Phase II Study of Stimulation of Healthy Sibling Donors with Single-Shot Pegfilgrastim - Update (EUDRACT Nr: 2005-004971-39)

Introduction: For allogeneic stem cell donation it is current practice to mobilize with G-CSF bid for 5 days. Here, the feasibility of mobilizing with a single injection of pegfiligrastim was examined in a phase II study with an emphasis on donor safety and product composition.

Results: 28 sibling donors (14 female, 14 male) of median age 50 (range 22 - 69) years were included in the study. The median donor weight was 80 (range 45 - 119) kg and that of recipients was 75 (range 47 - 127) kg. Large volume apheresis (4 x total blood volume) was possible in 26 donors 4 days after the administration of pegfilgrastim 12 mg s.c. The aphereses were performed when CD34⁺cells exceeded 10/µl peripheral blood, median CD34⁺concentration prior to apheresis being 66.25 (range 22.8 - 136.6) cells/µl. White blood cell (WBC) concentration peaked on day 4 of stimulation with a median 52.55 (range 22.8 - 85) GPT/l. The lactate dehydrogenase (LDH) and C-reactive protein (CRP) levels increased to a median 2.55 (range 1.36 - 6.02) and 3.23 (range 0.47 - 15.13) x upper limit of normal (ULN) respectively. There were no changes in creatinine, electrolytes or transaminases. Two donors required filgrastim in addition to the pegylated G-CSF, with the aphereses being performed on day 5 after pegfilgrastim. Six donors required more than one apheresis.

In 25/28 donors, a median of 6.5 (range 4.6 - 14.5) x10⁶CD34⁺/kg recipient body weight were collected. In three donors the yield was below 4x10⁶CD34⁺/kg recipient body weight, i.e. 3, 3.4 and 3.6 respectively. The yield of CD34⁺/CD133⁺cells was median 4.45 (range 2.74 - 12.5) x10⁶/kg recipient body weight.

In 27/28 cell concentrates, the number of CFU-GM amounted to median 126 (range 65 - 323) /10⁵mononuclear cells. The yield of CD3⁺cells was median 3.25 (range 1.4 - 6.2) x10⁸/kg recipient body weight. The CD3⁺/CD8⁺and CD3⁺/CD4⁺ratios were 0.92 (range 0.33 - 2.58) and 2.14 (range 0.85 - 4.16) x10⁸/kg, respectively. The yield of natural killer (NK) cells was median 0.4 (range 0.2 - 1) x10⁸/kg recipient body weight.

On the first collection day, 27/28 donors reported through a standardized questionnaire that the stimulation was well tolerated, although 26 experienced bone pain, which was strong in 11 cases. Other side effects such as cephalea, tiredness or inability to work were reported only in single cases.

Hematopoietic Stem Cell Transplants were performed without complications. WBC recovery occurred on median day 14 (range 8 - 34) after HSCT. Acute GvHD > Gr. 3 was noted in one patient only. No rejection was observed.

Conclusion: Pegfilgrastim is a feasible alternative to conventional bid filgrastim for stem cell mobilization. A single application was able to mobilize sufficient CD34⁺/CD133⁺cells into the peripheral blood for successful collections. The most frequent adverse effects were elevation of CRP and/or LDH and bone pain.