scholarly journals Infusion of Non-HLA Matched, Off-the-Shelf Ex Vivo Expanded Cord Blood Progenitor Cells in Patients Undergoing Myeloablative Cord Blood Transplantation Is Safe and Decreases the Time to Neutrophil Recovery

2012 ◽  
Vol 18 (2) ◽  
pp. S203 ◽  
Author(s):  
C. Delaney ◽  
F. Milano ◽  
H. Shelly ◽  
I. Nicoud ◽  
I.D. Bernstein
Keyword(s):  
Cord Blood ◽  
Progenitor Cells ◽  
Ex Vivo ◽  
Cord Blood Transplantation ◽  
Neutrophil Recovery ◽  
Blood Transplantation

Notch-Mediated Expansion of Human Cord Blood Progenitor Cells Results in Rapid Myeloid Reconstitution in Vivo Following Myeloablative Cord Blood Transplantation

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 212-212 ◽  
Author(s):  
Colleen Delaney ◽  
Carolyn Brashem- Stein ◽  
Howard Voorhies ◽  
Jonathan Gutman ◽  
Mari Dallas ◽  
...  
Keyword(s):  
Cord Blood ◽  
Progenitor Cells ◽  
Cultured Cells ◽  
Ex Vivo ◽  
Cord Blood Transplantation ◽  
Fold Increase ◽  
Short Term ◽  
Post Transplant ◽  
Blood Transplantation ◽  
Cell Fractions

Abstract Delayed hematopoietic recovery following cord blood transplantation (CBT) is thought to result from inadequate numbers of progenitor cells in the graft and is associated with increased early transplant related morbidity and mortality. Using an engineered form of the Notch ligand, Delta1, we have previously reported on novel ex vivo expansion methods for generating greatly increased numbers of human CD34 progenitor cells that repopulate immunodeficient mice with markedly enhanced rate and magnitude. We now report results of the initial 6 patients enrolled in a phase I study evaluating the safety and potential efficacy of cord blood (CB) progenitors cultured in the presence Delta1 and recombinant cytokines, with the goal of generating increased numbers of short term repopulating cells capable of providing rapid myeloid engraftment. These patients (AML, n=5; bi-phenotypic leukemia, n=1), were treated with a myeloablative preparative regimen consists of cytoxan 120mg/kg, fludarabine 75mg/m2 and 1320 cGy TBI, followed one day later by infusion of one non-cultured CB unit and then a second unit that has been CD34 enriched and cultured for 16 days as previously described. The median age and weight of the patients enrolled is 28 years (range 11 to 43) and 61.5 kilograms (range 26 to 76). CB units were selected on the basis of cell dose and a requirement of matching at least 4 of 6 loci with the patient (intermediate resolution for HLA-A and B, and high resolution for HLA-DRB1). The non-cultured unit in all patients was 4/6 matched to the patient. The unit used for expansion was 5/6 matched to the patient in two cases, and 4/6 matched in the other four. After culture, there was an average CD34 fold increase of 160 (range 41 to 382) with an average total nucleated cell (TNC) fold increase of 660 (range 146 to 1496). Average infused TNC/kg x107 was 2.9 (range 1.9–5.8) and 4.6 (range 0.6–9.1) for the non-cultured and cultured cells respectively, and infused CD34 cells/kg (x105) was 2.2 (range 1.1–3.4) and 53.4 (range 9.3–133) respectively. No T cells were generated during culture and no toxicities directly attributable to the cultured product, including infusional or increased acute GVHD, have been observed. All patients have engrafted. Relatively rapid engraftment was observed in 5 out of 6 patients treated to date, with a median time to engraftment of 14 days (range 7 to 34), as compared to 25 days (range 16 to 48) in patients (n=17) undergoing an identical transplant regimen at this center, but with 2 non-cultured CB units. The relative contribution of the expanded and non-cultured grafts over time was determined by a DNA-based assay for short tandem repeat loci on peripheral blood sorted cell fractions to include CD3+, CD33+, CD56+, CD14+ and CD19+ cells, beginning day +7 post transplant. In the 5 patients with early myeloid engraftment (≤20 days), engrafted myeloid cells present at day 7 were derived almost entirely from the expanded unit. In three of these five, ANC >500 was observed at days 7, 9 and 16 and was mainly derived from the expanded unit, whereas in the other 2 patients who achieved ANC>500 at day 13 and 20, myeloid engraftment at day 14 was derived from the non-cultured cells. Persistent contribution to engraftment from the expanded cells has been noted in two patients, one through 280 days post transplant but no longer present at one year, and in a more recently treated patient who is currently 75 days post transplant, the expanded cells continue to dominate in CD33, CD14 and CD56, but not CD3, sorted cell fractions. Furthermore, time to platelet engraftment (>20k) has averaged 30 days (range 19–53). Average follow-up time is 277 days (range 70–632). One patient died on day 462 from complications of VZV myelitis; all other patients are alive and in remission. Overall, accelerated myeloid engraftment has been observed in 5/6 patients treated to date as a direct result of Notch-mediated ex vivo expansion of one of two CB units prior to transplantation with ultimate engraftment from the T replete non-cultured unit. These results further suggest that improvement in early myeloid reconstitution may result from provision of short term repopulating cells and/or of cells able to facilitate engraftment of the non-cultured unit. These studies continue with the goal of achieving consistent, rapid engraftment in recipients of hematopoietic cell transplants to decrease morbidity and mortality in the early post-transplant setting.

