Abstract
Gene therapy for sickle cell disease is limited by the yield of hematopoietic progenitor cells that can be harvested 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 ten were on hydroxyurea. Of eight patients who achieved a CD34+ cell concentration >30 cells/μL, six 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 the doses of 80 μg/kg and 240 μg/kg. Hydroxyurea may have contributed to the limited CD34+ mobilization by affecting baseline peripheral blood CD34 counts, which correlated strongly with peak peripheral blood CD34 counts. 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 cohort of patients, most of whom were being actively treated with hydroxyurea and only one was chronically transfused. The study will continue with escalation of the dose of plerixafor and modification of hydroxyurea administration. Clinicaltrials.gov identifier: NCT02193191.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 770-777 |
| Number of pages | 8 |
| Journal | Haematologica |
| Volume | 103 |
| Issue number | 5 |
| DOIs | |
| State | Published - Apr 30 2018 |
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ASJC Scopus subject areas
- Hematology
Cite this
Safety and efficacy of plerixafor dose escalation for the mobilization of cd34+ hematopoietic progenitor cells in patients with sickle cell disease : Interim results. / Boulad, Farid; Shore, Tsiporah; van Besien, Koen; Minniti, Caterina P.; Barbu-Stevanovic, Mihaela; Fedus, Sylvie Wiener; Perna, Fabiana; Greenberg, June; Guarneri, Danielle; Nandi, Vijay; Mauguen, Audrey; Yazdanbakhsh, Karina; Sadelain, Michel; Shi, Patricia A.
In: Haematologica, Vol. 103, No. 5, 30.04.2018, p. 770-777.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Safety and efficacy of plerixafor dose escalation for the mobilization of cd34+ hematopoietic progenitor cells in patients with sickle cell disease
T2 - Interim results
AU - Boulad, Farid
AU - Shore, Tsiporah
AU - van Besien, Koen
AU - Minniti, Caterina P.
AU - Barbu-Stevanovic, Mihaela
AU - Fedus, Sylvie Wiener
AU - Perna, Fabiana
AU - Greenberg, June
AU - Guarneri, Danielle
AU - Nandi, Vijay
AU - Mauguen, Audrey
AU - Yazdanbakhsh, Karina
AU - Sadelain, Michel
AU - Shi, Patricia A.
PY - 2018/4/30
Y1 - 2018/4/30
N2 - Gene therapy for sickle cell disease is limited by the yield of hematopoietic progenitor cells that can be harvested 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 ten were on hydroxyurea. Of eight patients who achieved a CD34+ cell concentration >30 cells/μL, six 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 the doses of 80 μg/kg and 240 μg/kg. Hydroxyurea may have contributed to the limited CD34+ mobilization by affecting baseline peripheral blood CD34 counts, which correlated strongly with peak peripheral blood CD34 counts. 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 cohort of patients, most of whom were being actively treated with hydroxyurea and only one was chronically transfused. The study will continue with escalation of the dose of plerixafor and modification of hydroxyurea administration. Clinicaltrials.gov identifier: NCT02193191.
AB - Gene therapy for sickle cell disease is limited by the yield of hematopoietic progenitor cells that can be harvested 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 ten were on hydroxyurea. Of eight patients who achieved a CD34+ cell concentration >30 cells/μL, six 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 the doses of 80 μg/kg and 240 μg/kg. Hydroxyurea may have contributed to the limited CD34+ mobilization by affecting baseline peripheral blood CD34 counts, which correlated strongly with peak peripheral blood CD34 counts. 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 cohort of patients, most of whom were being actively treated with hydroxyurea and only one was chronically transfused. The study will continue with escalation of the dose of plerixafor and modification of hydroxyurea administration. Clinicaltrials.gov identifier: NCT02193191.
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U2 - 10.3324/haematol.2017.187047
DO - 10.3324/haematol.2017.187047
M3 - Article
VL - 103
SP - 770
EP - 777
JO - Haematologica
JF - Haematologica
SN - 0390-6078
IS - 5
ER -