Plerixafor Group Research Articles

Inclusion of Plerixafor Increases the Efficacy of Stem Cell Harvesting in Poorly Mobilizing Patients with Multiple Myeloma and Lymphoma

Introduction: Up to 30% of patients (pts) undergoing stem cell mobilization with granulocyte colony-stimulating factor (G-CSF) with or without prior chemotherapy mobilize poorly. Plerixafor is a potent CXCR4 receptor antagonist that is licensed for stem cell mobilization in autologous stem cell donors with multiple myeloma (MM) or lymphoma, who show poor mobilization after stimulation with recombinant G-CSF (r-metHuG-CSF, Filgastrim). Here we present our experience with plerixafor in poorly mobilizing autologous donors.Patients and Methods: We performed 35 stem cell collections between January 2011 and December 2014 in 28 poorly mobilizing autologous donors with MM (n=14), non-Hodgkin lymphoma (NHL, n=11), Hodgkin lymphoma (n=1) or both MM & NHL (n=2), adding plerixafor to the stimulation regimen with recombinant G-CSF. Known risk factors for poor mobilization included: diagnosis of lymphoma (50%); older age (61% >60y at apheresis); >1 chemotherapy lines (86%) & pretreatment with melphalan (18%). Median age of patients (pts) was 61 years (y, range 37-72y) at stem cell collection and 15 of the 28 pts were females. All pts received previous treatment with G-CSF (2x5µg/kg body weight [BW]) followed by a large volume leukapheresis (maximal 4 x total blood volume). All pts received 0.24 mg/kg BW plerixafor following insufficient mobilization of CD34+ cells into the peripheral blood (PB, <10/µl CD34+ cells) - either after peripheral reconstitution of white blood cells (WBC, >1 Gpt/l) following chemotherapy (n=22, 79%) or after 5 days of stimulation with G-CSF in steady state (n=6, 21%). Six pts treated with chemotherapy prior to mobilization received a second dose of plerixafor in response to insufficient CD34+ cell harvesting on the first collection day.As a control cohort, we evaluated the data of 151 collections from MM, NHL or Hodgkin lymphoma pts (106 males, 45 females, median age 56y, range 22-74y) with efficient mobilization in response to G-CSF treatment over the same time period.Results: The median concentration of CD34+ cells in PB before & after the first application of plerixafor was 8.4/µl (range 2.9-20.5 /µl) & 23.1/µl (range 10.2-54.1 /µl) respectively, corresponding to a median 3.3-fold increase (range 1.4-5.3-fold, P<0.001, Figure 1). In comparison, pts in the control group had a median concentration of 101.9/µl (range 13-1190/µl) CD34+ cells in PB on the day of stem cell collection (Figure 1).The median CD34+ cell yield for pts receiving plerixafor was 3.7x10^6/kg BW (range 1.6-12.8x10^6/kg BW) compared to 10.5x10^6/kg BW (range 2.1-38.8x10^6/kg BW) in the control cohort (Figure 2).As expected, the WBC count in the product was higher in the plerixafor group (median 899.9x10^8, range 446-2214x10^8) compared to the efficiently mobilizing control cohort (median 470.2x10^8, range 99.9 -1537.1x10^8, P<0.001). The vitality of the cells after thawing was tested with methan blue staining & was comparable in both groups: median 85.3% (range 73.3-92.8%) in the plerixafor group & 84.4% (range 50.6-96.8%) in the control cohort (P=0.242). Furthermore, all harvests were tested for their proliferation capacity by quantifying colony forming units (CFU). Pts receiving plerixafor had a median CFU number of 22.5 (range 1-199), which did not differ from the control cohort with a median of 200.2 CFUs (range 1-1341, P=0.568). To date, 22 (78.6%) of the poorly mobilizing pts have received an autologous stem cell transplantation. All showed good peripheral WBC (median day 11, range 10-15) & platelet (median day 16, range 11-46) recovery.Discussion: Our data shows that addition of plerixafor can increase the efficacy of stem cell harvesting in poor mobilizers. The collected stem cells fulfilled the appropriate quality control criteria including vitality after thawing (>50%) & proliferation capacity. We identified a median 3.3-fold increase in CD34+ cell concentration in PB & a median CD34+ cell yield of 3.7x10^6/kg BW after the application of plerixafor in poor mobilizers. Despite the fact that the CD34+ cell yield in pts receiving plerixafor remained significantly lower than the control cohort, we were able to harvest >2x10^6/kg BW CD34+ cells in 93% (n=26) of poor mobilizers. Thus, the mobilization outcome of pts receiving plerixafor is acceptable and within the expected range. [Display omitted] [Display omitted] DisclosuresFranke:BMS: Honoraria; MSD: Other: Travel Costs; Novartis: Other: Travel Costs. Niederwieser:Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Hematopoietic progenitor cell mobilization with “just-in-time” plerixafor approach is a cost-effective alternative to routine plerixafor use

Background aimsHematopoietic cell mobilization with granulocyte-colony stimulating factor (G-CSF) and plerixafor results in superior CD34+ cell yield compared with G-CSF alone in patients with myeloma and lymphoma. However, plerixafor-based approaches may be associated with high costs. Several institutions use a “just-in-time” plerixafor approach, in which plerixafor is only administered to patients likely to fail mobilization with G-CSF alone. Whether such an approach is cost-effective is unknown. MethodsWe evaluated 136 patients with myeloma or lymphoma who underwent mobilization with 2 approaches of plerixafor utilization. Between January 2010 and October 2012, 76 patients uniformly received mobilization with G-CSF and plerixafor. Between November 2012 and June 2014, 60 patients were mobilized with plerixafor administered only to those patients likely to fail mobilization with G-CSF alone. ResultsThe routine plerixafor group had a higher median peak peripheral blood CD34+ cell count (62 versus 29 cells/μL, P < 0.001) and a higher median day 1 CD34+ yield (2.9 × 106 CD34+ cells/kg versus 2.1 × 106 CD34+ cells/kg, P = 0.001). The median total CD34+ collection was higher with routine plerixafor use (5.8 × 106 CD34+ cells/kg versus 4.5 × 106 CD34+ cells/kg, P = 0.007). In the “just-in-time” group, 40% (n = 24) completed adequate collection without plerixafor. There was no difference in mobilization failure rates. The mean plerixafor doses used was lower with “just-in-time” approach (1.3 versus 2.1, P = 0.0002). The mean estimated cost in the routine plerixafor group was higher (USD 27,513 versus USD 23,597, P = 0.01). DiscussionOur analysis demonstrates that mobilization with a just-in-time plerixafor approach is a safe, effective, and cost-efficient strategy for HPC collection.

