scholarly journals Phase I clinical trial of intra‐bone marrow cotransplantation of mesenchymal stem cells in cord blood transplantation

Author(s):  
Tatsunori Goto ◽  
Makoto Murata ◽  
Tetsuya Nishida ◽  
Seitaro Terakura ◽  
Sonoko Kamoshita ◽  
...  
Medicine ◽  
2018 ◽  
Vol 97 (17) ◽  
pp. e0449 ◽  
Author(s):  
Tatsunori Goto ◽  
Makoto Murata ◽  
Seitaro Terakura ◽  
Tetsuya Nishida ◽  
Yoshiya Adachi ◽  
...  

Blood ◽  
2003 ◽  
Vol 102 (3) ◽  
pp. 1138-1141 ◽  
Author(s):  
Francesco Frassoni ◽  
Marina Podestà ◽  
Rita Maccario ◽  
Giovanna Giorgiani ◽  
Gabriele Rossi ◽  
...  

Abstract Delayed hematopoietic recovery is the main factor precluding a wider use of cord blood (CB) transplants. We hypothesized that this delayed engraftment might not be related to an insufficient number of stem cells in the graft, but to an intrinsic difficulty of these cells to undergo differentiation. To test our hypothesis, 2 groups of children were compared; 12 received a CB transplant and 12 an adult bone marrow (BM) transplant. We studied neutrophil and platelet recovery and, at a median time of approximately 1 year after transplantation, the frequency of colony-forming cells (CFCs) and long-term culture initiating cells (LTC-ICs) in the BM of the 2 groups. Recipients of BM transplants received 1-log more cells and had significantly faster neutrophil and platelet recovery. Conversely, the frequency of committed and early progenitors was significantly higher in the BM of children given CB cells compared with BM transplant recipients (median count of CFC/2 × 104 BM mononuclear cells, 20 versus 11, P = .007; median count of LTC-IC/106 BM mononuclear cells, 8.2 versus 0.2 P = .001). CB, but not adult BM stem cells, can better restore the host hematopoietic progenitor cell reservoir; the delayed engraftment after CB transplantation may reflect the difficulty of CB progenitors to reprogram themselves toward differentiation.


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5189-5189
Author(s):  
Koichiro Yuji ◽  
Shigesaburo Miyakoshi ◽  
Tomohiro Myojo ◽  
Yuji Miura ◽  
Daisuke Kato ◽  
...  

Abstract [Background] Non-myeloablative regimens have been proven to allow engraftment following allogeneic stem cells transplantation with minimal procedure-related toxicity and lower costs. Cord blood has emerged as an appealing alternative source of hematopoietic stem cells for unrelated donor transplantation, but delayed engraftment and frequent transfusion were reported. No studies have formally evaluated the cost of reduced-intensity cord blood transplantation (RICBT). [Purpose] To evaluate the relationship among costs, baseline patient characteristics, and major complications of RICBT, we performed an economic analysis of data in a clinical trial of RICBT for hematologic diseases at a single institution. [Patients and Methods] Ninety-three patients with hematological diseases (median age, 55y; range, 17–79: median body weight, 53kg; range, 38–75) underwent RICBT from March 2002 to May 2004 in Toranomon Hospital. Mean follow-up period was 77 days (range, 13–863). Data on resource use, including hospitalizations, medical procedures, medications, and diagnostic tests, were abstracted from subjects’ clinical trial records. Resources were valued using the Japanese national insurance reimbursement system for inpatient costs at one hospital and average wholesale prices for medications. Monthly costs were calculated and stratified by treatment group and clinical phase. [Results] The median initial inpatient cost was $80,400 (range, 41,300–154,700). When baseline variables were considered, disease status was significant predictor of costs. When clinical events were considered, in-hospital death was associated with higher costs. The mean length of total inpatient days was 78 days (range, 31–222), and the mean length of inpatient days post transplant was 51 days (range, 15–131). The mean units of transfused RBC, Platelet, and FFP were 27u, 224u, and 27u, respectively. [Discussion] This study firstly demonstrates that the cost of RICBT was much higher as compared to previous RIST using peripheral blood or bone marrow. RICBT is an attractive therapy, however, economic problem lies before prevalence of RICBT. The increased numbers of transfusions and supportive care would have effects on costs. The association between mortality and higher costs suggest that prevention of clinical complication may have significant economic benefits. Interventions that decrease these complications may have favorable cost-benefit ratios, and will be the focus of future investigation.


