Intra–bone marrow injection of bone marrow and cord blood cells: an alternative way of transplantation associated with a higher seeding efficiency

“…17,18 Comparable results have been shown with cord blood transplantation in the setting of allo-SCT. 19,20 Whether this approach will also reduce the replicative stress response in the auto-SCT setting requires further study.…”

Section: Discussionmentioning

confidence: 99%

Auto-SCT induces a phenotypic shift from CMP to GMP progenitors, reduces clonogenic potential and enhances in vitro and in vivo cycling activity defined by 18F-FLT PET scanning

Woolthuis

Agool

Olthof

et al. 2010

Bone Marrow Transplant

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Autologous SCT (auto-SCT) introduces a reduced tolerance to chemotherapy even in patients with adequate engraftment, suggesting long-term effects of the transplantation procedure on the BM capacity. To study the hematopoietic cell compartment after auto-SCT, CD34 þ BM cells (n ¼ 16) from patients at 6-9 months after auto-SCT were studied with regard to the progenitor subsets, colony frequency and cell cycle status. The BM compartments were studied in vivo using PET tracer 3-fluoro-3-deoxy-Lthymidine ( 18 F-FLT PET). BM CD34 þ cells after auto-SCT were compared with normal CD34 þ cells and showed a phenotypic shift from common myeloid progenitor (CMP mean percentage 3.7 vs 19.4%, P ¼ 0.001) to granulocytemacrophage progenitor (GMP mean percentage 51.8 vs 27.6%, P ¼ 0.01). In addition, a reduced clonogenic potential and higher cycling activity especially of the GMP fraction (41% ± 4 in G2/S phase vs 19% ± 2, P ¼ 0.03) were observed in BM after auto-SCT compared with normal. The enhanced cycling activity was confirmed in vivo by showing a significantly higher uptake of the 18 F-FLT PET tracer by the BM compartment. This study shows that auto-SCT results in defects of the hematopoietic compartment at least 6 months after auto-SCT, characterized by changes in the composition of progenitor subsets and enhanced in vitro and in vivo cycling activity.

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“…Using a nonobese diabetic/severe combined immunodeficiency (NOD/SCID) xenotransplant model for studying the engraftment of human rapid short-term SCID repopulating cells (R-SRC), McKenzie et al 1 demonstrated higher engraftment 2 and 6 weeks after transplanting Lin À CD34 þ CD38 þ /lo cells from human UCB by direct intrafemoral injection compared with the usual intravenous (IV) route. 1 Earlier Castello et al 2 demonstrated that intraosseous (IO) transplantation of UCB mononuclear cells was associated with a seeding efficiency 15 times greater than IV transplantation. 2 Based on their findings in mice and monkey models, Ikehara et al 3 considered intra-bone marrow (BM) transplantation a potentially important strategy.…”

mentioning

confidence: 99%

“…1 Earlier Castello et al 2 demonstrated that intraosseous (IO) transplantation of UCB mononuclear cells was associated with a seeding efficiency 15 times greater than IV transplantation. 2 Based on their findings in mice and monkey models, Ikehara et al 3 considered intra-bone marrow (BM) transplantation a potentially important strategy.…”

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confidence: 99%

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confidence: 99%

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Can intra-osseous transplantation improve results of umbilical cord blood transplantation in adult patients?

Zaidi¹,

Sahovic²,

Alshanqeeti³

et al. 2005

Bone Marrow Transplant

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Some recently published studies [1][2][3] have raised intriguing questions which may be clinically relevant for future clinical trials of umbilical cord blood (UCB) transplantation in adults. Using a nonobese diabetic/severe combined immunodeficiency (NOD/SCID) xenotransplant model for studying the engraftment of human rapid short-term SCID repopulating cells (R-SRC), McKenzie et al. 1 demonstrated higher engraftment 2 and 6 weeks after transplanting Lin À CD34 þ CD38 þ /lo cells from human UCB by direct intrafemoral injection compared with the usual intravenous (IV) route. 1 Earlier Castello et al. 2 demonstrated that intraosseous (IO) transplantation of UCB mononuclear cells was associated with a seeding efficiency 15 times greater than IV transplantation. 2 Based on their findings in mice and monkey models, Ikehara et al. 3 considered intra-bone marrow (BM) transplantation a potentially important strategy.The concept of using the IO route of infusion in emergencies is re-emerging 4 and its safety is well established. 5 In addition to IO needles and BM biopsy needles, semiautomated devices are being evaluated for this purpose. The IO route of BM transplantation, using posterior iliac crests, has already been tested successfully in a prospective randomized fashion both in children 6 and adults. 7 Although engraftment was not faster, a significant reduction in the number of days on total parenteral nutrition and a tendency toward a reduction in the number of days on antibiotics was noted in the IO compared with the IV group. 7 Interestingly bacteremia did not occur in the IO group. 7 Major obstacles in the success of UCB transplantation in adult patients include relatively smaller dose of stem cells in the graft and delayed engraftment leading to high infectious morbidity and mortality. 8 In spite of being a rich source for CD34 þ CD38 À stem cells and R-SRC, 9 some of the repopulating cells in UCB may have significantly reduced homing levels when injected IV. 1,10 McKenzie et al. 1 showed that anti-CD122 antibody was useful in overcoming CD122 þ cell-related resistance in this xenotransplantation model, and also pointed out that faster and better engraftment in IO transplantation as compared with usual IV transplantation might be related to host resistance factors other than CD122 þ cells, preventing the homing of UCB R-SRC to appropriate hematopoetic niches within the BM. 1 Now, with the availability of a variety of growth factors, and the strategies of multiunit UCB transplantation and ex vivo expansion of UCB units being explored in studies, 8 the time may be right for testing the approach of IO transplantation of UCB as a way of overcoming the problem of delayed engraftment. We propose that this strategy be tested prospectively to compare IO route, IV route and combined IV and IO route using single or multiple UCB units.

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Intra–bone marrow injection of bone marrow and cord blood cells: an alternative way of transplantation associated with a higher seeding efficiency

Cited by 79 publications

References 27 publications

Twenty-year follow-up of a randomized trial comparing intraosseous and i.v. BM transplantation

Twenty-year follow-up of a randomized trial comparing intraosseous and i.v. BM transplantation

Auto-SCT induces a phenotypic shift from CMP to GMP progenitors, reduces clonogenic potential and enhances in vitro and in vivo cycling activity defined by 18F-FLT PET scanning

Can intra-osseous transplantation improve results of umbilical cord blood transplantation in adult patients?

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