Cost-Effectiveness of Double-Unit Cord Blood Transplantation Versus Single-Unit Cord Blood Transplantation in Adult Patients with Acute Leukaemia in France- On Behalf of SFGM-TC, Eurocord, ALWP-EBMT

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3130-3130
Author(s):  
Myriam Labopin ◽  
Annalisa Ruggeri ◽  
Namik Taright ◽  
Federico Garnier ◽  
Catherine Faucher ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Cord Blood ◽  
Median Time ◽  
Acute Leukaemia ◽  
Acute Gvhd ◽  
Cord Blood Transplantation ◽  
Neutrophil Recovery ◽  
Blood Transplantation ◽  
The Cost ◽  
Mean Cost

Abstract Abstract 3130 Unrelated donor cord blood transplantation (UCBT) using a single (s) or double (d) CB unit has become a widely accepted treatment for hematologic diseases in the absence of an HLA identical stem cell donor. Retrospective studies have reported a reduced risk of relapse after dUCBT compared with sUCBT, however one limitation of using dUCBT is the cost of the 2 units, but comparison of the total cost of the 2 procedures has not yet been published. The aim of this study was to evaluate the outcome of adult patients transplanted for acute leukaemia in first remission and to access the cost-effectiveness of dUCBT compared to sUCBT). We analyzed clinical results and costs of 134 consecutive CBT performed in 31 transplant centers in France from 2001 to 2009. All hospital costs were estimated from donor search to 1 year after UCBT, according to the French public system. A Markov decision analysis model was used to calculate the QALY (quality-adjusted life years) and cost-effectiveness ratio (ICER). For cost-effectiveness analysis, reduced intensity conditioning (RIC) and myeloablative conditioning (MAC) were studied separately. Forty patients were transplanted for ALL and 94 for AML in CR1. Median age was 42 years and median time from diagnosis to UCBT was 180 days. CMV serology for 49% of patients was negative. Sixty one patients received a sUCBT and 73 a dUCBT. Twenty eight percent of CB units were HLA identical to recipient or had 1 HLA disparity (antigen level for HLA-A and B allelic level for DRB1) and 72% had 2–3 HLA disparities. Median infused nucleated cell dose was 2.7×107/kg in sUCBT and 3.8×107/kg in dUCBT. Seventy nine patients received a RIC (97% TBI<4Gy based) and 55 a MAC (84% TBI ≥4Gy Based). The median follow-up was 31 months after sUCBT and 24 months after dUCBT. Neutrophil recovery was achieved in 115 patients (51 of 61 patients who received a sUCBT and 64 of 73 dUCBT), with a median time of 23 (6–53) days. No statistical difference was observed for neutrophil recovery after sUCBT or dUCBT. dUCBT was associated with a higher rate of acute GVHD grade II-IV: 56% versus 30% for sUCBT, p=0.003. At day +100, 53% of patients experienced CMV reactivation (37% after sUCBT and 71% after dUCBT, p=0.01), 45% had viral infection other than CMV and 49% had bacterial infection. Fifteen patients (11%) received a second transplant, 6 for graft failure (4 in sUCBT group and 2 in dUCBT group) and 9 for relapse (6 in sUCBT group and 3 in dUCBT group). The median interval between first and second transplant was 327 days. The estimated survival at 2 years was 40±6% vs 58±6% after sUCBT and dUCBT, respectively (p=0.04). Leukaemia-free survival at 2 years was 30±6% in sUCBT vs 49±6% in dUCBT, (p=0.09). Cumulative incidence of relapse at 2 years was lower after dUCBT: 29±4% vs to 42±4% after sUCBT, (p=0.04). No statistically significant difference was observed in terms of non-relapse mortality and incidence of chronic GVHD. The mean cost for donor identification and UCB acquisition was 28.164 € for sUCBT and 48.929 € for dUCBT. The estimated costs within 1 year after RIC-sUCBT was 133.790 € and it was 211.735 € after MAC-sUCBT. The estimated cost was 180.549 € after RIC-dUCBT and 205.375 €, after MAC-dUCBT. Table 1 summarizes details of costs by type of graft and conditioning. In the MAC group, dUCBT was associated with lower cost (minus 13.554€) and better effectiveness (plus 0, 53 QALY). The cost per QALY obtained after RIC-dUCBT compared with sUCBT was 91.199 €. In conclusion, In France, dUCBT is associated with higher incidence of acute GVHD, lower relapse and better survival in adults transplanted for acute leukaemia. With a MAC, dUCBT is the best option, and the cost per QALY obtained for dUCBT when using RIC is acceptable.Table.Estimated costs from donor search to 1 year after transplantation for single UCBT, double UCBT and type of conditioning regimen (MAC or RIC)sUCBTdUCBTCB unit search28 164 €48 929 €MACInitial hospitalisationMean duration (d)6665Mean cost137.757 €131.773 €Outpatient visitsNumber of days911Mean cost7.788 €9.223 €Further hospitalisationsMean duration (d)5023Mean cost38.026 €15.449 €Total mean cost within 1 year211.735 €205.374 €RICInitial hospitalisationMean duration (d)2948Mean cost58.621 €96.335 €Outpatient visitsNumber of days2123Mean cost17.870 €19.366 €Further hospitalisationsMean duration (d)4021Mean cost29.135 €15.918 €Total mean cost within 1 year133.790 €180.549 € Disclosures: No relevant conflicts of interest to declare.

