Method of Combined Intermittent Hypoxia and Surface Muscle Electrostimulation for Enhancing Peripheral Stem Cells in Humans

Author(s):  
Ginés Viscor ◽  
Casimiro Javierre ◽  
Teresa Pagès ◽  
Luisa Corral ◽  
Joan Ramon Torrella ◽  
...  
1993 ◽  
Vol 2 (3) ◽  
pp. 351-355
Author(s):  
JOHN NEMUNAITIS ◽  
CRAIG ROSENFELD

Stem Cells ◽  
2015 ◽  
Vol 33 (2) ◽  
pp. 574-588 ◽  
Author(s):  
Marlen Weber ◽  
Galina Apostolova ◽  
Darius Widera ◽  
Michel Mittelbronn ◽  
Georg Dechant ◽  
...  

1996 ◽  
Vol 35 (sup7) ◽  
pp. 137-140 ◽  
Author(s):  
Thor Alvegård

Blood ◽  
1982 ◽  
Vol 59 (4) ◽  
pp. 822-827 ◽  
Author(s):  
LC Lasky ◽  
RC Ash ◽  
JH Kersey ◽  
ED Zanjani ◽  
J McCullough

Abstract Successful complete hematopoietic reconstitution (CHR) using nonleukemic peripheral stem cells (PSC) after marrow ablation has been reported in animals but not man. Previous studies of cytapheresis products from humans, as a prelude to use for CHR, have documented the presence of committed myeloid (CFU-GM) and erythroid (BFU-E) precursors. We have examined mononuclear cell (MNC) products collected on the Fenwal CS3000 Blood Cell Separator for these plus the more primitive mixed (granulo-, erythro-, mono-, and megakaryocytic) cell colony-forming units (CFU-GEMM) and for various lymphocytic subpopulations (LSP). One to two-hour products contained 36 +/- 7 CFU- GEMM/10(6) MNC (mean +/- SE, n = 8) or 490 +/- 131/ml product. This compared favorably with blood (23 +/- .4/10(6) MNC or 46 +/- 8/ml, n = 14) and bone marrow (146 +/- 58/10(6) MNC, n = 12). Collection efficiency for E-rosette-positive cells approximated that for total lymphocytes and was variable for other LSP. Recovery of CFU-GEMM after freezing in 10% dimethylsulfoxide at a controlled rate and storage in liquid N2 was 54% +/- 8% (n = 8). Cytapheresis collection of large numbers of pluripotent hematopoietic precursors and demonstration of adequate recovery of these after cryopreservation, both previously unreported, are significant steps toward eventual CHR using nonleukemic PSC.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2083-2083
Author(s):  
Brian Bolwell ◽  
Brad Pohlman ◽  
Matt Kalaycio ◽  
Steve Andresen ◽  
Elizabeth Kuczkowski ◽  
...  

Abstract Long-term results of conventional therapy of Hodgkin’s disease (HD) has demonstrated the importance of long-term and ongoing follow-up given the potential for later complications after curative therapy. While many transplant series report follow-up of several years after ABMT, few report a 15-year experience from a single institution. This report examines the outcomes of 220 patients receiving high-dose chemotherapy and autologous stem cell transplant (ABMT) at The Cleveland Clinic Foundation from January 1990 through June 2005. Median age was 33 years (range, 14–70 years); median time from diagnosis to transplant was 19 months; 47% received prior radiation therapy; 82% had nodular sclerosis histologic subtype; number of courses of prior chemotherapy were: 1 (16%), 2 (66%), 3 (14%), 4 or more (4%). All patients received salvage therapy prior to transplant: 29% were in a complete remission (CR), 55% in a partial remission (PR), and 16% refractory. All patients received a chemotherapy-only preparative regimen, most commonly Bu/Cy/VP (73%), followed by CBV (17%). 78% received peripheral stem cells alone; 22% received either autologous bone marrow or a combination of bone marrow plus peripheral stem cells. At the present time 60% of patients are alive. Of the 88 patients who died, the most common cause of death is relapse (69% of deaths). Secondary malignancy occurred in 11 patients (5%); 9 of these cases were secondary AML/MDS and 5 of these patients with secondary malignancies have died. 44% of the entire cohort has relapsed, at a median of 9 months post-transplant (range, 1.4–76 months). 10-year overall survival is 47%. A multivariable analysis showed that the two significant variables that correlated with post-BMT relapse were the number of prior chemotherapies (p = 0.011), and patients treated in remission vs. those not in remission (p = 0.002). Of patients receiving 2 or more prior courses of chemotherapy, 60% have relapsed 8 years post-transplant, compared to 40% of those receiving one course of prior chemotherapy. The risk of relapse by the number of prior chemotherapy courses is shown graphically below: Figure Figure In conclusion, this very large series of ABMT for recurrent HD with long-term follow-up demonstrates the importance of timely autografting in relapsed HD patients. The optimal time to proceed with ABMT is after failing one, and only one, course of chemotherapy. Delaying transplant for unrealistic long-term salvage with other courses of traditional chemotherapy will negatively affect the outcome of subsequent ABMT.


