autologous peripheral blood hematopoietic cell transplantation ( auto - pbhct ) is a well - established therapeutic option for patients with a variety of hematologic malignancies .
mobilization of peripheral blood progenitor cells ( pbpc ) for auto - pbhct can be accomplished by using cytokines , most commonly granulocyte - colony stimulating factor ( g - csf ) , either alone or in combination with chemotherapy ( e.g. , cyclophosphamide , etoposide , cytarabine , etc . ) or plerixafor [ 1 , 2 ] .
recently reported phase iii studies have also shown superiority of the combination of g - csf with plerixafor over g - csf alone for mobilizing pbpc in patients with non - hodgkin lymphoma ( nhl ) and multiple myeloma ( mm ) [ 3 , 4 ] .
plerixafor acts by selective and reversible antagonism of cxcr4 on cd34 + hematopoietic stem cells ( hsc ) .
this results in disruption of its interaction with cxcl12 ( formally sdf1 ) on bone marrow stromal cells , that cause a rapid release of stem and progenitor cells from bone marrow into peripheral blood .
while plerixafor - based pbpc mobilization can circumvent the need for chemotherapy to mobilize cd34 + pbpcs , to our knowledge no prospective trials comparing plerixafor plus g - csf to chemomobilization have been published to date .
limited data on murine models suggest that a combination of plerixafor and chemotherapy may be more effective than the use of plerixafor alone for pbpc mobilization . despite the promising results of plerixafor and g - csf for pbpc mobilization in patients with mm and nhl [ 3 , 4 , 68 ] , the use of chemotherapy and g - csf - based regimens to mobilize pbpc remains standard practice in many transplant centers .
this decision is often influenced by a desire to improve collection yield , reduce mobilization failures especially in patients who are elderly , heavily pre - treated , and have poor bone marrow cellularity , and/or as an attempt to provide disease control [ 911 ] .
limited data are available on the preemptive use of plerixafor salvage in patients failing to collect adequate numbers of pbpc with chemotherapy and g - csf - based mobilization [ 1214 ] , and this topic has been reviewed recently .
herein we report our experience from two north american transplant centers in a series of patients who received plerixafor salvage while failing chemotherapy and g - csf mobilization .
for patients undergoing chemotherapy and g - csf - based mobilization , it is standard operating procedure at both transplant centers to measure peripheral blood cd34 + cell count daily when the patient 's white blood cell ( wbc ) count recovers to 4,000/l or from day + 12 ( after chemotherapy ) onwards ( whichever occurs first ) .
patients destined to fail pbpc chemomobilization were defined as ( i ) those with a peak peripheral blood cd34 + cell count of < 10/l following wbc count recovery ( wbc count of 4,000/l ) after chemotherapy - induced nadir or ( ii ) those who failed to collect at least 1  10 cd34 + cells / kg after two apheresis sessions . in these patients failing chemomobilization , we administrated plerixafor at a dose of 0.24  mg / kg subcutaneously 10 hours prior to apheresis in conjunction with g - csf ( 10  g / kg ) , as a preemptive salvage strategy . all collections were performed with a cobe spectra apheresis system ( caridianbct , lakewood , co ) , by processing three to four blood volumes .
it is the institutional policy at both transplant centers to routinely target collection of 5  10 cd34 + cells / kg .
determination of peripheral blood cd34 + cell count and cd34 + cell content of the apheresis product was performed at the georgia health sciences university hla laboratory and west virginia university hospitals flow cytometry laboratory .
the bd facscanto ii flow cytometer , ( becton dickinson , san jose , ca ) was used for all analyses .
after red blood cell lysis , washed samples were used for cd34 + enumeration with pe - labeled , 8g12 clone , immunoglobulin g1 ( becton dickinson , san jose , ca ) based on international society of hematotherapy and graft engineering ( ishage ) guidelines .
the final products were cryopreserved in 10% dmso using a controlled rate freezer and stored in liquid nitrogen .
successful mobilization was defined as a total of 2  10 cd34 + cells / kg patients body weight in the final product .
data was collected on mobilization and transplant outcomes through an electronic data base , prospectively maintained at each participating institution and analyzed utilizing spss version 13.0 .
patient characteristics and transplantation outcomes of 16 patients who were failing chemomobilization ( as defined above ) and received preemptive plerixafor are summarized in table 1 .
patients had received a median of two lines of therapies ( range 13 ) prior to pbpc mobilization . after recovering from chemotherapy - induced count nadir ( i.e. , wbc  4000/l ) , 15 patients had a peak peripheral blood cd34 + cell count of < 10  l .
five patients underwent at least 2 sessions of apheresis but were unable to collect 1 million cd34 + cells / kg .
these patients subsequently received a median of two doses of plerixafor salvage ( range 18 ) .
the median number of apheresis sessions was 3.5 ( range 27 ) , and the median number of cd34 + cells collected was 3.9  10 cells / kg ( range 2.47.8 ) . utilizing a cutoff of 2  10 cd34 + cells / kg , all patients who received plerixafor had a successful collection .
nineteen percent of the patients were able to collect 5  10 cd34 + cells / kg .
three patients ( one with hodgkin lymphoma and two with nhl ) required more than four doses of plerixafor , but all eventually collected 2  10 cd34 + cells / kg .
the median peak peripheral blood cd34 + cell count prior to plerixafor administration was 3.5/l ( range 015 ) and increased to 6/l ( range 247 ) after the first dose of plerixafor ( p = 0.03 ) .