Additional plerixafor to granulocyte colony-stimulating factors for haematopoietic stem cell mobilisation for autologous transplantation in people with malignant lymphoma or multiple myeloma

Autologous stem cell transplantation is widely used to restore functioning bone marrow in people with malignant lymphoma or multiple myeloma after myeloablative chemotherapy. Results of some clinical trials indicate that plerixafor in addition to granulocyte colony-stimulating factors (G-CSF) compared to G-CSF only could lead to an increased mobilisation and release of CD34-positive cells, facilitating effective apheresis. To evaluate the efficacy and safety of additional plerixafor to G-CSF for haematopoietic stem cell mobilisation in people with malignant lymphoma or multiple myeloma. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (from 1990 to September 2015), as well as conference proceedings (American Society of Hematology; American Society of Clinical Oncology; European Hematology Association; American Society for Blood and Marrow Transplantation; European Group for Blood and Marrow Transplantation) for studies. Two review authors independently screened search results. We included randomised controlled trials (RCTs) comparing plerixafor in addition to G-CSF compared to G-CSF only for stem cell mobilisation in people with malignant lymphoma or multiple myeloma of all stages and ages. We included full text as well as abstracts and unpublished data if sufficient information on study design, participant characteristics, interventions, and outcomes was available. We excluded cross-over trials, quasi-randomised trials, and post-hoc retrospective trials. Two review authors independently screened the results of the search strategies, extracted data, assessed quality, and analysed data according to standard Cochrane methods. We performed final interpretation with an experienced clinician. We identified four RCTs fitting the inclusion criteria. However, two of these closed prematurely due to low recruitment and did not report results. The remaining two trials evaluated 600 participants with multiple myeloma or non-Hodgkin lymphoma. In both studies the experimental group received G-CSF plus plerixafor and the control group received G-CSF plus placebo.The meta-analysis showed no evidence for differences between plerixafor and placebo group regarding mortality at 12 months (600 participants; risk ratio (RR) 1.00, 95% confidence interval (CI) 0.59 to 1.69; P = 1.00; moderate-quality evidence) and adverse events during stem cell mobilisation and collection (593 participants; RR 1.02, 95% CI 0.99 to 1.06; P = 0.19; high-quality evidence).Regarding the outcome successful stem cell collection, the meta-analysis showed an advantage for those participants randomised to the plerixafor group (600 participants; RR 2.42, 95% CI 1.98 to 2.96; P < 0.00001; high-quality evidence).As there was high heterogeneity between studies for the number of transplanted participants, we did not meta-analyse these data. In the multiple myeloma study, 95.9% (142 participants) in the plerixafor arm and 88.3% (136 participants) in the placebo arm underwent transplantation (RR 1.09, 95% CI 1.02 to 1.16); in the non-Hodgkin lymphoma trial, 90% (135 participants) in the plerixafor group versus 55.4% (82 participants) in the placebo group could be transplanted (RR 1.62, 95% CI 1.39 to 1.89). In both trials there was no evidence for a difference between participants in the plerixafor and placebo group in terms of time to neutrophil and platelet engraftment in transplanted participants.None of the trials reported on the outcomes quality of life and progression-free survival. The results of the analysed data suggest that additional plerixafor leads to increased stem cell collection in a shorter time. There was insufficient evidence to determine whether additional plerixafor affects survival or adverse events.The two trials included in the meta-analysis, both of which were conducted by the Genzyme Corporation, the manufacturer of plerixafor, were published several times. Two more RCTs examining the addition of plerixafor to a G-CSF mobilisation regimen terminated early without publishing any outcome. The trials included nine and five participants, respectively. Another RCT with 100 participants was recently completed, but has not yet published outcomes. Due to the unpublished RCTs, it is possible that our review is affected by publication bias, even though two trials failed to recruit a sufficient number of participants to analyse any data.

Stem Cell Graft Cellular Composition, Hematological and Immune Recovery in NHL Patients Mobilized with or without Plerixafor: A Prospective Comparison

Introduction:Plerixafor, a reversible CXCR4 antagonist, may be used to enhance mobilization of CD34+ cells after G-CSF or chemotherapy plus G-CSF. There is a paucity of prospective data regarding cellular composition of grafts collected after plerixafor in chemomobilized patients. Also the data concerning hematopoietic or immune recovery after high-dose chemotherapy in plerixafor treated lymphoma patients is limited.Patients and methods:Thirty-one patients with NHL were included into this prospective study. There were 14 males and 17 females with a median age of 62 years (range 19 - 73). Altogether fourteen patients received plerixafor (plerixafor group) for poor or late mobilization whereas 17 did not (control group). All patients were mobilized with chemotherapy plus G-CSF. Cryopreserved graft samples were analyzed with flow cytometry for T and B cells (CD3/CD8/CD45/CD19) as well as for NK cells (CD3/CD16+CD56). Also CD34+ cell subclasses were analyzed (CD34/CD38/CD133). Complete blood counts were evaluated at +15 days, 1, 3, 6 and 12 months post-transplant. To evaluate immune reconstitution, flow cytometry of lymphocyte subsets (T, B, NK) was performed at 1, 3 and 6 months after the graft infusion with the same antibody panel as for graft analysis.Results:The median number of infused viable CD34+ cells was higher in the control group (3.1 x 106/kg vs. 2.0 x 106/kg, p = 0.036) (Table 1). The median percentage of the most primitive stem cells (CD34+CD133+CD38-) in the grafts was higher in the plerixafor group (3.5 % vs 1.2 %, p = 0.001), but there was no significant difference in the absolute counts (0.07 x 106/kg vs 0.05 x 106/kg, p = 0.620). The median amounts of CD3+CD4+ and CD3+CD8+ T cell subsets, CD3+ and NK (CD3-CD16/56+) cells were all significantly higher in the plerixafor group (Table 1).The neutrophil counts at +15 days after the graft infusion were lower in the plerixafor group (2.1 x 109/l vs. 4.8 x 109/l, p = 0.013). Otherwise there was no significant difference in the hematological reconstitution between the groups. The immune reconstitution was comparable except for the higher number of NK cells in the plerixafor group at one month (0.4 x 109/l vs. 0.1 x 109/l, p = 0.001). Also a trend towards faster recovery of blood CD4+ T cells was observed after one month in the plerixafor group (0.2 x 109/l vs. 0.1 x 109/l, p = 0.097).Conclusions:This prospective study evaluating cellular composition of grafts confirms that the apheresis products collected from plerixafor-treated NHL patients contain a greater proportion of the more primitive stem cells and a greater number of T lymphocytes and NK cells compared to patients mobilized without plerixafor. Hematopoietic reconstitution was comparable between the groups except for slower neutrophil recovery in the plerixafor-group. Immune reconstitution was comparable but NK cell as well as CD4+ T cell recovery was faster in the plerixafor group. These results will be further evaluated in a larger set of patients. Also the possible effect of graft composition on the progression free and overall survival will be evaluated in the ongoing GOA (Graft and Outcome in Autologous transplantation) study.Table 1Cellular composition of freezed grafts of NHL patients mobilized with or without plerixafor.Mobilization with plerixafor (n = 14)Mobilization without plerixafor (n = 17)P - valueBlood graft analysis (x106/kg)CD34 w/a 7AADCD34 w 7AADCD34+CD38-Proportion of CD34+ CD133+CD38- cells from all CD34+ cells (%)CD3+CD4+CD8+CD19+NK2.1 (0.8 – 5.3)2.0 (0.6 – 5.5)0.07 (0.01 – 0.17)3.5 (0.80 – 10.80)178.3 (49.2 – 454.4)82.1 (29.1 – 267.1)75.4 (16.5 – 279.1)0.0 (0.0 – 0.0)21.5 (0.4 – 39.5)3.4 (1.9 – 7.2)3.1 (1.5 – 6.7)0.05 (0.11 – 0.18)1.2 (0.44 – 5.3)66.2 (16.6 – 415.4)35.6 (8.0 – 114.3)23.3 (8.4 – 301.8)0.0 (0.0 – 3.2)6.6 (0.6 – 20.7)0,0070.0360.6200.0010.0010.0010.0030.1920.001w = withw/a = without7AAD = 7-Aminoactinomycin D DisclosuresJantunen:Sanofi: Employment.

