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

Yi Bin Chen, Jennifer Le-Rademacher, Ruta Brazauskas, Deidre M. Kiefer, Mehdi Hamadani, John F. DiPersio, Mark R. Litzow, Michael Craig, Mitchell E. Horwitz, Andrew S. Artz, Brian L. McClune, Hugo F. Fernandez, Hien Kim Duong, Hati Kobusingye, Mandi Proue, Rebecca J. Drexler, Mary M. Horowitz, Bronwen E. Shaw, John P. Miller, Sakura HosobaEdmund K. Waller, Steven M. Devine

Research output: Contribution to journalArticle

1 Scopus 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 5 64) were treated with subcutaneous plerixafor (240 mg/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 3 106 CD341 cells per kilogram recipient weight in #2 LP sessions. Recipients subsequently received reduced intensity (RIC; n 5 33) or myeloablative (MAC; n 5 30) conditioning. Sixty-three of 64 (98%) donors achieved the primary objective. The median CD341 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 CD341 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.

Original languageEnglish (US)
Pages (from-to)875-883
Number of pages9
JournalBlood Advances
Volume3
Issue number6
DOIs
StatePublished - Mar 26 2019

ASJC Scopus subject areas

  • Hematology

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    Chen, Y. B., Le-Rademacher, J., Brazauskas, R., Kiefer, D. M., Hamadani, M., DiPersio, J. F., Litzow, M. R., Craig, M., Horwitz, M. E., Artz, A. S., McClune, B. L., Fernandez, H. F., Duong, H. K., Kobusingye, H., Proue, M., Drexler, R. J., Horowitz, M. M., Shaw, B. E., Miller, J. P., ... Devine, S. M. (2019). Plerixafor alone for the mobilization and transplantation of HLA-matched sibling donor hematopoietic stem cells. Blood Advances, 3(6), 875-883. https://doi.org/10.1182/bloodadvances.2018027599