Factors affecting mobilization of CD34+ cells in normal donors treated with filgrastim

Summary:We report the case of a healthy donor who was mobilized for the purpose of performing an unrelated donor transplantation with subcutaneous injections of rhG-CSF. Because of accidental loss of progenitors, 3 days after completing the first collection, the donor was mobilized again with rhG-CSF, and progenitors were collected. While a similar increase in the pre-apheresis leukocyte count was observed in both procedures, fewer mononuclear cells were mobilized during the second rhG-CSF course, resulting in a poor CD34 + yield. These data suggest that an 8-day interval between commencement of rhG-CSF mobilizations is insufficient to predict an efficient collection of hematopoietic progenitors to ensure engraftment after bone marrow transplantation. Bone Marrow Transplantation (2000) 26, 351-352. Keywords: mobilization; granulocyte colony-stimulating factor; CD34 ϩ peripheral blood progenitor cells Transplantation of recombinant human granulocyte colonystimulating factor (rhG-CSF)-mobilized peripheral blood progenitor cells (PBPCs) is now being increasingly used for the treatment of hematological malignancies and solid tumors. A 4-5 day course of 5-10 g/kg/day rhG-CSF generally allows collection of sufficient PBPCs for transplantation (Ͼ2.0 ϫ 10 6 CD34 ϩ cells/kg) by one leukapheresis in the majority of donors. This avoids the need for general anaesthesia and marrow harvest. To date, available literature on short-term second PBPC mobilization in healthy donors is limited 1-3 and, although a reduction in PBPC yield is inversely associated with time intervals between aphereses (shortest interval described between procedures of 16 days), 3 in all cases the reduction was not severe enough to prevent effective PBPC harvesting during the second mobilization. Thus, it is unclear what is the minimum period of time required to predict an adequate number of PBPCs being mobilized and subsequently collected after repeated rhG-CSF mobilization schedules.

Section: Discussioncontrasting

confidence: 96%

Re-mobilization of peripheral blood progenitor cells within a short time interval fails to achieve effective progenitor cell yields

Vallejo¹,

Lozano²,

Ortuño³

et al. 2000

“…Our data, as well as that reported by others, 15,34,35 clearly indicate that some volunteers are intrinsically poor responders to rhG-CSF, although due to low numbers, no specific characteristics could be identified as a predictive factor for response to rhG-CSF administration in these 'poor' mobilizers. In these cases, alternative approaches to PBPC mobilization need to be investigated.…”

Section: Discussionsupporting

confidence: 82%

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

Rubia

Martı́nez²,

Solano³

et al. 1999

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...

“…11 It has been demonstrated that, at least for rhG-CSF at doses between 5 and 10 g/kg/day, a dose-response relationship does exist with regard to the yield of CD34 ϩ cells. 12 Although rhG-CSF doses up to 24 g/kg/day have been reported, 13 experience with such high amounts remains limited. The purpose of this dose escalating study was to determine whether escalating split doses of lenograstim ranging from 8 to 15 g/kg do result in an increase in the number of CD34 ϩ cells harvested and whether higher doses of G-CSF might allow collection earlier.…”

mentioning

confidence: 99%

Lenograstim-mobilized peripheral blood progenitor cells in volunteer donors: an open label randomized split dose escalating study

Basara

Schmetzer

Blau

et al. 2000

Summary:Mobilization of peripheral blood cell progenitor cells was investigated in 36 healthy sibling donors using three different split doses of glycosylated rhG-CSF (lenograstim). The donors were randomized into three groups: group 1 was given lenograstim at 8, group 2 at 11 and group 3 at 15 g/kg/day in two split doses, subcutaneously for 4 and 5 days, respectively. Leukapheresis was performed on day 4 or 5 depending on the WBC and CD34 ؉ cell count. We were able to demonstrate that there was a significant correlation between circulating CD34 ؉ cells on the day of harvest and CD34 ؉ cells in the apheresis products in all three groups. The number of CD34 ؉ cells pre-apheresis was inversely correlated with age in group 1 and group 2. However, in group 3, the number of CD34 ؉ cells preapheresis did not correlate with age. There was also a difference between the number of progenitor cells mobilized in the three dose groups regarding the time of harvest. Apheresis was performed in groups 1 and 2 on day 5 of mobilization in order to obtain a sufficient number of stem cells for allogeneic transplantation. In contrast, with the split dose of 15 g/kg/day, harvest could be routinely performed on day 4 of stimulation. We conclude that lenograstim given twice a day at doses of 8, 11 and 15 g/kg/day provided different CD34 ؉ cell yields in normal donors, in particular, with regard to the time of harvest. The number of CD34 ؉ cells preapheresis was not correlated with age in the group of donors mobilized with a split dose of 15 g/kg/day, indicating that this dosage might also be suitable for older donors. Bone Marrow Transplantation (2000) 25, 371-376.