G-CSF Plus Preemptive Plerixafor Versus Cyclophosphamide Plus G-CSF for Autologous Stem Cell Mobilization in Multiple Myeloma: Effectiveness, Safety and Cost Analysis

Introduction: The optimal stem cell mobilization regimen for patients with multiple myeloma (MM) remains undefined. Most transplant centers use either a chemo-mobilization strategy using cyclophosphamide (CY) and granulocyte-colony stimulating factor (G-CSF) or a steady state strategy using G-CSF alone or with plerixafor in case of mobilization failure. However, very few studies compared efficacy, toxicity and cost-effectiveness of stem cell mobilization with cyclophosphamide (CY) and G-CSF versus G-CSF with preemptive plerixafor. In this study, we retrospectively compared our single center experience at the American University of Beirut in 89 MM patients using fractionated high-dose CY and G-CSF as our past preferred chemo-mobilization strategy in MM patients with our new mobilization strategy using G-CSF plus preemptive plerixafor. The change in practice was implemented when plerixafor became available, in order to avoid CY associated toxicity.Patients and methods: Patients in the CY group (n=62) (Table 1) received either fractionated high-dose CY (n=56) (5g/m2 divided in 5 doses of 1g/m2 every 3 hours) or CY at 50mg/kg/day for 2 doses (n=6). G-CSF was started on day +6 of chemotherapy at a fixed dose of 300 µg subcutaneously every 12 hours. All patients in the plerixafor group (n=27) (Table 1) received G-CSF at a fixed dose of 300 µg subcutaneously every 12 hours daily for 4 days. On day 5, if peripheral blood CD34+ was ≥ 20/µl, apheresis was started immediately. Plerixafor (240 µg/kg) was given 7-11 hours before the first apheresis if CD34+ cell count on peripheral blood on day 5 was <20/µl and before the second apheresis if CD34+ cells on the first collect were <3х106/kg. The median number of prior therapies was 1 (range: 1-3) in both groups.Results: Compared with plerixafor, CY use was associated with higher median peak peripheral blood CD34+ counts (35 vs 111 cells/µl, P= 0.000003), and total CD34+ cell yield (7.5 х 106 vs 15.9 х 106 cells/kg, P= 0.003). All patients in both groups collected ≥4x106 CD34+ cells/Kg. Moreover, 60 (96.7%) and 46 (74.2%) patients in the CY group vs 24 (88.8%) and 6 (22%) patients in the plerixafor group collected >6х106 and >10x106 CD34+ cells/kg, respectively (P=0.16; P<0.00001). Only 4 (6.4%) patients required two apheresis sessions in the CY group compared to 11 (40%) in the plerixafor group (P=0.0001). Conversely, CY use was associated with higher frequency of febrile neutropenia (60% vs 0%; P<0.00001), blood transfusions (27% vs 0%; P<0.00001), platelets transfusion (25% vs 0%; P<0.00001) and hospitalizations (64% vs 0%; P<0.00001). No one required intensive level of care and all recovered. Autografting was successfully performed in all patients using high-dose melphalan with a median time from mobilization to the first transplant of 31 days (range: 16-156) in the CY group compared to 13 days (range: 8-40) in the plerixafor group (P=0.027); and median infused CD34+ cells were 7х106/kg (range: 3.1-15.3) versus 5.27 (2.6-7.45), respectively (P=0.002). The average total cost of mobilization using the adjusted costs based on National Social Security Fund (NSSF) prices in Lebanon in the plerixafor group was slightly higher compared with the CY group ($7964 vs $7536; P=0.16).Conclusions: Our data indicate robust stem cell mobilization in MM patients with either fractionated high-dose CY and G-CSF or G-CSF alone with preemptive plerixafor. The chemo-mobilization approach was associated with two-fold stem cell yield, slightly lower cost (including cost of hospitalization) but significantly increased toxicity. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Superior long-term repopulating capacity of G-CSF+plerixafor-mobilized blood: implications for stem cell gene therapy by studies in the Hbb(th-3) mouse model.

High numbers of genetically modified hematopoietic stem cells (HSCs) equipped with enhanced engrafting potential are required for successful stem cell gene therapy. By using thalassemia as a model, we investigated the functional properties of hematopoietic stem and progenitor cells (HSPCs) from Hbb(th3)/45.2(+) mice after mobilization with G-CSF, plerixafor, or G-CSF+plerixafor and the engraftment kinetics of primed cells after competitive primary and noncompetitive secondary transplantation. G-CSF+plerixafor yielded the highest numbers of HSPCs, while G-CSF+plerixafor-mobilized Hbb(th3)/45.2(+) cells, either unmanipulated or transduced with a reporter vector, achieved faster hematologic reconstitution and higher levels of donor chimerism over all other types of mobilized cells, after competitive transplantation to B6.BoyJ/45.1(+) recipients. The engraftment benefit observed in the G-CSF+plerixafor group was attributed to the more primitive stem cell phenotype of G-CSF+plerixafor-LSK cells, characterized by higher CD150(+)/CD48 expression. Moreover, secondary G-CSF+plerixafor recipients displayed stable or even higher chimerism levels as compared with primary engrafted mice, thus maintaining or further improving engraftment levels over G-CSF- or plerixafor-secondary recipients. Plerixafor-primed cells displayed the lowest competiveness over all other mobilized cells after primary or secondary transplantation, probably because of the higher frequency of more actively proliferating LK cells. Overall, the higher HSC yields, the faster hematological recovery, and the superiority in long-term engraftment indicate G-CSF+plerixafor-mobilized blood as an optimal graft source, not only for thalassemia gene therapy, but also for stem cell gene therapy applications in general.

