Faculty Collaboration Database

Plerixafor alone for the mobilization and transplantation of HLA-matched sibling donor hematopoietic stem cells. Blood Adv 2019 Mar 26;3(6):875-883

Date

03/21/2019

Pubmed ID

30890544

Pubmed Central ID

PMC6436017

DOI

10.1182/bloodadvances.2018027599

Scopus ID

2-s2.0-85072746485 (requires institutional sign-in at Scopus site)   29 Citations

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.

Author List

Chen YB, Le-Rademacher J, Brazauskas R, Kiefer DM, Hamadani M, DiPersio JF, Litzow MR, Craig M, Horwitz ME, Artz AS, McClune BL, Fernandez HF, Duong HK, Kobusingye H, Proue M, Drexler RJ, Horowitz MM, Shaw BE, Miller JP, Hosoba S, Waller EK, Devine SM

Authors

Ruta Brazauskas PhD Associate Professor in the Data Science Institute department at Medical College of Wisconsin
Mehdi H. Hamadani MD Professor in the Medicine department at Medical College of Wisconsin
Mary M. Horowitz MD, MS Professor in the Medicine department at Medical College of Wisconsin
Bronwen E. Shaw MBChB, PhD Center Director, Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Antigens, CD34
Benzylamines
Hematologic Neoplasms
Hematopoietic Stem Cell Mobilization
Hematopoietic Stem Cell Transplantation
Heterocyclic Compounds
Histocompatibility
Humans
Middle Aged
Siblings
Tissue Donors
Transplantation, Homologous
Treatment Outcome