Successful PBSC Mobilization with High-Dose G-CSF for Patients Failing a First Round of Mobilization

Abstract

PBSC are the preferred source of stem cells for autologous transplantation. However, regardless of the mobilization procedure used, 10%-20% of patients fail to collect an adequate number to ensure prompt engraftment. There is as yet no standard mobilization procedure for patients who fail a first mobilization attempt. Here, we describe a highly efficient strategy to obtain an adequate number of stem cells for patients who failed a first mobilization attempt. Seventy-four patients with various hematologic malignancies underwent initial mobilization with various regimens including hematopoietic growth factors with or without chemotherapy. In 72% of patients, > or =2 x 10(6) CD34+ stem cells/kg were collected in the initial mobilization attempt, and patients engrafted in a median of 10 days for neutrophils and 12 days for platelets. Eighteen patients failed to mobilize adequate numbers of stem cells, defined as the inability to collect 0.2 x 10(6) CD34+ stem cells/kg/day in the first 2-3 days. These patients had their apheresis halted. Patients were immediately given G-CSF (32 microg/kg/day) for 4 days as a second attempt at mobilization. Eighty-eight percent of these patients achieved the target of > or =2 x 10(6) CD34+ cells/kg, with a median duration of apheresis of 5 days (including the first and second mobilizations). The mean CD34+ cells/kg/day increased after administration of high-dose G-CSF from 0.16 after the first mobilization attempt to 0.61 (p = 0.0002) after the second mobilization. All patients engrafted in a median of 11 and 13 days for neutrophils and platelets, respectively. We conclude that patients whose apheresis yield is <0.4 x 10(6) CD34+ cells/kg after the first two apheresis collections can be successfully mobilized if high-dose G-CSF is administered immediately and continued until achieving > or =2 x 10(6) CD34+ stem cells/kg.

Improving stem cell mobilization strategies: future directions

“…Positive results historically reported for high-dose G-CSF remobilization regimens 83,90 have not been notably strengthened or refuted by recent research. 23,93 Gazitt et al 83 reported that the administration of G-CSF 32 mg/kg s.c. daily for 4 days before apheresis and continuing until the last day of apheresis resulted in successful remobilization in 88% of 18 patients whose first mobilization attempt was unsuccessful; most of these patients had NHL.…”

“…72,82 When G-CSF alone is used for stem cell mobilization, it is administered at doses ranging from 10 mg/kg s.c. daily to 32 mg/kg s.c. daily, beginning at least 4 days before the first apheresis session and continued until the last apheresis session. 65,83 After transplantation, the median time to granulocyte engraftment has been reported to be 11 days, and plt engraftment has been reported to be B11-14 days. 27,28 Mobilization with G-CSF is generally well tolerated; common AEs are bone pain, headache, anemia and decreased plt counts.…”

“…After an initial mobilization attempt, if too few CD34 þ cells are collected to ensure prompt engraftment, patients often undergo additional mobilization attempts, which increase the risks associated with treatment. 83 Several salvage regimens have been developed to improve mobilization in patients in whom a first mobilization attempt with G-CSF alone fails to result in collection of an adequate cell dose. These salvage regimens include high-dose G-CSF and combinations of G-CSF with other cytokines, such as GM-CSF.…”

“…23,93 Although there is no standard protocol for high-dose G-CSF administration, doses ranging from 16 to 32 mg/kg s.c. daily to 12-16 mg/kg s.c. twice daily have been considered high-dose regimens even though some of the available data apply to patients with aplastic anemia, solid tumors or hematological malignancies other than NHL. 23,83,91 Early published studies of G-CSF for primary mobilization presented opposing viewpoints. 91,92 Zeller et al 91 reported that compared to a lower dose regimen (G-CSF 10 mg/kg s.c. daily beginning 4 days before apheresis, n ¼ 33), highdose G-CSF (12 mg/kg s.c. twice daily beginning 4 days before apheresis, n ¼ 34) resulted in higher CD34 þ cell yields per apheresis session (4.82 Â 10 8 /kg vs 1.13 Â 10 8 /kg and 4.04 Â 10 8 /kg vs 0.93 Â 10 8 /kg) and fewer mean apheresis sessions (2 vs 3) in patients with NHL, HD or cancer of the testis.…”

True

“…Peripheral blood mononuclear cell apheresis collected from a MM patient mobilized with 6 g/m 2 of cytoxan plus 250 g/m 2 of GM-CSF 39 were stained for stem cell markers (CD34-PE and CD45-FITC) and sorted for CD34 + /CD45 dim stem cells as described in the Methodology section. This particular patient had a total of 8.6% stem cells.…”