G-CSF in Healthy Allogeneic Stem Cell Donors

Hölig, Kristina

doi:10.1159/000354196

Cited by 60 publications

(65 citation statements)

References 64 publications

(81 reference statements)

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“…Mobilization of PBSC with G-CSF and leukapheresis has become a well-established procedure worldwide and is the main technique for the procurement of allogeneic hematopoietic stem cell transplants [7]. HLA-compatible sibling donors have traditionally been considered the optimal hematopoeitic stem cell donor because of their immediate availability and superior outcomes of the transplant compared to unrelated donors [6].…”

Section: Discussionmentioning

confidence: 99%

“…A G-CSF dose between 10 μg/kg to 16 μg/kg G-CSF is accepted as a standard and used by most centres worldwide [7,21].…”

Section: Discussionmentioning

confidence: 99%

“…The optimal dose of G-CSF for mobilization of PBSCs has been extensively discussed [7] and various doses have been used ranging from 3 to 20 μg/kg/day [7]. Higher PBSC CD34+ yields per recipient weight are linked to faster hematopoietic engraftment and better transplant outcome [8,9].…”

mentioning

confidence: 99%

“…Many clinical parameters with possible impact on the yield of PBSCs including comorbidities, gender, race, donor weight, age, pre-apheresis peripheral blood CD34 cell counts, and others have been evaluated in healthy donors with inconsistent results [2,6,7,[12][13][14]. When PBSC mobilizations in healthy donors started in our centre in 1997, only few clinical data were available.…”

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confidence: 99%

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Outcomes of 167 healthy sibling donors after peripheral blood stem cell mobilization with G-CSF 16μg/kg/day: efficacy and safety

Krejčí¹,

Janíková²,

Folber³

et al. 2015

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Mobilization of peripheral blood stem cells (PBSC) using the granulocyte colony-stimulating factor (G-CSF) has enabled the collection even from older donors and those with comorbidities. Several clinical parameters have been reported to predict the success of PBSC mobilization.The aim of our study was to evaluate the safety of PBSC donation in a cohort of 167 sibling donors after mobilization with G-CSF 16 μg/kg/day for 5 days during short-and long term follow-up and to analyse the efficacy, toxicity and factors influencing CD34+ mobilization capacity.All 167 sibling donors completed the established mobilization protocol. The median yield was 7.9x10 6 CD34 cells/kg per recipient weight. The optimal target dose of CD34 cells ≥ 4.0x10 6 /kg was achieved in 140 donors (84%). Only in 4 donors (2%) was the CD34+ yield < 2x10 6 /kg. No major toxicities occured. Factors associated with higher PBSC yields included age < 55 years (p= 0.001), male gender (p= 0.004), preapheresis CD34 cell counts > 51/μL (p < 0.001) and preapheresis leukocyte counts > 45.5 x 10 9 /L (p = 0.003). Comorbidity score, performance status and donor weight did not significantly influence PBSC yields. Long-term follow-up was possible in 60% (101/167) of the donors. The median length of follow-up from PBSC donation was 11.9 years. Most of these donors reported good or very good general health (91%), and no hematological malignancies were observed.The mobilization of PBSC in sibling donors with G-CSF 16 μg/kg/day is an effective and safe procedure with no significant short-and long-term toxicities.

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Section: Discussionmentioning

confidence: 99%

“…A G-CSF dose between 10 μg/kg to 16 μg/kg G-CSF is accepted as a standard and used by most centres worldwide [7,21].…”

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Outcomes of 167 healthy sibling donors after peripheral blood stem cell mobilization with G-CSF 16μg/kg/day: efficacy and safety

Krejčí¹,

Janíková²,

Folber³

et al. 2015

neo

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“…The gold standard for stimulating HSC to mobilise from BM into the PB is the administration of a recombinant human protein called granulocyte--colony stimulating factor (G--CSF) [10]. G--CSF fails to mobilise sufficient numbers of cells in 2--5% of healthy donors [11] and up to 15% to 60% of cancer patients [12,13].When G--CSF fails to mobilise adequate cell numbers, other mobilising agents may be administered [10]. HSC mobilisation and apheresis is typically performed over several days, …”

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confidence: 99%

Device and application development for haematopoietic stem and progenitor cell (HSPC) and mesenchymal stromal cell (MSC) 3D spheroid cultures

