Stem Cell Mobilization in Normal Donors

Tabilio, Antonio; Falzetti, Franca; Giannoni, Claudia; Aversa, Franco; Martelli, Maria Paola; Rossetti, Massimo; Caputo, Pierfranco; Chionne, Fausto; Gambelunghe, Cristiana; Martelli, Massimo F.

doi:10.1089/scd.1.1997.6.227

Cited by 36 publications

(25 citation statements)

References 24 publications

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“…Hematopoietic Stem Cells Source-HSCs, obtained upon informed consent from donors for allogeneic HSC transplant, were mobilized in the peripheral blood by recombinant granulocyte colony-stimulating factor treatment and collected by superparamagnetic iron-dextran particles directly conjugated to anti-CD34 as previously described (12,15). The purity of the isolated cells was evaluated by flow cytometry using a phycoerythrin-conjugated monoclonal anti-CD34 antibody and challenged against a large panel of antigens characterizing late committed or mature hematopoietic cell types as previously reported (12).…”

Section: Methodsmentioning

confidence: 99%

“…The larger availability of oxygen, experienced by the mobilized HSC, enables it to be used as the driving substrate for the mitochondrial oxidative phosphorylation as well as for other extra-mitochondrial oxidative reactions. In this work we have studied the enzymatic features of the cellular oxygen consuming reactions in human HSCs recovered from peripheral blood, upon mobilization from bone marrow by the growth factor granulocyte colony-stimulating factor (11)(12)(13)(14), and isolated by immunoselection using as cell specific tag the CD34 antigenic marker.…”

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confidence: 99%

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Characterization of Mitochondrial and Extra-mitochondrial Oxygen Consuming Reactions in Human Hematopoietic Stem Cells

Piccoli

Ria

Scrima

et al. 2005

Journal of Biological Chemistry

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This study was aimed to characterize the mitochondrial and extra-mitochondrial oxygen consuming reactions in human CD34؉ hematopoietic stem cells. Cell samples were collected by apheresis following pre-conditioning by granulocyte colony-stimulating factor and isolated by anti-CD34 positive immunoselection. Polarographic analysis of the CN-sensitive endogenous cell respiration revealed a low mitochondrial oxygen consumption rate. Differential absorbance spectrometry on whole cell lysate and two-dimensional blue native-PAGE analysis of mitoplast proteins confirmed a low amount of mitochondrial respiratory chain complexes thus qualifying the hematopoietic stem cell as a poor oxidative phosphorylating cell type. Confocal microscopy imaging showed, however, that the intracellular content of mitochondria was not homogeneously distributed in the CD34؉ hematopoietic stem cell sample displaying a clear inverse correlation of their density with the expression of the CD34 commitment marker. About half of the endogenous oxygen consumption was extra-mitochondrial and completely inhibitable by enzymatic scavengers of reactive oxygen species and by diphenylene iodinium. By spectral analysis, flow cytometry, reverse transcriptase-PCR, immunocytochemistry, and immunoprecipitation it was shown that the extra-mitochondrial oxygen consumption was contributed by the NOX2 and NOX4 isoforms of the O 2 . producer plasma membrane NAD(P)H oxidase with low constitutive activity. A model is proposed suggesting for the NAD(P)H oxidase a role of O 2 sensor and/or ROS source serving as redox messengers in the activation of intracellular signaling pathways leading (or contributing) to mitochondriogenesis, cell survival, and differentiation in hematopoietic stem cells.

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

Characterization of Mitochondrial and Extra-mitochondrial Oxygen Consuming Reactions in Human Hematopoietic Stem Cells

Piccoli

Ria

Scrima

et al. 2005

Journal of Biological Chemistry

Self Cite

180

155

View full text Add to dashboard Cite

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“…As in other series, [14][15][16][17][18][19][20] most of the donors presented some immediate sideeffects, bone pain and headache being the toxicities most frequently observed, although they were easily managed with mild analgesics and resolved promptly after rhG-CSF discontinuation.…”

Section: Discussionmentioning

confidence: 52%

“…Finally, in 25 of them (5.3%) such information was not available. Median dose of rhG-CSF administered was 10 g/kg/day (range, [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20], with 387 (81.3%) donors receiving 10 g/kg/day. Seventy-two donors received Ͼ10 g/kg/day (median 12 g/kg; range, 10.8-20), and only 17 donors (3.6%) received Ͻ10 g/kg/day (median 5 g/kg; range, 4-9).…”

Section: Rhg-csf Administrationmentioning

confidence: 99%

Administration of recombinant human granulocyte colony-stimulating factor to normal donors: results of the Spanish National Donor Registry

