scholarly journals Allogeneic Umbilical Cord Blood Infusion for Adults with Ischemic Stroke (CoBIS): Clinical Outcomes From a Phase 1 Study

2017 ◽  
Vol 23 (3) ◽  
pp. S173-S174 ◽  
Author(s):  
Joanne Kurtzberg ◽  
Jesse D. Troy ◽  
Ellen Bennett ◽  
Rebecca Durham ◽  
Elizabeth J. Shpall ◽  
...  
Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2284-2284 ◽  
Author(s):  
Joanne Kurtzberg ◽  
Jesse D Troy ◽  
Ellen Bennett ◽  
Samir Belagaje ◽  
Elizabeth J. Shpall ◽  
...  

Abstract Background: Over 750,000 patients/year in the US experience a debilitating stroke. Approximately 88% of adult strokes are ischemic in etiology, and occur when cerebral blood flow is blocked by a clot or mechanical event. To date, there are no effective therapies. The initial neuroinflammatory response following stroke results in the release of inflammatory mediators which may exacerbate the development of cerebral edema and secondary tissue injury. Preclinical data suggest that cell-based therapy may favorably alter the natural history of these processes through paracrine signaling that reduces inflammation, promotes angiogenesis, neurogenesis and recruitment of endogenous cell repair mechanisms. We hypothesize that intravenous infusion of banked non-HLA matched allogeneic umbilical cord blood (UCB) is safe and will, through tropic effects, improve functional outcome in patients with acute ischemic stroke. Methods: The CoBIS study (NCT02397018) is a prospective, open-label, multi-center, Phase 1 safety study of a single intravenous infusion of allogeneic UCB in patients with ischemic stroke. Adult patients experiencing a recent, acute cortical ischemic stroke in the middle cerebral artery (MCA) with a National Institutes of Health Stroke Scale (NIHSS) score of 8-15(right hemisphere) or 8-18 (left hemisphere) were eligible for enrollment. Cord blood units were selected to match for ABO/Rh and race but not for HLA. Subjects were not pre-treated with immunosuppressive drugs and infused with cell product 3-9 days post stroke. The primary endpoint was safety as assessed by the frequency and severity of adverse events occurring within 24 hours of cord blood infusion within a 12-month period post-infusion. Secondary outcome measures to assess physical and neurological function included modified Rankin Scale (mRS), NIHSS, and Barthel Index (BI). Results: Ten male patients with a mean age of 61.5 years (range 45-79) were enrolled between July 2015 and February 2016 at Duke University and Houston Methodist Hospital. All subjects were independent prior to the stroke; 9 subjects had an historic mRS of 0 and one subject had an historic mRS of 1 due to bilateral below the knee amputation. Study participants received an intravenous infusion of 0.83-3.34 X 10e7 TNC/kg administered between 3-9 days post stroke. At time of infusion (baseline), the mean mRS was 4.4±0.5 (range 4-5). At 3 months, the mean mRS was 2.8±0.9 (range 2-4) and 50% of subjects exhibited a 1 grade increase (improvement) in mRS, 40% had improved by 2 grades and one subject by 3 grades. According to studies examining change in mRS over time, 58% of patients disabled by stroke (mRS 3-5) will improve by at least one grade by 3 months (Kelly-Hayes et al, J. Neurol Rehab 1989). The mean NIHSS at the time of enrollment was 13.6±0.8 (range 12-15), at infusion (baseline) 11.2 ±1.6 (range 9-14), and at 3 months 5.3±2.2 (range 3-9) with a shift down (improvement) by at least 4 points (mean 6.1±1.7; range 4-9) relative to baseline. Similarly, all patients showed improvement in basic activities of daily living at 3 months relative to infusion (baseline), as measured by the BI (mean 52.0±24.7; range 10-80). As of June, 2016, four serious AEs were observed in one study subject but were unrelated to study therapy and not reportable. Conclusions: Six month safety data suggests intravenous infusion of unmatched, allogeneic, UCB cells is feasible and well tolerated in adult patients with acute ischemic stroke. Furthermore, all patients exhibited improved functional outcomes at 3 months relative to baseline as measured by mRS, NIHSS and BI. These results should be further investigated in a controlled and randomized Phase 2 study using human UCB and placebo in patients with ischemic stroke which is planned to begin Q4 2016. Disclosures No relevant conflicts of interest to declare.


2018 ◽  
Vol 7 (7) ◽  
pp. 521-529 ◽  
Author(s):  
Daniel T. Laskowitz ◽  
Ellen R. Bennett ◽  
Rebecca J. Durham ◽  
John J. Volpi ◽  
Jonathan R. Wiese ◽  
...  

Blood ◽  
2003 ◽  
Vol 101 (12) ◽  
pp. 5061-5067 ◽  
Author(s):  
Jennifer Jaroscak ◽  
Kristin Goltry ◽  
Alan Smith ◽  
Barbara Waters-Pick ◽  
Paul L. Martin ◽  
...  

