Haematologica
Haematologica
5 years ago

Safety and efficacy of plerixafor dose escalation for the mobilization of CD34+ hematopoietic progenitor cells in patients with sickle cell disease: interim results.

Patricia A Shi, Sylvie Wiener Fedus, Karina Yazdanbakhsh, Vijay Nandi, Tsiporah Shore, Koen van Besien, Caterina Minniti, Audrey Mauguen, Fabiana Perna, Farid Boulad, Danielle Guarneri, June Greenberg, Mihaela Barbu-Stevanovic, Michel Sadelain
Gene therapy for sickle cell disease is limited by the yield of hematopoietic progenitor cell harvest for transduction or gene editing. We therefore performed a Phase I dose-escalation study of the hematopoietic progenitor cell mobilizing agent plerixafor to evaluate the efficacy and safety of standard dosing on peripheral blood CD34+ cell mobilization. Of 15 patients enrolled to date, only one was chronically transfused and 10 were on hydroxyurea. Of 8 patients achieving a CD34+ cell concentration >30 cells/μl, 6 were on hydroxyurea. There was no clear dose response to increasing plerixafor dosage. There was a low rate of serious adverse events; two patients developed vaso-occlusive crises, at 80 mg/kg and 240 mg/kg, respectively. Hydroxyurea may have contributed to the limited CD34+ mobilization by affecting baseline peripheral blood CD34, which highly correlated with peak peripheral blood CD34. Plerixafor administration did not induce significant increases in the fraction of activated neutrophils, monocytes, or platelets. However, increased neutrophils positive for activated β2 integrin and Mac-1 were associated with serious adverse events. In summary, plerixafor was well tolerated but did not achieve consistent CD34+ cell mobilization in this patient cohort where most were actively treated with hydroxyurea and only one was chronically transfused. The study will continue to dose escalate plerixafor with modification of hydroxyurea administration. clinicaltrials.gov identifier: NCT02193191.

Publisher URL: http://doi.org/10.3324/haematol.2017.187047

DOI: 10.3324/haematol.2017.187047

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