93% of the patients had a peak peripheral blood cd34 + cell count of < 10/l before plerixafor salvage .
four patients had a peak peripheral blood cd34 + cell count of 1/l before plerixafor salvage .
kinetics of peripheral blood cd34 + cell and wbc count changes after each dose of plerixafor for these 4 patients is shown in table 2 .
after transplantation , the median time to neutrophil and platelet engraftment was 10 days ( range 915 ) and 20 days ( range 929 ) , respectively . in order to identify predictors of response to plerixafor salvage ,
as expected , patients with a higher peripheral blood cd34 + cell count at the time of the first plerixafor dose had a higher magnitude of change in their peripheral blood cd34 + cell counts ( r = 0.58 , p = 0.01 ) .
only three patients had a cd34 + cell count of 10/l before the first dose of plerixafor , and their median increase was 18/l compared to 6/l for patients who had peripheral blood cd34 + cell counts of < 10/l however , this difference was not statistically significant ( p = 0.3 ) .
we did observe a positive correlation between peak peripheral blood cd34 + cell count before the first dose of plerixafor and the total number of cd34 + cells collected at apheresis ( r = 0.62 ; p = 0.01 ) .
of the 41 collections with plerixafor , the mean cd34 + cell dose collected was 0.79  10 cd34 + cells / kg from 25 collections in patients with a peripheral blood cd34 + cell count < 10/l versus 2.09  10 cd34 + cells / kg from 16 collections in patients with a cd34 + cell count greater than 10/l ( p = 0.001 ) .
correlation analyses were performed in order to define an optimal cutoff of wbc count that can be used as a marker for the initiation of plerixafor salvage , which showed that wbc count had no correlation with a change in cd34 + cell count after the first dose of plerixafor ( r = 0.21 , p = 0.41 ) .
utilizing the median wbc count of 32/l at the time of administration of plerixafor in our patients , we found that we were able to collect a higher number of cd34 + cells in patients who had a wbc count 32/l as compared to those with a wbc count > 32/l ( 1.67  10/kg versus 0.8  10/kg , p = 0.02 resp . ) .
our limited multicenter outcomes data suggest that the addition of plerixafor as a preemptive salvage may rescue patients who are destined to fail chemotherapy and g - csf - based pbpc mobilization .
in our series we used plerixafor salvage to rescue an otherwise failed attempt for chemomobilization , which contrasts with prior studies where plerixafor was used to remobilize patients who had failed prior mobilization attempts .
this is also in contrast to studies where plerixafor was routinely given to patients undergoing chemomobilization . in our series plerixafor
was given after recovery from chemotherapy - induced count nadir ( median of 11.5 days after chemotherapy ) and resulted in successful cd34 + cell collection in all patients , who were otherwise likely to fail chemomobilization .
interestingly patients with a wbc count of  32/l were able to collect a higher number of cd34 + cells .
this is in contrast to earlier data [ 1215 ] that indicated limited efficacy of plerixafor in patients with a lower wbc count .
this discrepancy can be a reflection of the decreased efficiency of the collection process in patients with a higher wbc count or possibly a reflection of timing of plerixafor administration .
generally a cd34 + cell count of 1013/l is used as a cutoff for initiating apheresis following cytokine only , cytokine plus plerixafor , or chemomobilization in majority of transplant centers in the country . the median cd34 + cell count of our patients was only 3.5/l with 82% less than 10/l at the time of the first plerixafor dose , and all patients were able to collect a minimum of 2  10 cells / kg . however
, a valid cutoff for peripheral blood cd34 + cell count to initiate apheresis when plerixafor is used as a salvage for failed chemomobilization is unknown .
patient characteristics and institutional preference will likely continue to influence the choice for mobilization strategy in patients undergoing an auto - pbhct . while no prospective data are available to demonstrate better efficacy or cost effectiveness of plerixafor - based mobilization over chemotherapy - based mobilization , our preliminary data provide safety and efficacy data for plerixafor salvage to rescue patients failing chemotherapy - based pbpc mobilization .
 the combination of filgrastim ( g - csf ) and plerixafor is currently approved for mobilizing peripheral blood progenitor cells in patients with non - hodgkin lymphoma and multiple myeloma undergoing autologous peripheral blood hematopoietic cell transplantation . 
 however , chemotherapy and g - csf - based mobilization remains a widely used strategy for peripheral blood progenitor cell collection . in this paper 
 we describe our experience from two north american transplant centers in a series of patients who received salvage plerixafor while failing chemotherapy and g - csf mobilization . 
 patients received a median of two doses of plerixafor salvage upon failure to mobilize adequate number of peripheral blood progenitor cells at neutrophil recovery . 
 the use of plerixafor was associated with a 2.4-fold increase in peripheral blood cd34 + cell count and 3.9-fold increase in total cd34 + cell yield . 
 all patients were able to collect 2  106 cd34 +  cells / kg with this approach . 
 these results were more pronounced in patients with a higher cd34 + cell count at the time of the first plerixafor dose . 
 interestingly , peripheral blood white blood cell count was not shown to correlate with a response to plerixafor . 
 our results provide safety and efficacy data for the use of plerixafor in patients who are destined to fail chemomobilization . 