NYMC Faculty Publications
DOI
10.18632/oncotarget.22739
Journal Title
Oncotarget
First Page
110350
Last Page
110357
Document Type
Article
Publication Date
11-27-2017
Department
Pediatrics
Abstract
Delayed engraftment remains a limitation of umbilical cord blood (UCB) transplantation. We previously showed that inhibition of dipeptidylpeptidase (DPP)-4 using sitagliptin 600 mg daily was safe with encouraging results on engraftment, but inhibition was not sustained. We evaluated the efficacy and feasibility of higher doses of sitagliptin to enhance engraftment of UCB in patients with hematological cancers. Fifteen patients, median age 41 (range, 18-59) years, received single UCB grafts matched at 4 (n=11) or 5 (n=4) of 6 HLA loci with median nucleated cell dose of 3.5 (range, 2.57-4.57) x10(7)/kg. Sitagliptin 600 mg every 12 hours was administered days -1 to +2. All patients engrafted by day 30, with 12 (80%) engrafting by day 21. The median time to neutrophil engraftment was 19 (range, 12-30) days. Plasma DPP-4 activity was better inhibited with a mean residual trough DPP-4 activity of 70%+/-19%. Compared to patients previously treated with 600 mg/day, sitagliptin 600 mg every 12 hours appeared to improve engraftment, supporting the hypothesis that more sustained DPP-4 inhibition is required. In-vivo inhibition of DPP-4 using high-dose sitagliptin compares favorably with other approaches to enhance UCB engraftment with greater simplicity, and may show synergy in combination with other strategies.
Recommended Citation
Farag, S., Nelson, R., Cairo, M., O'Leary, H., Zhang, S., Huntley, C., Delgado, D., Schwartz, J., Zaid, M., Abonour, R., Robertson, M., & Broxmeyer, H. (2017). High-dose Sitagliptin for Systemic Inhibition of Dipeptidylpeptidase-4 to Enhance Engraftment of Single Cord Umbilical Cord Blood Transplantation. Oncotarget, 8 (66), 110350-110357. https://doi.org/10.18632/oncotarget.22739
Publisher's Statement
Originally published in Oncotarget, 8(66), 110350-110357. The original material can be found here.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.