Pharmacoeconomic impact of up-front use of plerixafor for autologous stem cell mobilization in patients with multiple myeloma

Background aimsStem cell collection can be a major component of overall cost of autologous stem cell transplantation (ASCT). Plerixafor is an effective agent for mobilization; however, it is often reserved for salvage therapy because of its high cost. We present data on the pharmacoeconomic impact of the use of plerixafor as an up-front mobilization in patients with multiple myeloma (MM). MethodsPatients with MM who underwent ASCT between January 2008 and April 2011 at the Mount Sinai Medical Center were reviewed retrospectively. In April 2010, practice changes were instituted for patients with MM to delay initiation of granulocyte-colony-stimulating factor (G-CSF) support from day 0 to day +5 and to add plerixafor to G-CSF as an up-front autologous mobilization. Targets of collection were 5–10 × 106 CD34+ cells/kg. ResultsOf 50 adults with MM who underwent ASCT, 25 received plerixafor/filgrastim and 25 received G-CSF alone as an up-front mobilization. Compared with the control, plerixafor mobilization yielded higher CD34+ cell content (16.1 versus 8.4 × 106 CD34+ cells/kg; P = 0.0007) and required fewer sessions of apheresis (1.9 versus 3.1; P = 0.0001). In the plerixafor group, the mean number of plerixafor doses required per patient was 1.8. Although the overall cost of medications was higher in the plerixafor group, the cost for blood products and overall cost of hospitalization were similar between the two groups. ConclusionsUp-front use of plerixafor is an effective mobilization strategy in patients with MM and does not have a substantial pharmacoeconomic impact in overall cost of hospitalization combined with the apheresis procedure.

Rescue stem cell mobilization with plerixafor economizes leukapheresis in patients with multiple myeloma.

While extensive data demonstrated that plerixafor improves stem cell harvest in difficult-to-mobilize patients, economic concerns limit a broader application. We retrospectively assessed the effect of an early plerixafor rescue regimen for mobilization in patients with multiple myeloma. Patients were intended for high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (ABSCT) and therefore received cyclophosphamide-based mobilization chemotherapy and consecutive stimulation with granulocyte colony-stimulating factor (G-CSF). Fifteen patients with poor stem cell harvest in the first leukapheresis session received plerixafor. Data were compared with a matched historic control group of 45 patients who also had a poor stem cell yield in the first apheresis session, but continued mobilization with G-CSF alone. Patients in the plerixafor group collected significantly more CD34+ cells in total (median 4.9 vs. 3.7 [range 1.6-14.1 vs. 1.1-8.0] × 10(6) CD34+ cells /kg bw; P < 0.05), and also more CD34+ cells per leukapheresis procedure (P < 0.001). Consequently, they required a significantly lower number of leukapheresis procedures to achieve the collection goal (median 2.0 vs. 4.0 [range 2-3 vs. 2-9] procedures; P < 0.001). The efficiency of the collected stem cells in terms of hematologic engraftment after ABSCT was found to be equal in both groups. These data demonstrate that rescue mobilization with plerixafor triggered by a low stem cell yield in the first leukapheresis session is effective. Although the actual economic benefit may vary depending on the local leukapheresis costs, the median saving of two leukapheresis procedures offsets most of the expenses for the substance in this setting. An exemplary cost calculation is provided to illustrate this effect.

Utility Of An Algorithm For Use Of Plerixafor In Filgrastim-based Hematopoietic Progenitor Cell Mobilization In Patients With Plasma Cell Myeloma Treated With Carfilzomib-Lenalidomide-Dexamethasone.

▪Mobilization of hematopoietic progenitor cells (HPC) for subsequent autologous transplantation is difficult in patients with plasma cell myeloma (PCM) due to poor marrow reserve. Targeted HPC yields are generally not achieved in a single apheresis procedure without use of plerixafor as a supplement to standard filgrastim. Strategies to limit use of plerixafor, due to its expense, to cases of poor CD34 mobilization have been developed, but their applicability in patients receiving the novel induction regimen carfilzomib-lenalidomide-dexamethasone (CRD) (Blood 2012;120:1801) has not been described. We prospectively studied the CD34 cell mobilization responses of PCM patients following CRD induction, using a CD34 cell predictive algorithm to determine when plerixafor should be added to the mobilization regimen. Thirty patients, including 23 with PCM and 7 with smoldering PCM, mean age 55 (range 40-72), 47% male, received 4 to 7 cycles of CRD (median, 5 cycles), with the last dose of lenalidomide given at least one week prior to mobilization. Filgrastim 10-16 mcg/kg/day was given as a single evening dose for 5 days, with circulating CD34 count assessed 12 hours after the 4th dose. The pre-apheresis CD34 count after the 5th dose of filgrastim was predicted to be 10% greater than that after the 4th dose; this prediction was validated with an actual pre-apheresis CD34 count obtained the following day. Prior mobilization data derived from healthy HPC apheresis donors was used to generate a regression formula, y=0.45x+0.86, where x=the pre-apheresis circulating CD34 count after the 5th dose of filgrastim, and y=the expected yield of the apheresis procedure, expressed as millions of CD34 cells harvested per liter processed. Targeted yield was ≥ 4 x 106 CD34 cells/kg, with minimum acceptable yield ≥ 2 x 106 CD34 cells/kg. Plerixafor 240 mcg/kg was given with the 5th dose of filgrastim, 8-10 hours prior to apheresis, if the regression equation predicted a CD34 cell yield of < 4 x 106 CD34 cells/kg in a single procedure with a maximum of 30 liters processed. The actual volume processed was based on the stat blood CD34 count drawn immediately prior to apheresis. Procedures were performed on the Cobe Spectra device; continuous intravenous calcium was used to mitigate citrate toxicity. Central lines were required in 67% of subjects.Mean CD34 cell count in the entire group after the 4th dose of filgrastim was 29/uL (range 2-88/uL). Using the regression formula as a guide, 17/30 (57%) of patients received plerixafor. CD34 counts increased 4.2-fold in patients receiving plerixafor, from 15 ± 9/uL (m ± SD) on the day prior to apheresis to 53 ± 30/uL immediately pre-apheresis; CD34 counts did not change in patients who received filgrastim alone (from 48 ± 17/uL to 45 ± 19/uL). Guided by the stat pre-apheresis CD34 count, the volume processed in the first apheresis procedure was the same, 23 ± 7 (range 12-30) liters, with or without plerixafor. CD34 cells were collected with 72 ± 14% efficiency. First-procedure CD34 cell yields were 6.4 ± 2.5 x 106/kg (range 2.5-10.1) with supplemental plerixafor vs 5.8 ± 2.5 x 106/kg (range 1.1-9.3) with filgrastim alone. Only 2/30 patients underwent a second procedure; neither received plerixafor prior to the first procedure, and both received it prior to the second. In one patient, criteria for plerixafor administration were met, but the drug was inadvertently not given prior to the first procedure; in the second patient, an unexpectedly low pre-apheresis CD34 count was traced to inadequate self-administration of the 5th dose of filgrastim. All 30 patients achieved the minimum CD34 collection goal of ≥ 2 x 106 cells/kg and 29/30 did this in one procedure. The higher targeted collection goal of ≥ 4 x 106 CD34 cells/kg was achieved in a single procedure by 76% of patients in both the plerixafor group and the filgrastim-alone group. There was a trend for higher cumulative lenalidomide and carfilzomib doses to be associated with lower CD34 mobilization responses to filgrastim.Induction treatment with CRD does not appear to impair HPC mobilization response to filgrastim in patients with PCM, compared to older regimens. An algorithm that uses the CD34 cell count after 4 doses of filgrastim to predict the following day's pre-apheresis CD34 count and thus determine whether plerixafor supplementation is needed, was useful in identifying the 40% of CRD-treated myeloma patients who do not need plerixafor. Disclosures:No relevant conflicts of interest to declare.