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4154-4154 ◽  
Author(s):  
Peter Lang ◽  
Tobias F. Feuchtinger ◽  
Patrick Schlegel ◽  
Heiko-Manuel Teltschik ◽  
Roland Meisel ◽  
...  

Abstract Abstract 4154 T and B cell depletion of haploidentical peripheral stem cells with CD3/CD19 coated magnetic microbeads prevents GvHD and allows to coinfuse large numbers of donor NK cells and other accessory cells. The anti CD3 specific OKT3 antibody was routinely used as rejection prophylaxis without affecting CD3 negative cells. However, due to its restricted availability, the substance had to be substituted by polyclonal ATG preparations with a longer half life period and comprising a broader variety of antigen, with the CD56 antigen in particular. We present data with reduced ATG doses given at the beginning of the conditioning regimen in order not to impair cotransfused NK cells and immune recovery. A total of 27 pediatric patients (ALL/AML n=9, relapsed solid tumors n=13, nonmalignant diseases n=5) received either 3×5 mg/kg (n=7) or 3×10 mg/kg (n=20) ATG-F (Fresenius) starting at day -12, followed by fludarabine (160 mg/m2, d -8 to -5) thiotepa (10 mg/m2 d -4) and melphalan (140 mg/m2 d −3 to −2). A median number of 14.4×106 CD34/kg and 62×106 NK cells/kg with 37×103 T cells/kg were infused. Median time to ANC>500 was 9 days in both groups. Graft rejection occurred in 3/7 patients with 15 mg ATG (42%) and in 2/20 patients with 30 mg ATG (10%). After reconditioning with a TLI based regimen, final engraftment was achieved in all patients. Acute GvHD grade II-IV was observed in 1/4 (15 mg) and 1/18 (6%, 30 mg) patients without rejection. Extensive chronic GvHD occurred in 1/4 (15 mg group) and 1/18 (30 mg group) patients. Immune recovery was monitored in the 30 mg group and compared with a historical group receiving OKT3 and the same chemotherapy (n=34). Recovery of CD56+ NK cells was fast with a mean number of 473 vs. 230 cells/μl at day +14, 299 vs. 281 cells/μl at day +30 and 245 vs. 236 cells/μl at day +90. CD3+ T cells reached 12 vs. 16/μl at day +30 and 138 vs. 217/μl at day +90 (30 mg group vs. OKT3 group; no significant differences for all data pairs). ATG serum levels were measured in 9 patients by flow cytometry (amount of ATG binding to the Jurkat cell line, defined as T cell specific rabbit IgG). Median peak levels of 10.5 μg/ml (15 mg group) and 15.0 μg/ml (30 mg group) specific rabbit IgG were reached between day -8 and -6 and dropped to 1.2 and 2.6 μg/ml at day 0. In vitro incubation of NK cells from healthy donors with a comparable dosage of ATG-F (1 or 10 μg/ml) resulted in 26 (41)% apoptosis and 0.2 (0.2)% necrosis (70 (52)% vital cells) after 24 hours. Conclusions: Our aim was to substitute OKT3 by ATG in patients who receive CD3/19 depleted haploidentical peripheral stem cells without hampering donor NK cells infused on day 0 and subsequent immune recovery. Administration of 15 or 30 mg/kg ATG-F was started at an early time point (day -12) of the regimen. Both doses resulted in low serum levels of specific ATG at day 0 and in a fast NK cell recovery. In vitro results suggested, that the majority of NK cells will not be damaged herewith. However, 15 mg/kg seemed to be not effective in preventing graft rejection and use of 30 mg/kg ATG-F has to be recommended. Immune recovery of T and NK cells was comparable to that of a historical control group who received OKT3. This approach will be also of interest for other transplantation strategies in which various components of the grafts and additionally given Tregs or specific T cells have to be preserved. Disclosures: Martinius: Fresenius Biotech: Employment.


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