Plerixafor (Mozobil®, Genzyme, Cambridge, MA) is approved for hematopoietic progenitor cell (HPC) mobilization into peripheral blood (PB) in combination with granulocyte colony stimulating factor (G-CSF) at ∼11 hours (hr) prior to apheresis initiation. Since apheresis facilities typically open at 8-9 AM, this 11 hr interval requires plerixafor dosing between 9-10 pm, impractical unless the patient self-administers the drug.
No studies have examined mobilization kinetics beyond 15 hr in the target MM and NHL patient population. This is the first study in this target population to examine a total interval time of 17-18 hr post-plerixafor, important because, practically, leukapheresis may not be initiated until 10-11 AM. Even if initiated earlier between 8-9 AM, a standard leukapheresis typically lasts ∼3 hr. Therefore, it is important to rule out a significant decrease in PB [CD34+] extending through this interval.
A single-center, prospective cohort, IRB-approved study where 11 patients with NHL and MM underwent HPC mobilization from March 2010 to October 2011. Patients met the same entry criteria specified in the initial studies leading to FDA approval. Plerixafor 240 ug/kg was administered at 5pm on day 4 of AM G-CSF 10 ug/kg. PB [CD34+] and [CD34+CD38-] concentrations were enumerated every 2 hours from 5PM to 7AM and immediately pre-apheresis on day 5, for a total interval time of 17-18 hr post-plerixafor. Leukapheresis (3 total blood volumes) was performed if the 7 am peripheral blood CD34+ concentration was ≥10/uL. Data was analyzed used mixed model analysis of repeated measures.
9 of 11 subjects , including all 5 patients who had received 3-9 cycles of lenalidomide, achieved a CD34+ product count of >5x106/kg with a single leukapheresis. All 9 patients (in contrast to the other 2) had a pre-plerixafor PB CD34+ concentration > 10/uL. PB [CD34+] did not differ between 10-18 hours post-plerixafor (p≈0.8). In contrast, PB [CD34+CD38-] increased from 10 to 18 hours post-plerixafor (p=0.03). 10 subjects underwent transplant with a median CD34+ dose of 6.0x106/kg (range 3.8-10.8x 106/kg) and engrafted within normal time frames. Using post- to (5PM) pre-plerixafor [CD34+] ratios to compare efficacy of plerixafor kinetics, the median ratio of the 17-18hr post/pre-plerixafor [CD34+] was 4.0 (range 1.8-6.8), not significantly different (p=0.09) from that of the peak post/pre-plerixafor [CD34+] of 4.7 (range 1.9-9). The 3 subjects with lowest mobilization had diabetes, but the peak post/pre [CD34+] ratio was not adversely affected. Two of these three reached their peak [CD34+] mobilization at 8hr post-plerixafor, whereas all other donors reached their peak [CD34+] ≥ 10hr post-plerixafor. The correlation coefficient of 0.54 between the PB [CD34+] and [CD34+CD38-] was weak.
In MM and NHL patients with adequate pre-plerixafor CD34+ concentration, which includes those with prior lenalidomide, leukapheresis initiated 17-18 hours post-plerixafor may not impair CD34+ product yield and may increase more primitive CD34+CD38- yield. Patient with risk factors for poor mobilization, such as diabetes or salvage chemotherapy, may be an exception. The three donors with post-plerixafor PB [CD34+] < 100/uL all had diabetes, which has been established to impair G-CSF induced stem cell mobilization. Our data supports murine data that plerixafor overcomes sympathetic nervous system-related defects in mobilization, since the peak post/pre plerixafor [CD34+] ratio was > 4 in all 3 patients. Interestingly, the donor with the second highest mobilization also had diabetes but a low peak/pre [CD34+] ratio of 2.9 (i.e. excellent mobilization with G-CSF alone); her mobilization impairment from diabetes may have been overcome by concurrent use (for asthma) of the β2-adrenergic agonist albuterol, previously associated with high mobilization. Consistent with previous studies, the 2 patients with poor [CD34+] mobilization reached their peak PB [CD34+] < 11 hours post-plerixafor. Finally, given the weak correlation between PB [CD34+] and [CD34+CD38-] , the utility of using PB [CD34+CD38-] to help determine the optimal time for collection may be worth exploring, given the correlation between CD34+CD38- graft content and long-term hematopoietic reconstitution in autologous transplantation.
Off Label Use: Plerixafor administered up to 18 hours prior to apheresis initiation, rather than the FDA-approved 11 hours.
Author notes
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