Engraftment and outcome after autologous stem cell transplantation in plerixafor‐mobilized non‐Hodgkin's lymphoma patients

Plerixafor is used in combination with granulocyte-colony-stimulating factor to enhance the mobilization of hematopoietic stem cells. Limited data are available in regard to effects of plerixafor on posttransplant outcomes in chemomobilized patients who appear to mobilize poorly. Eighty-nine chemomobilized patients with non-Hodgkin's lymphoma (NHL) were included in this retrospective study. Thirty-three patients had received plerixafor preemptively (plerixafor group) and 56 patients served as controls. Posttransplantation outcomes including infections, hematologic recovery, and relapse were recorded. The median fold increase of CD34+ cells after the first plerixafor dose was 4.1 in patients mobilized with chemotherapy plus filgrastim and 7.2 in those mobilized with chemotherapy plus pegfilgrastim (p = 0.027). The median number of collected CD34+ cells was 3.5 × 10(6) CD34+ cells/kg in the plerixafor group and 4.2 × 10(6) CD34+ cells/kg in the control group (p = 0.076). Early engraftment was comparable between the groups (10 days for neutrophils >0.5 × 10(9) /L and 14 days for platelets >20 × 10(9) /L, respectively). Also late engraftment within 12 months was comparable except higher hemoglobin level at 3 months in the control group (121 g/L vs. 112 g/L, p = 0.009). Progression-free survival at 1 year after autologous stem cell transplantation (ASCT) was 79% in the plerixafor group and 86% in the control group (p = 0.399). Long-term engraftment and outcome after ASCT seem to be comparable in NHL patients receiving plerixafor compared to chemomobilized patients. These observations support the use of plerixafor in patients who mobilize poorly.

Safety and efficacy of upfront plerixafor + G-CSF versus placebo + G-CSF for mobilization of CD34(+) hematopoietic progenitor cells in patients ≥60 and

The efficacy and safety of plerixafor + G-CSF in enhancing hematopoietic stem cell mobilization and collection has been demonstrated in two phase III studies involving patients with NHL or MM. In these pivotal studies, plerixafor + G-CSF significantly increased the proportion of patients achieving target stem cell yields, compared to placebo + G-CSF. In this analysis, we compare the efficacy and safety of plerixafor + G-CSF versus placebo + G-CSF in patients enrolled in the two phase III studies, stratified by age: ≥60 years of age and <60 years of age. The proportion of older patients who achieved target stem cell yields was significantly higher in the plerixafor group than in placebo group (NHL: 50.9 vs. 25.4%, P < 0.001; MM: 69.6 vs. 23.7%, P < 0.001). In this older cohort, the median times to neutrophil and to platelet engraftment following autologous stem cell transplant were comparable between the plerixafor and placebo groups. Similar efficacy findings were observed in the younger age group. The most common adverse events (all grades) reported among older patients in the plerixafor group included diarrhea (41.3%), nausea (38.9%), fatigue (30.2%), and injection-site reaction (29.4%). The frequency of adverse events was similar between the older and the younger age groups. Taken together, our subanalysis demonstrate that plerixafor + G-CSF can be safely and effectively used in adult patients of all ages, including those ≥60 years, to support optimal stem cell mobilization for autologous stem cell transplantation.

Peripheral blood stem cell mobilization in multiple myeloma patients treat in the novel therapy‐era with plerixafor and G‐CSF has superior efficacy but significantly higher costs compared to mobilization with low‐dose cyclophosphamide and G‐CSF

Studies comparing the efficacy and cost of peripheral blood stem and progenitor cells mobilization with low-dose cyclophosphamide (LD-CY) and granulocyte-colony stimulating factor (G-CSF) against plerixafor and G-CSF, in multiple myeloma (MM) patients treated in the novel therapy-era are not available. Herein, we report mobilization outcomes of 107 patients who underwent transplantation within 1-year of starting induction chemotherapy with novel agents. Patients undergoing mobilization with LD-CY (1.5 gm/m(2)) and G-CSF (n = 74) were compared against patients receiving plerixafor and G-CSF (n = 33). Compared to plerixafor, LD-CY was associated with a significantly lower median peak peripheral blood CD34+ cell count (68/µL vs. 36/µL, P = 0.048), and lower CD34+ cell yield on day 1 of collection (6.9 × 10(6)/kg vs. 2.4 × 10(6)/kg, P = 0.001). Six patients (8.1%) in the LD-CY group experienced mobilization failure, compared to none in the plerixafor group. The total CD34+ cell yield was significantly higher in the plerixafor group (median 11.6 × 10(6)/kg vs. 7 × 10(6)/kg; P-value = 0.001). Mobilization with LD-CY was associated with increased (albeit statistically non-significant) episodes of febrile neutropenia (5.4% vs. 0%; P = 0.24), higher use of intravenous antibiotics (6.7% vs. 3%; P = 0.45), and need for hospitalizations (9.4% vs. 3%; P = 0.24). The average total cost of mobilization in the plerixafor group was significantly higher compared to the LD-CY group ($28,980 vs. $19,626.5 P-value < 0.0001). In conclusion, in MM plerixafor-based mobilization has superior efficacy, but significantly higher mobilization costs compared to LD-CY mobilization. Our data caution against the use of LD-CY in MM patients for mobilization, especially after induction with lenalidomide-containing regimens.

Comparable efficacy and lower cost of PBSC mobilization with intermediate-dose cyclophosphamide and G-CSF compared with plerixafor and G-CSF in patients with multiple myeloma treated with novel therapies

Studies comparing the efficacy and cost of stem cell mobilization with intermediate-dose CY (ID-CY) and G-CSF against plerixafor and G-CSF, specifically in multiple myeloma (MM) patients treated in the novel therapy era, are not available. Eighty-eight consecutive patients undergoing mobilization with ID-CY (3-4 g/m(2)) and G-CSF (n=55) were compared with patients receiving plerixafor and G-CSF (n=33). Compared with plerixafor, ID-CY use was associated with higher median peak peripheral blood CD34+ cell count (68 vs 160 cells/μL, P<0.001), and CD34+ cell yield on day 1 of collection (6.9 × 10(6) vs 11.7 × 10(6) cells/kg, P<0.001). Total CD34+ cell yield was significantly higher in the ID-CY patients (median collection 16.6 × 10(6) vs 11.6 × 10(6) cells/kg; P<0.001). ID-CY use was associated with significantly more frequent episodes of febrile neutropenia (16.3% vs 0%; P=0.02), intravenous antibiotic use (16.3% vs 3%; P=0.03) and hospitalizations (P=0.02). The average total cost of mobilization in the plerixafor group was significantly higher compared with the ID-CY group ($28 980 vs $22 504.8; P=0.001). Our data indicate robust stem cell mobilization in MM patients treated with novel agents, with G-CSF and either ID-CY or plerixafor. When compared with plerixafor, ID-CY-containing mobilization was associated with significantly lower average total mobilization costs.