scholarly journals Human Application of Ex Vivo Expanded Umbilical Cord-Derived Mesenchymal Stem Cells: Enhance Hematopoiesis after Cord Blood Transplantation

2013 ◽  
Vol 22 (11) ◽  
pp. 2041-2051 ◽  
Author(s):  
Kang-Hsi Wu ◽  
Chris Tsai ◽  
Han-Ping Wu ◽  
Martin Sieber ◽  
Ching-Tien Peng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cord Blood ◽  
Umbilical Cord ◽  
Ex Vivo ◽  
Cord Blood Transplantation ◽  
Blood Transplantation

scholarly journals Proteomic Profiling ofEx VivoExpanded CD34-Positive Haematopoetic Cells Derived from Umbilical Cord Blood

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Heiner Falkenberg ◽  
Teja Falk Radke ◽  
Gesine Kögler ◽  
Kai Stühler
Keyword(s):  
Cord Blood ◽  
Ex Vivo ◽  
Protein Biosynthesis ◽  
Protein Profile ◽  
Cord Blood Transplantation ◽  
Enrichment Analysis ◽  
Proteomic Profiling ◽  
Blood Transplantation ◽  
Proteome Level ◽  
Proteomic Change

Ex vivoexpansion of haematopoetic cells by application of specific cytokines is one approach to overcome boundaries in cord blood transplantation due to limited numbers of haematopoetic stem cells. While many protocols describe an effective increase of total cell numbers and the amount of CD34-positive cells, it still remains unclear if and how the procedure actually affects the cells’ properties. In the presented publications, CD34-positive cells were isolated from cord blood and expanded for up to 7 days in media supplemented with stem cell factor (SCF), thrombopoietin (THPO), interleukin 6 (IL-6), and fms-related tyrosine kinase 3 ligand (FLT3lg). At days 3 and 7, expanded cells were harvested and analyzed by flow cytometry and quantitative proteomics. 2970 proteins were identified, whereof proteomic analysis showed 440 proteins significantly changed in abundance duringex vivoexpansion. Despite the fact that haematopoetic cells still expressed CD34 on the surface after 3 days, major changes in regard to the protein profile were observed, while further expansion showed less effect on the proteome level. Enrichment analysis of biological processes clearly showed a proteomic change toward a protein biosynthesis phenotype already within the first three days of expression.

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