The inability to mobilize sufficient number of hematopoietic stem cells (HSC) using standard cytokine-assisted mobilization strategies excludes eligible patients from potentially curative autologous stem cell transplantation (ASCT). AMD3100, a novel antagonist of the SDF-1α / CXCR4 complex, has been reported to augment peripheral stem cell (PBSC) mobilization in patients undergoing their first planned stem cell collection attempt. AMD3100 can rapidly increase circulating CD34+ progenitor cells in preclinical murine models and healthy volunteers, alone or in combination with G-CSF. In phase II trials, when combined with G-CSF, AMD3100 appeared effective at mobilizing heavily pretreated patients during their first apheresis (Stiff, ASBMT, 2005). The ability of AMD3100 plus G-CSF to mobilize patients who were unable to collect significant CD34+ cells with G-CSF also has been observed. Patients undergoing their first attempt at PBSC mobilization were enrolled in a cross-over design trial comparing G-CSF with G-CSF and AMD3100 (Flomenberg, BLOOD, 2005). Nine patients did not mobilize PBSC when initially treated with G-CSF, but were subsequently collected when treated with AMD3100 plus G-CSF. In contrast, no patients on the AMD3100 + G-CSF arm failed to mobilize adequate PBSC.
AMD3100 has been available on compassionate use for patients, otherwise eligible for ASCT but who have failed to mobilize adequate PBSC. Effective rescue of patients was been achieved in >50% of the population (McGuirk, ASH, 2005). Our center has participated in this compassionate use program and seven patients (4 NHL, 1 Hodgkin’s Disease, 1 AILD, 1 myeloma) were enrolled in a local IRB- approved compassionate use protocol using AMD3100 in combination with G-CSF. A detailed analysis of these seven patients has been performed.
Pretreatment characteristics include: patient median age was 58, median # of previous chemotherapy regimens was 3, and that five patients had failed chemotherapy + growth factor based PBSC mobilization strategies. Two patients had undergone previous autologous transplantation and that of the 5 patients for whom PBSC collection was attempted, the median # of CD34 progenitors collected was 0.53 × 106/kg.
Results: 6 of seven patients had successful mobilization of CD34+ PBSC when treated with the combination treatment strategy with the median number of CD34+ progenitors/kg = 3.6 × 106 with a mean of 2.3 days for collection (median = 2 days). All six of the patients have since gone on to ASCT and all have had documented engraftment with median time to ANC of 500 by Day 12 and median time to platelet counts of 20,000 and 50,000 by Days 24 and 37, respectively. Only the myeloma patient who had previously undergone two independent ASCT, among other treatments, failed to mobilize PBSC and was unable to pursue ASCT. Thus, we confirm the ability to rescue G-CSF failures (1 patient) as well as demonstrate that patients who fail G-CSF plus chemotherapy mobilization attempts (5 of 6 patients) can effectively be rescued with a combination of AMD3100 and G-CSF. We have found this strategy safe and we recommend this combination mobilization strategy for patients with failed PBSC mobilization attempts to allow patients to pursue ASCT options.