Comparison of Post-Transplant Outcomes in Non-Hodgkin Lymphoma (NHL) Patients Mobilized with or without Plerixafor Added to Chemomobilization

Abstract 4520 Background:Plerixafor, a CXCR4 antagonist, is used in a combination with G-CSF with or without chemotherapy to enhance mobilization of hematopoietic stem cells (CD34+) from the bone marrow to circulation. Prior studies have shown that plerixafor may mobilize more primitive stem cells and also have impact on other cell populations too. These changes may have impact in engraftment, immunological reconstitution and post-transplant outcome. However, only limited data are available in regard to effects of plerixafor in post-transplant outcomes. Patients and methods:Eighty-nine patients with non-Hodgkin lymphoma (NHL) were included in this study. The patients received disease-specific chemomobilization (most commonly cytarabine based) with G-CSF. In addition, 33 patients (37 %) received plerixafor because of insufficient mobilization, poor collection yields or late mobilization (plerixafor group). Fifty-six patients served as controls (control group). The median age was 58 years in the plerixafor group and 57 years in the control group (p=0.515). The most common histology was diffuse large B-cell lymphoma in both groups. The proportion of patients beyond CR1 or PR1 was significantly higher (55 % vs. 32%, p=0.046) in the plerixafor group. All patients were treated with a single dose (6 mg) of pegfilgrastim after stem cell infusion. Patients were followed after high-dose chemotherapy in regard to haematopoietic engraftment and outcome. Results:The median amount of collected CD34+ cells was 3.5 × 106 CD34+ cells/kg (range 1.3 – 8.9 × 106 CD34+ cells/kg) in the plerixafor group and 4.2 × 106 CD34+ cells/kg (range 1.9 – 18.6 × 106 CD34+ cells/kg) in the control group (p=0.076). The median number of aphaeresis was two (range 1–5) in both groups (p=0.17). The median neutrophil engraftment was 10 days in both groups (range 8–81 days in the plerixafor group and 8–21 days in the control group). The median time to platelet engraftment was 14 days in both groups (range 10–165 days in the plerixafor group and 10–91 days in the control group). The incidence of neutropenic fever was comparable between the groups (71% vs. 76%, p=0.906). The median follow-up time from ASCT was 373 days (range 5–929 days) in the plerixafor group and 518 days (range 81–1175 days) in the control group (p=0.052). No difference in counts of haemoglobin, leucocytes, lymphocytes or platelets were observed at +1, +3, +6, +12 months except for haemoglobin which was significantly higher in the plerixafor group at +3 months. Progression-free survival (PFS) was 72 % in the plerixafor group and 75 % in the control group (p=0.69). Overall survival (OS) was also comparable between the groups (82 % vs. 84 %, p=0.67). Conclusions:The recovery from ASCT and outcome after ASCT seems to be comparable in lymphoma patients whether plerixafor is used or not. Prospective studies including more detailed characterisation of graft cellular content in regard to CD34+ cell subtypes, T-cell repertoire and NK-cells are needed to assess the impact of mobilization method post-transplant outcome. Disclosures:Jantunen:Genzyme: Has participated in EU Leadership meeting organized by Genzyme as well as Medical Advisory Board meeting organized by Genzyme Other, Honoraria.

Blood graft composition after plerixafor injection in patients with NHL

Plerixafor is used to mobilize CD34(+) hematopoietic stem cells from bone marrow to circulation. Limited data are available in regard to graft cellular content collected after plerixafor. The aim of this study was to assess effects of plerixafor added to chemomobilization on graft CD34(+) cell subclasses, lymphocyte subsets, engraftment, and post-transplant course in non-Hodgkin lymphoma (NHL) patients. Thirty-four patients with NHL were included. All patients received chemotherapy plus G-CSF to mobilize stem cells. Nineteen patients received plerixafor pre-emptively owing to poor mobilization or poor collection yields. The rest of the patients constituted the control group. Flow cytometric analyzes were performed from cryopreserved graft samples. Also, data on post-transplant engraftment and outcome were collected. The proportion of primitive stem cells (CD34(+) CD133(+) CD38(-) ) was significantly higher after the plerixafor injection when compared to the first collection in the control group. The amount of T cells (CD3(+) ), helper (CD3(+) CD4(+) ) T subsets, and suppressor (CD3(+) CD8(+) ) T subsets in the graft was all significantly higher in the plerixafor group. Also, the amount of NK cells (CD3(-) CD16/56(+) ) was higher. Engraftment after high-dose therapy was comparable between the groups, but leukocyte and platelet count at 6months were higher in patients receiving plerixafor-mobilized grafts. Plerixafor, when used pre-emptively in addition to chemomobilization, seems to mobilize more primitive CD34(+) stem cells, T lymphocytes, and NK cells. Whether these differences are associated with immune reconstitution, long-term engraftment, or patient outcomes needs to be evaluated in larger patient groups with longer follow-up.

Pharmacoeconomic Impact of Upfront Use Plerixafor for Autologous Stem Cell Mobilization in Multiple Myeloma Patients

