SR-1 transiently depletes high-risk MDS cells and permits engraftment of second human UCB HSC graft in high-risk MDS-xenografted mice. (A) SR-1 transiently depletes human blood cells derived from high-risk MDS HSCs in vivo, as shown by chimerism of human myeloid (hCD13/CD33⁺) cells on pretreatment day 0 and 8 days and 8 weeks after completion of treatment with 500 μg of SR-1 administered IV on days 1, 3, 5, and 7. *P < .001 compared with day 0 (Student t test) (n = 4, SR-1 treated). (B) Total human chimerism (human CD45⁺) as well as distribution of myeloid (human CD45⁺CD13/33⁺), B-cell (human CD45⁺CD19⁺), and T-cell (human CD45⁺CD3⁺) chimerism in BM of high-risk MDS-xenografted mice treated with SR-1 mAb on days 1, 3, 5, and 7, and then transplanted on day 15 with a second normal human UCB HSC graft. Chimerism was measured 12 weeks after second normal human UCB HSC transplant (n = 4, SR-1 treated). (C) Frequency of cytogenetically abnormal clone (−7, del(5q), or +8), as detected by FISH within human cells FACS-isolated from BM of high-risk MDS-xenografted mice treated with SR-1 mAb on days 1, 3, 5, and 7 and then transplanted on day 15 with a second normal human UCB HSC graft. Cells were analyzed 12 weeks after second normal human UCB HSC transplant (n = 4, SR-1 treated).