Futrega¹

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KeywordsAIM 2: Utilization of the high throughput microwell platform to manufacture HSPC/MSC spheroids to improve the efficacy of direct BM transplantation.AIM 3: Development of an improved microwell platform that retains spheroids within discrete microwells throughout culture. AIM 4:Characterization of HSPC surface marker change in response to microwell material. DEVICE AND APPLICATION DEVELOPMENT FOR HSPC AND MSC 3D SPHEROID CULTURES iiiChapter 2 describes the development of a high throughput HSPC/MSC 3D spheroid co--culture embodied in AIM 1. I developed a high throughput polydimethylsiloxane (PDMS) microwell platform that enabled the manufacture of thousands of uniform 3D multicellular co--culture spheroids. Spheroids were assembled such that each contained 25--to--400 BM--derived MSC and 10 CB--derived CD34 + cells (a cell population enriched for HSPC). The outcomes from this Chapter guided the design of the subsequent three chapters. The specific outcomes and subsequent study results were as follows:Chapter 3: As described in Chapter 2, only modest improvements in expansion could be achieved by co--culturing HSPC in 3D MSC spheroids using a microwell platform. We reasoned that the 3D spheroids could, however, function as a biologically active anchor to improve direct BM transplantation outcomes. In this Chapter, we contrasted transplantation methods, including the use of MSC suspensions and 3D multicellular spheroids to modulate human CB--derived CD34 + cell retention within the BM cavity of NOD/SCID gamma (NSG) mice. Analysis revealed that the BM of injected femurs in some animals was saturated with human cells, while distal haematopoietic tissue engraftment was poor. These data show, for the first time, that retention of human haematopoietic cells within the BM enhances local engraftment at the expense of systemic engraftment.Chapter 4: As identified in Chapter 2, improvements in 3D spheroid co--cultures will require that the microwell platform is compatible with repeated medium exchange or dilution feeding. Multiple partial or complete medium exchanges can displace spheroids from discrete microwells, and this can result in either the loss of spheroids from culture, or spheroid amalgamation when displaced microtissues fall into common microwells. In this Chapter, I describe the first microwell platform that incorporates a mesh to retain microtissues within discrete microwells. We called this platform the microwell--mesh. We show that bonding a nylon mesh with an appropriate pore size over the microwell openings allows single cells to pass through the mesh into the microwells during the seeding process, but subsequently retains assembled microtissues within discrete microwells.Chapter 5: As identified in Chapter 2, the presence of PDMS, the material used to fabricate the microwell platform, altered CD38 surface expression on CB--derived CD34 + cells. Previous reports have shown that inhibition of retinoic acid signaling down--regulated CD38 iv DEVICE AND APPLICATION DEVELOPMENT FOR HSPC AND MSC 3D SPHE...

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Granulocyte transfusions for treating infections in people with neutropenia or neutrophil dysfunction

Estcourt

Stanworth

Hopewell

et al. 2016

Cochrane Database of Systematic Reviews

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Background Despite modern antimicrobials and supportive therapy bacterial and fungal infections are still major complications in people with prolonged disease-related or treatment-related neutropenia. Transfusions of granulocytes have a long history of usage in clinical practice to support and treat severe infection in high-risk groups of patients with neutropenia or neutrophil dysfunction. However, there is considerable current variability in therapeutic granulocyte transfusion practice, and uncertainty about the beneficial effect of transfusions given as an adjunct to antibiotics on mortality. This is an update of a Cochrane review first published in 2005. Objectives To determine the effectiveness and safety of granulocyte transfusions compared to no granulocyte transfusions as adjuncts to antimicrobials for treating infections in people with neutropenia or disorders of neutrophil function aimed at reducing mortality and other adverse outcomes related to infection. Search methods We searched for randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2016, Issue 2). MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1937), the Transfusion Evidence Library (from 1980) and ongoing trial databases to 11 February 2016. Selection criteria RCTs comparing people with neutropenia or disorders of neutrophil dysfunction receiving granulocyte transfusions to treat infection with a control group receiving no granulocyte transfusions. Neonates are the subject of another Cochrane review and were excluded from this review. There was no restriction by outcomes examined, language or publication status. Data collection and analysis We used standard methodological procedures expected by the Cochrane Collaboration. Main results We identified 10 trials that met the inclusion criteria with a total of 587 participants. We also identified another ongoing trial. These trials were conducted between 1975 and 2015. None of the studies included people with neutrophil dysfunction. The studies differed in the type of infections they included. Six studies included both children and adults, however data were not reported separately for children and adults. The two newest studies gave granulocyte colony stimulating factor (G-CSF) to donors; both were stopped early due to lack of recruitment. Three studies re-randomised participants and therefore quantitative analysis was unable to be performed. Overall the quality of the evidence was very low to low across different outcomes according to GRADE methodology. This was due to many of the studies being at high risk of bias, and many of the outcomes being imprecise. There may be no difference in all-cause mortality over 30 days between participants receiving therapeutic granulocyte transfusions and those that did not (six studies; 321 participants; RR 0.75, 95% CI 0.54 to 1.04; very low-quality evidence). There were no differences between the granulocyte dose subgroups (< 1 x 1010 per day versus ≥ 1 x 1010 per day) (test ...

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G-CSF in Healthy Allogeneic Stem Cell Donors

Cited by 60 publications

References 64 publications

Outcomes of 167 healthy sibling donors after peripheral blood stem cell mobilization with G-CSF 16μg/kg/day: efficacy and safety

Outcomes of 167 healthy sibling donors after peripheral blood stem cell mobilization with G-CSF 16μg/kg/day: efficacy and safety

Device and application development for haematopoietic stem and progenitor cell (HSPC) and mesenchymal stromal cell (MSC) 3D spheroid cultures

Granulocyte transfusions for treating infections in people with neutropenia or neutrophil dysfunction

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