Abstract 2075 The most commonly employed agent for upfront stem cell mobilization is granulocyte-colony-stimulating factor (G-CSF), which is associated with about 25% of unsuccessful mobilization. Plerixafor was granted FDA approval based on improved rate of successful mobilization as an upfront mobilizing agent. However, because of its cost, it is often reserved for patients who failed previous standard mobilization. This strategy can increase the number of apheresis and potentially delay treatment. This retrospective study, performed between January 2008 and April 2011, included 50 adult patients with multiple myeloma (MM) who underwent ASCT. Twenty-five patients received plerixafor, in combination with G-CSF, and 25 patients received G-CSF alone as an upfront mobilization therapy. Plerixafor was given as 0.24mg/kg/day SC in the evening for up to 4 days, starting on day 4 of G-CSF. For stem cell collection, G-CSF was given as 10mcg/kg/day SC in the morning for 5 days. Targets of collection were minimal 5 x106 and optimal 107 CD34+ cells/kg. After ASCT, G-CSF was given as 5mcg/kg/day IV from day 0 until engrafted. In April 2010, a practice change was instituted to delay initiation of G-CSF from day 0 to day +5 following ASCT. Simultaneously, plerixafor was used, in combination with G-CSF, as an upfront mobilization therapy for autologous stem cell mobilization in MM patients. The primary objective of this study was to assess pharmacoeconomic impact of using plerixafor as an upfront mobilization therapy in patients with MM. There were no differences in age (mean, 57.4±8.7 yrs vs. 56.4±6.3 yrs; p=NS), weight (mean, 74.6±15.9kg vs. 75±19.7kg; p=NS), number of previous SCT (mean, 0±0.2 vs. 0.1±0.3; p=NS), patients with relapsed disease (16% vs. 16%; p=NS) or melphalan dose (mean, 192.8±19.9mg vs. 192.8 ±19.9mg; p=NS) between plerixafor group and the control. Compared with the control, plerixafor mobilizations yielded higher CD34+ cell content [mean (x106 CD34+ cells/kg), 16.1±9.7 vs. 8.4±4.6; p=0.0007], higher number of CD 34+cells infused [mean (x106 CD34+ cells/kg), 7.6±4.6 vs. 4.4±1.7; p=0.0017], required fewer number of G-CSF doses for both stem cell collection (mean, 5.9±1.1 vs. 7.1±1; p=0.0001) and for neutrophil recovery (mean, 8±1.8 vs. 11.8±1.1; p<0.0001), and required fewer number of apheresis (mean, 1.9±1.1 vs. 3.1±1; p=0.0001). The plerixafor group had a longer time to neutrophil engraftment compared with the control (mean, 10.8±0.9 days vs. 9.8±0.9 days; p<0.0001); however, this did not translated to longer days of hospitalization post-ASCT (mean, 15.2±2.7 days vs. 14.1±3.1 days; p=NS). The plerixafor group required fewer G-CSF doses for both mobilization and neutrophil recovery, and fewer apheresis sessions. Therefore, this group had a lower cost of G-CSF per patient for both stem cell collection (mean, $2,212±572 vs. $2,765±487, p=0.0006) and for stem cell recovery (mean, $1,677±521 vs. $2,653±1,125, p=0.0003), and also lower cost of apheresis per patient (mean, $889±517 vs. $1,476±479; p=0.0001). The mean number of plerixafor doses per patient was 1.8±1, with a cost per patient of $9,081.6±5,220. Based on our interim data for overall cost analysis, the plerixafor group had similar cost for blood products per patient (mean, $2,803±3,049 vs. $2,332±1,160, p=0.49), overall cost of medications (mean, $19,461±5,307 vs. $22,442±5,451, p=0.13), overall cost of hospitalization (mean, $60,646±13,981 vs. $61,474±10,464, p=0.84), and cost of hospitalization and apheresis combined per patient (mean, $61,632±14,163 vs. $62,949±10,298, p=0.75). This data suggests that using plerixafor for upfront autologous stem cell mobilization in patients with MM significantly improves success rate of mobilization, decreases the number of apheresis sessions, and does not have a substantial pharmacoeconomic impact. Disclosures: No relevant conflicts of interest to declare.

Pharmacoeconomic Impact of Upfront Use Plerixafor for Autologous Stem Cell Mobilization in Multiple Myeloma Patients

Abstract 2075The most commonly employed agent for upfront stem cell mobilization is granulocyte-colony-stimulating factor (G-CSF), which is associated with about 25% of unsuccessful mobilization. Plerixafor was granted FDA approval based on improved rate of successful mobilization as an upfront mobilizing agent. However, because of its cost, it is often reserved for patients who failed previous standard mobilization. This strategy can increase the number of apheresis and potentially delay treatment.This retrospective study, performed between January 2008 and April 2011, included 50 adult patients with multiple myeloma (MM) who underwent ASCT. Twenty-five patients received plerixafor, in combination with G-CSF, and 25 patients received G-CSF alone as an upfront mobilization therapy. Plerixafor was given as 0.24mg/kg/day SC in the evening for up to 4 days, starting on day 4 of G-CSF. For stem cell collection, G-CSF was given as 10mcg/kg/day SC in the morning for 5 days. Targets of collection were minimal 5 x106 and optimal 107 CD34+ cells/kg. After ASCT, G-CSF was given as 5mcg/kg/day IV from day 0 until engrafted. In April 2010, a practice change was instituted to delay initiation of G-CSF from day 0 to day +5 following ASCT. Simultaneously, plerixafor was used, in combination with G-CSF, as an upfront mobilization therapy for autologous stem cell mobilization in MM patients. The primary objective of this study was to assess pharmacoeconomic impact of using plerixafor as an upfront mobilization therapy in patients with MM. There were no differences in age (mean, 57.4±8.7 yrs vs. 56.4±6.3 yrs; p=NS), weight (mean, 74.6±15.9kg vs. 75±19.7kg; p=NS), number of previous SCT (mean, 0±0.2 vs. 0.1±0.3; p=NS), patients with relapsed disease (16% vs. 16%; p=NS) or melphalan dose (mean, 192.8±19.9mg vs. 192.8 ±19.9mg; p=NS) between plerixafor group and the control. Compared with the control, plerixafor mobilizations yielded higher CD34+ cell content [mean (x106 CD34+ cells/kg), 16.1±9.7 vs. 8.4±4.6; p=0.0007], higher number of CD 34+cells infused [mean (x106 CD34+ cells/kg), 7.6±4.6 vs. 4.4±1.7; p=0.0017], required fewer number of G-CSF doses for both stem cell collection (mean, 5.9±1.1 vs. 7.1±1; p=0.0001) and for neutrophil recovery (mean, 8±1.8 vs. 11.8±1.1; p<0.0001), and required fewer number of apheresis (mean, 1.9±1.1 vs. 3.1±1; p=0.0001). The plerixafor group had a longer time to neutrophil engraftment compared with the control (mean, 10.8±0.9 days vs. 9.8±0.9 days; p<0.0001); however, this did not translated to longer days of hospitalization post-ASCT (mean, 15.2±2.7 days vs. 14.1±3.1 days; p=NS). The plerixafor group required fewer G-CSF doses for both mobilization and neutrophil recovery, and fewer apheresis sessions. Therefore, this group had a lower cost of G-CSF per patient for both stem cell collection (mean, $2,212±572 vs. $2,765±487, p=0.0006) and for stem cell recovery (mean, $1,677±521 vs. $2,653±1,125, p=0.0003), and also lower cost of apheresis per patient (mean, $889±517 vs. $1,476±479; p=0.0001). The mean number of plerixafor doses per patient was 1.8±1, with a cost per patient of $9,081.6±5,220. Based on our interim data for overall cost analysis, the plerixafor group had similar cost for blood products per patient (mean, $2,803±3,049 vs. $2,332±1,160, p=0.49), overall cost of medications (mean, $19,461±5,307 vs. $22,442±5,451, p=0.13), overall cost of hospitalization (mean, $60,646±13,981 vs. $61,474±10,464, p=0.84), and cost of hospitalization and apheresis combined per patient (mean, $61,632±14,163 vs. $62,949±10,298, p=0.75).This data suggests that using plerixafor for upfront autologous stem cell mobilization in patients with MM significantly improves success rate of mobilization, decreases the number of apheresis sessions, and does not have a substantial pharmacoeconomic impact. Disclosures:No relevant conflicts of interest to declare.

