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

Safety and efficacy of plerixafor dose escalation for the mobilization of CD34+ hematopoietic progenitor cells in patients with sickle cell disease: interim results. Haematologica. 2018 Feb 01;: Authors: Boulad F, Shore T, van Besien K, Minniti C, Barbu-Stevanovic M, Wiener Fedus S, Perna F, Greenberg J, Guarneri D, Nandi V, Mauguen A, Yazdanbakhsh K, Sadelain M, Shi PA Abstract 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...
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research