2013 ◽  
Vol 22 (11) ◽  
pp. 2041-2051 ◽  
Author(s):  
Kang-Hsi Wu ◽  
Chris Tsai ◽  
Han-Ping Wu ◽  
Martin Sieber ◽  
Ching-Tien Peng ◽  
...  

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1199-1199
Author(s):  
Alma J. Nauta ◽  
Alwine B. Kruisselbrink ◽  
Roelof Willemze ◽  
Willem E. Fibbe

Abstract Umbilical cord blood (UCB) is considered as an attractive alternative source of hematopoietic stem cells for allogeneic stem cell transplantations in patients who lack HLA-matched donors. However, the low cell dose adversely affects the speed of hematopoietic recovery and therefore limits the application of UCB transplantation in adults. Although ex-vivo expansion of cord blood cells has been explored as a strategy to increase the cell dose, compromised engraftment potential of expanded cells has been demonstrated. Another approach to overcome cell dose limitations is transplantation of multiple, unrelated UCB units. To investigate the effect of multiple cord transplantation on engraftment, NOD/SCID mice were transplanted with human hematopoietic progenitor cells (CD34+) derived from two UCB units with HLA disparity. During the first six weeks after transplantation the number of human platelets in peripheral blood was quantified by flow cytometry. Six weeks after transplantation, the mice were sacrificed and the percentage and donor origin of human CD45+ cells in blood, and in bone marrow was determined by flow cytometry. Transplantation of CD34+ cells derived from two UCB donors resulted in significantly higher number of human platelets in peripheral blood than transplantation of CD34+ cells from either donor alone, ranging from 3.92x106/ml to 10.29x106/ml (mean 6.4x106 ± 2.55x106/ml) and 0.11x106/ml to 3.12.106/ml (mean 1.42x106 ± 1.17x106/ml), respectively. Furthermore, the overall human cell engraftment level in bone marrow after double cord blood transplantation ranged from 7.01% to 64.34% (mean 29.6 ± 21.5%) a nearly 7-fold increase compared to single cord blood transplantation ranging from 0.27% to 13.5% (mean 4.6 ± 3.8%) Although consistently higher engraftment levels were reached after double cord blood transplantation, two different patterns were observed: in 2 out of 4 experiments cells from one donor predominated the engraftment (ratio 3:1), while in two other experiments the two units contributed equally to BM engraftment. The mechanism underlying these effects are <S>is</S> not yet clear. It is not very likely that the single donor predominance results from an unequal amount of hematopoietic stem cells in the cord blood units because each cord blood showed comparable levels of engraftment as a single unit. Alternatively, the unequal engraftment may result from an immunological competition or a graft versus graft stimulatory effect between the cords during the engraftment process and further studies are required to determine if the contribution of both units is dependent on the degree of HLA matching between the two cords. Taken together, these results demonstrate that double cord blood transplantation may represent a means of achieving increased engraftment, making multiple cord blood transplantation a promising strategy to improve the outcome of UCB transplantation. Studies are underway to unravel the mechanisms underlying the enhanced engraftment.


2013 ◽  
Vol 95 (5) ◽  
pp. 773-777 ◽  
Author(s):  
Kang-Hsi Wu ◽  
Ji-Nan Sheu ◽  
Han-Ping Wu ◽  
Chris Tsai ◽  
Martin Sieber ◽  
...  

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