 875-883
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1182/bloodadvances.2018027599
• Subjects: Biology, Cell; Health Sciences, Medicine and Surgery; Biology, Genetics
• Keywords: Plerixafor-based mobilization; toxicity; G-CSF; CD34+; cells; mobilization; allograft; clinical outcomes

Abstract

Plerixafor, a direct antagonist of CXCR4/stromal-derived factor 1, can safely and rapidly mobilize allografts without the use of granulocyte colony-stimulating factor (G-CSF). We conducted a phase 2, multicenter, prospective study of plerixafor-mobilized HLA-identical sibling allografts for allogeneic hematopoietic cell transplantation in recipients with hematological malignancies. Donors (n = 64) were treated with subcutaneous plerixafor (240 µg/kg) and started leukapheresis (LP) 4 hours later. The primary objective was to determine the proportion of donors who were successfully mobilized: defined as collection of ≥2.0 × 106 CD34+ cells per kilogram recipient weight in ≤2 LP sessions. Recipients subsequently received reduced intensity (RIC; n = 33) or myeloablative (MAC; n = 30) conditioning. Sixty-three of 64 (98%) donors achieved the primary objective. The median CD34+ cell dose per kilogram recipient weight collected within 2 days was 4.7 (0.9-9.6). Plerixafor was well tolerated with only grade 1 or 2 drug-related adverse events noted. Bone pain was not observed. Plerixafor-mobilized grafts engrafted promptly. One-year progression-free and overall survivals were 53% (95% confidence interval [CI], 36% to 71%) and 63% (95% CI, 46% to 79%) for MAC and 64% (95% CI, 47% to 79%) and 70% (95% CI, 53% to 84%) for RIC recipients, respectively. Donor toxicity was reduced relative to G-CSF mobilized related donors. This is the first multicenter trial to demonstrate that, as an alternative to G-CSF, plerixafor rapidly and safely mobilizes sufficient numbers of CD34+ cells from matched sibling donors for HCT. Engraftment was prompt, and outcomes in recipients were encouraging. This trial was registered at clinicaltrials.gov as #NCT01696461.