BACKGROUND Poor engraftment due to low cell doses restricts the usefulness of umbilical-cord-blood transplantation. We hypothesized that engraftment would be improved by transplanting cord blood that was expanded ex vivo with mesenchymal stromal cells. METHODS We studied engraftment results in 31 adults with hematologic cancers who received transplants of 2 cord-blood units, 1 of which contained cord blood that was expanded ex vivo in cocultures with allogeneic mesenchymal stromal cells. The results in these patients were compared with those in 80 historical controls who received 2 units of unmanipulated cord blood. RESULTS Coculture with mesenchymal stromal cells led to an expansion of total nucleated cells by a median factor of 12.2 and of CD34+ cells by a median factor of 30.1. With transplantation of 1 unit each of expanded and unmanipulated cord blood, patients received a median of 8.34×107 total nucleated cells per kilogram of body weight and 1.81×106 CD34+ cells per kilogram — doses higher than in our previous transplantations of 2 units of unmanipulated cord blood. In patients in whom engraftment occurred, the median time to neutrophil engraftment was 15 days in the recipients of expanded cord blood, as compared with 24 days in controls who received unmanipulated cord blood only (P<0.001); the median time to platelet engraftment was 42 days and 49 days, respectively (P = 0.03). On day 26, the cumulative incidence of neutrophil engraftment was 88% with expansion versus 53% without expansion (P<0.001); on day 60, the cumulative incidence of platelet engraftment was 71% and 31%, respectively (P<0.001). CONCLUSIONS Transplantation of cord-blood cells expanded with mesenchymal stromal cells appeared to be safe and effective. Expanded cord blood in combination with unmanipulated cord blood significantly improved engraftment, as compared with unmanipulated cord blood only. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT00498316.)

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compared their outcomes with a control group (approximately 4:1) of patients who received MEL 200. Patients were matched for the year of transplant, chemosensitivity, disease status at auto-HCT and time from diagnosis to auto-HCT. Results: Preparative regimens were MEL 140 (19 patients), MEL180 (38 patients) and MEL 200 (253 patients). Patients in MEL 140 group were older (median age 70), with 58% patients older than 65 at auto-HCT (p 5 0.0001). Median serum creatinine level (1.71 mg/dl) was higher in the MEL 140 group (p 5 0.007). There was no significant difference in disease status (p 5 0.38) or chemosensitivity (p 5 0.28) between the 3 groups. Median times to neutrophil engraftment in MEL 140, 180 and 200 were 11, 10 and 10 days, respectively (p 5 0.15). Transplant-related mortality at 100 days was 0%, 2% and 0.8% in MEL 140, 180 and 200, respectively (p 5 1.0). Complete remission (CR) + very good partial remission (VGPR) were seen in 42%, 37% and 45% in Mel 140, 180 and 200, respectively (p 5 0.45). The overall response rate (CR + VGPR + PR) was 89%, 71% and 82% in MEL 140, 180 and 200, respectively (p 5 0.54). Median follow up in surviving patients in Mel 140, 180 and 200 was 13.8, 24.3 and 18.3 months, respectively. There was no significant difference in time to progression (p 5 0.27) between Mel 140, 180 or 200. Kaplan-Meier estimates of 2-year progression-free survival were 69%, 72% and 52% (p 5 0.74), and 2-year overall survival were 69%, 83% and 83% (p 5 0.48) in Mel 140, 180 and 200, respectively. Conclusion: The dose of melphalan can be safely reduced to 140 mg/m 2 in older patients or patients with renal insufficiency without adversely impacting the response rate, duration of remission or survival.

other management strategies. Associated increases in MAP, weight, and serum creatinine at the time of PRES compared to baseline measurements exemplify the importance of possible prevention through more aggressive blood pressure and fluid management strategies in this patient population.