Rubia

Martı́nez²,

Solano³

et al. 1999

Bone Marrow Transplant

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Summary:A Spanish National PBPC Donor Registry has recently been established for short-and long-term safety data collection in normal donors receiving rhG-CSF. To date, 466 donors have been included in the Registry. Median (range) dose and duration of rhG-CSF administration was 10 g/kg/day (4-20) and 5 days (4-8), respectively. Donors underwent a median of two aphereses (range, 1-5). Adverse effects consisted mainly of bone pain (90.2%), headache (16.9%) and fever (6.1%), but no donor discontinued rhG-CSF prematurely due to toxicity. Side-effects were more frequent in donors receiving Ͼ10 g/kg/day than in those with lower doses (82.8% vs 61.8%; P = 0.004). A significant decrease between baseline and post-apheresis platelet counts was the most important analytical finding (229 ؋ 10 9 /l vs 140 ؋ 10 9 /l; P Ͻ 0.0001), with a progressive reduction in platelet count with each apheresis procedure. One donor developed pneumothorax that required hospitalization due to central venous line placement. The mean CD34 ؉ cell dose collected was 6.9 ؋ 10 6 /kg (range, 1.3-36), with only 14 donors (2.9%) not achieving a minimum target of CD34 ؉ cells of 2 ؋ 10 6 /kg. No definitive information about potential long-term side effects is yet available. However, we hope this National Registry will serve as a useful basis for better monitoring of the efficiency and side-effects of cytokine administration in healthy people. Keywords: granulocyte colony-stimulating factor; normal donors; stem cell mobilization; side-effects Recombinant human granulocyte colony-stimulating factor (rhG-CSF) is being widely used to treat neutropenia secondary to chemotherapy and to collect peripheral blood progenitor cells (PBPC) for use in autologous transplantation. [1][2][3] More recently, rhG-CSF has been given to healthy people for granulocyte collection, 4,5 and to mobilize and collect PBPC for allogeneic transplants. [6][7][8][9][10] In the allogeneic setting, the routine use of mobilized PBPC must be based not only on clinical results, but also on the safety of donors. remain important issues. Regarding this, the optimal dose and schedule of rhG-CSF for mobilization of PBPC have not been definitively established, and specific information about short-and long-term biological and clinical effects of rhG-CSF in normal donors is still limited. Thus, a prolonged follow-up of donors is clearly needed in order to rule out the development of toxicity and to ensure that administration of this cytokine to healthy individuals is completely devoid of long-term side-effects. This task will be more easily approached by the development of PBPC national or international donor registries that allow the inclusion of higher number of donors. 11,12 In Spain, a National PBPC Donor Registry has recently been developed to address potential adverse effects of the administration of rhG-CSF to normal donors for PBPC mobilization and collection. The objectives of this registry include a standardized data collection for the different centers administering rhG-CSF to normal d...

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“…2 Although improvements to date have increased our ability to predict early hematopoietic engraftment, to our knowledge no one has evaluated the influence of body weight on PBSC enumeration and engraftment. It was suggested by some studies 25,26 but not others 13,27,28 that obese individuals have greater PBSC yields. The explanation for such variability remains poorly understood and it could be related to different rates of metabolism of growth factors or an artifact of the cell dose calculation in obese patients.…”

mentioning

confidence: 92%

Comparison of autologous peripheral blood stem cell dosing by ideal vs actual body weight

Waples

Moreb

Sugrue

et al. 1999

Bone Marrow Transplant

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Summary:In this retrospective study, we evaluated the predictability of PBSC dose for hematopoietic engraftment comparing that calculated by ideal body weight (IBW) vs another calculated by actual body weight (ABW) for each patient. Sixty-three consecutive patients treated similarly using one transplant protocol were analyzed. While all patients had data available on CFU-GM and nucleated cells (NC), data on CD34 + enumeration was present only in 34 patients. We found that 49% of the patients were greater than 25% over their IBW. In addition, least-squares linear regression was used to assess the strength of the linear relationship between the inverse of cell dose/kg of ABW or IBW and time to AGC or platelet engraftment and showed no difference in r 2 values for platelet engraftment, while using dose/kg of IBW greatly improved the ability of NC (r 2 improved from 0.19 for ABW to 0.35 for IBW) and CFU-GM (r 2 improved from 0.35 for ABW to 0.53 for IBW) to predict time to AGC engraftment, but did not change the CD34 r 2 . Hazard ratios were estimated using Cox proportional hazards regression and in all instances were found greater than 1.0 indicating that the probability of engraftment increased as cell dose/kg ABW or IBW increased. Finally, our data showed that 10 patients (16%) could have had one less apheresis procedure performed to obtain their set target stem cell dose calculated per kg IBW rather than ABW. In conclusion, PBSC dose per kg IBW is as good or better predictor of engraftment of AGC and may lead to cost savings in a certain subset of patients. Keywords: autologous stem cell transplantation; cell dose; actual body weight; ideal body weight High-dose chemotherapy (HDC) with peripheral blood stem cell (PBSC) rescue is an acceptable form of therapy for high-risk and metastatic breast cancer, relapsed and refractory Hodgkin's or non-Hodgkin's lymphoma, multiple myeloma, and other malignancies. Utilization of HDC with PBSC support has largely replaced bone marrow as the source of autologous hematopoietic stem cells. 1-6 PBSC Correspondence: Dr J Moreb, Division of Hematology/Oncology, PO Box 100277, Gainesville, FL 32610-0277, USA Received 31 July 1998; accepted 2 December 1998 products minimize the chief side-effects of HDC by fast reconstitution of hematopoiesis. In early studies, the PBSC product was evaluated prospectively by total number of nucleated or mononuclear cells and retrospectively by CFU-GM per kilogram of actual body weight, the value of which is known to correlate with days to engraftment of platelets (PLT) and absolute granulocyte counts (AGC). [7][8][9][10][11][12][13][14][15][16] Presently, the stem cell product is characterized in most laboratories by the number of CD34 + , CFU-GM, and total mononuclear cells per kilogram patient actual body weight (ABW). 1,[17][18][19][20] The number of CD34 + cells correlates well with CFU-GM content and serves as a better predictor of engraftment than total mononuclear cells per kilogram of ABW. 21,22 Recent evidence suggests that markers of primi...

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Stem Cell Mobilization in Normal Donors

Cited by 36 publications

References 24 publications

Characterization of Mitochondrial and Extra-mitochondrial Oxygen Consuming Reactions in Human Hematopoietic Stem Cells

Characterization of Mitochondrial and Extra-mitochondrial Oxygen Consuming Reactions in Human Hematopoietic Stem Cells

Administration of recombinant human granulocyte colony-stimulating factor to normal donors: results of the Spanish National Donor Registry

Comparison of autologous peripheral blood stem cell dosing by ideal vs actual body weight

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