AbstractAllogeneic stem cell transplantation with umbilical cord blood (UCB) cells is limited by the cell dose a single unit provides recipients. Ex vivo expansion is one strategy to increase the number of cells available for transplantation. Aastrom Biosciences developed an automated continuous perfusion culture device for expansion of hematopoietic stem cells (HSCs). Cells are expanded in media supplemented with fetal bovine serum, horse serum, PIXY321, flt-3 ligand, and erythropoietin. We performed a phase 1 trial augmenting conventional UCB transplants with ex vivo–expanded cells. The 28 patients were enrolled on the trial between October 8, 1997 and September 30, 1998. UCB cells were expanded in the device, then administered as a boost to the conventional graft on posttransplantation day 12. While expansion of total cells and colony-forming units (CFUs) occurred in all cases, the magnitude of expansion varied considerably. The median fold increase was 2.4 (range, 1.0-8.5) in nucleated cells, 82 (range, 4.6-266.4) in CFU granulocyte-macrophages, and 0.5 (range, 0.09-2.45) in CD34+ lineage negative (lin–) cells. CD3+ cells did not expand under these conditions. Clinical-scale ex vivo expansion of UCB is feasible, and the administration of ex vivo–expanded cells is well tolerated. Augmentation of UCB transplants with ex vivo–expanded cells did not alter the time to myeloid, erythroid, or platelet engraftment in 21 evaluable patients. Recipients of ex vivo–expanded cells continue to have durable engraftment with a median follow-up of 47 months (range, 41-51 months). A randomized phase 2 study will determine whether augmenting UCB transplants with ex vivo–expanded UCB cells is beneficial.


2018 ◽  
Vol 24 (3) ◽  
pp. S206-S207
Author(s):  
Troy C. Quigg ◽  
Sherri Shade ◽  
Candace Taylor ◽  
Cody Ginn ◽  
Juan Huerta ◽  
...  

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 967-967
Author(s):  
Guillermo López-González ◽  
Charles F. LeMaistre ◽  
Carlos Bachier ◽  
Brad Smith ◽  
Ka Wah Chan ◽  
...  

Abstract Umbilical cord blood (UCB) is a viable source of hematopoietic stem cells (HSC) however, because of the increased risk of nonengraftment associated with low total nucleated cell counts (TNC) per kg, double UCB (DCB) transplants are used in larger patients (pts). Minimal data has been collected on cost analysis and clinical outcomes comparing DCB to peripheral blood (PB) and bone marrow (BM) unrelated donor (UD) transplants. Thus, we conducted a retrospective review of DCB transplants (n=30) from January 2004 through April 2008 compared to BM (n= 23, 30%) and PB (n = 54, 70%) UD transplants during the same time period. Median age was 21 yrs (range 13–66) for DCB recipients and 45 yrs (range 0.4–67) for UD pts. UD pts were HLA typed at A, B, C, DR, and DQ and matched with donors at 9(10) (21%) and 10(10) (79%) loci [all mismatches at class I alleles]. Pts were considered for DCB transplant if a suitable 10/10 or 9/10 donor could not be identified. DCB recipients had HLA matches of 6/6, 5/6/, 4/6 and 3/6 as follows: (cord 1/ cord 2): (0.0%/6.7%), (20.0%/30.0%), (76.7%/63.3%), (3.3%/0.0%) [HLA disparity between each UCB unit and recipient was not necessarily at the same loci]. The median TNC/kg in DCB pts was 2.03x107 (range 7.9x106 – 9.3x108). Full intensity preparative regimens (BuCY2 or TBI³ 1200 cGy based) were used in 43% of UD and 50% of DCB pts. Median day to ANC>500/ul for DCB and UD pts was 23 days (range 6–66) and 15 days (range 7–52), and platelet >20,000/ul was 52 days (range 7–130) and 19 days (range 9–63), respectively. Incidences of acute GVHD ≥2 and chronic GVHD in the UD and DCB pts were 61.0% and 51% vs. 53.3% and 45%, respectively. Median follow-up was 143 days (range 12–847) for the DCB group and 242 days (range 34–1506) for the UD pts. Estimated overall survival (OS) at 1 year was 61% (95% CI: 48% to 71%) for UD pts vs. 55% (95% CI: 34% to 72%) in DCB pts (p = NS). Estimated transplant related mortality (TRM) at 100 days for UD pt was 6.5% (95% CI: 2.8% to 14.9%) and 16.7% (95% CI: 7.3% to 35.5%) (p=0.09) in DCB pts. There were 48 total deaths; 14 (46.7%) in the DCB pts and 34 (44.2%) in the UD pts. In both the DCB and UD groups, disease relapse (21.4% and 23.5%) and infection (28.6% and 14.7%) caused the majority of deaths. All facility transplant related costs were reviewed from the transplant center thru the first year post transplant, excluding pretransplant workup and care not received at the transplant center. The total median costs for DCB transplants were significantly more than the UD costs at D30, D100 and 1yr post transplant by differences of $42,067, $50,806, and $52,297, respectively (p<0.05 for each time interval). The median length of stay for initial hospitalization at start of preparative regimen was 22 days (2–144) in the UD pts and 29 days (6–103) in the DCB pts, and 60% of total median costs occurred by D30 in the DCB group compared to 52% in the UD group. In conclusion, DCB provides a viable option for HSC with comparable clinical outcomes to UD transplants, however DCB transplants are more expensive primarily because of inpatient costs in the first 30 days.


2016 ◽  
Vol 22 (3) ◽  
pp. S385-S386
Author(s):  
Troy C. Quigg ◽  
Candace Taylor ◽  
Juan Huerta ◽  
Alfred Nanez ◽  
Robert Sanders ◽  
...  

Cytotherapy ◽  
2010 ◽  
Vol 12 (6) ◽  
pp. 713-720 ◽  
Author(s):  
Patrick J. Hanley ◽  
Conrad Russell Cruz ◽  
Elizabeth J. Shpall ◽  
Catherine M. Bollard

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