The Outcome of Autologous Stem Cell Transplantation and the Risk of Relapse in Myeloma and Lymphoma Patients Mobilized Using Plerixafor Compared to Standard Mobilization Regimen

Abstract 4399Autologous stem cell transplantation (ASCT) is a method of choice in many hematological malignancies enabling the patients (pts) to achieve remission or to prolong life. Commonly used mobilizing regimens include high dose chemotherapy followed by G-CSF administration. Unfortunately up to 35% pts fail to mobilize the successful number of stem cells (SC).16 pts aged 48 (23–69) were mobilized with plerixafor in our clinic over one-year period. All of the them failed to mobilize to collect satisfactory number of SC after standard mobilizing regimen. The protocol included G-CSF (10μg/kg) administered subcutaneously for 4 days, followed by plerixafor administration (240μg/kg s.c.). Only two pts failed to collect satisfactory number of SC after plerixafor. 14/16 collected the median of 2.24×106/kg (0.8–15,8), all of them underwent the ASCT. The outcome of ASCT in this group was compared to the posttransplant period in pts mobilized with standard mobilizing regimen (control group; CG).The amount of CD34+cells x106/kg was significantly higher in the CG (2.24 vs. 4.4, p<.05). The proportion of CD34+ cells among total nucleated cells was significantly lower in the plerixafor group compared to the CG (0.22 vs 1.72, p<.004). The high nucleated cell count translated into high volume of SC product (median 1650mL; 800–2800mL). The volume of frozen SC product was significantly higher in the plerixafor group compared to the CG (1650 vs. 800mL, p<.00). The length of hospital stay (median: 26 days in both groups), incidence of serious infections (41% in plerixafor group vs. 40% in the CG), use of i.v. antibiotics (median: 15 vs. 16 days), number of RBC and platelet (PLT) transfusions (median: 2 vs. 3 units for both RBC and PLT), time to ANC engraftment (ANC>0.5G/l) −10 vs. 14 days, and to PLT engraftment (PLT>20G/l) – 11vs. 14 days, were not different significantly. 43% pts relapsed in plerixafor group with a median follow-up of 14 months and 37% pts in the CG with a median follow up of 11 months (p>.05).SC mobilization with plerixafor and G-CSF provides solution for majority of pts requiring ASCT and failing mobilization with G-CSF in combination with chemotherapy. However, due to high leukocytosis, this protocol may require modification of SC collection and freezing procedures in order to avoid large volumes. In general, pts mobilized with plerixafor had similar post transplant outcome as pts who were mobilized using standard regimen. Disclosures:No relevant conflicts of interest to declare.

Plerixafor Ex Vivo Mobilization of Placental Derived Haematopoietic Stem Cells

Abstract 4790 IntroductionThe utility of cord blood as an alternative source of stem cells for haematopoietic stem cell transplantation is well established in the paediatric population. Although it's use in adults has surged over the past few years there are still problems associated with a low stem cell dose which may lead to delayed engraftment, incomplete and inefficient immune reconstitution, and poor survival. Various techniques have been used to increase the stem cell dose including ex vivo expansion, the use of double cords, intrabone injections and the use of third party donor cells. Using standard collection techniques only about 25% of cord blood samples collected reach the target cell dose in adults. The placenta is a rich source of CD34+ cells which may not be fully mobilised using current cord blood collection techniques. A modified two-step collection technique in which the initial collection is followed by placental perfusion with 50 ml heparinised 0.9% saline has shown a 15% increase in the number of nucleated cells. We have modified this technique further by perfusing the placenta with Plerixafor, a CXCR4 antagonist that is currently licensed in the UK for mobilisation of autologous stem cells from adults. The study aim was to assess whether plerixafor could enhance recovery of CD34+ cells and change the immune profile of the perfusate. MethodTen cord blood units were collected as per our standard operating procedures. After cord blood collection, 5 placentas were perfused with 50 ml 0.9% saline plus 5,000 units of preservative free heparin by slow infusion over 50 minutes and perfusate collected after about 5 minutes of starting the infusion over 50 minutes (controls). The other 5 placentas were treated the same way except for the addition of 24 mg Plerixafor to the 50 ml 0.9% saline plus 5,000 units of preservative free heparin and collected as per control arm (plerixafor arm).The samples were analysed by multicolour flow cytometry using a combination of antibody cocktails to identify and enumerate CD34+ stem cells, T cells, T cell precursors, T cell subsets, T regulatory cells, B cells, NK and NK cell precursors, and Dendtritic cells. The CD34+ progenitor cells were further quantified by CFU – a methylcellulose media based assay. ResultsSuccessful recovery of perfusate was achieved from 9 placentas (mean volume 44 ml +/− SEM 4.7) as one of the collected samples clotted. There was no significant difference in the perfusate volumes between the 2 arms (48ml v 38ml, P=0.152). Percentage increase in numbers of cells recovered by perfusing the placenta was calculated from total numbers of CD34+ and CD45+ cells collected from each cord and placenta pair. Plerixafor did not significantly increase the recovery of cells from the placenta. Perfusion of the 5 control placentas increased recovery of CD34+ cell by 5.06% (mean +/− 0.89 SEM) and CD45+ cells by 4.69% (mean +/−1.09 SEM). Perfusion of 4 placentas with saline plus Plerixafor increased recovery of CD34+ cells by 5.79% (mean +/−2.17 SEM) and CD45+ cells by 2.61% (mean +/− 0.79 SEM). Viability of haematopoietic stem cell progenitors was assessed by colony formation assay with no significant difference detected between the control arm (mean 18.4 CFU +/− 8.26 SEM; n=5) and the plerixafor arm (mean 4.8 CFU +/− 2.7 SEM; n=4).There was no significant difference in the number of CD34+ cells recovered from the controls as compared to their corresponding cords (n=5, paired t test, p= 0.054). Similarly, there was no significant difference in the plerixafor arm (n=4, paired t test, p=0.091). There was no significant increase in the number of CD34+ stem cells recovered from the plerixafor group as compared to the control group (unpaired t test, p=0.74). There was no significant increase in the number of CD45+ cells in the plerixafor arm compared to the controls (unpaired t test, p= 0.4). Similarly there was no significant difference in the clonal efficiency of the between the 2 groups (unpaired t test, p=0.2).There were no significant differences in the CD3, CD4, CD8 T cells, Tregs, NK, DCs, progenitor T and NK cells between the 2 groups. ConclusionIn this pilot study plerixafor does not seem to significantly increase the CD34+ stem cells and other cell subsets. It is possible that the duration of infusion was too short to mobilise the stem cells. Further studies are warranted to investigate this further. Disclosures:Off Label Use: Plerixafor for stem cell mobilzation from placenta. Shaw:Therakos, a Johnson and Johnson company: Honoraria, Speakers Bureau.

Effect of Plerixafor on Graft Lymphocyte Subsets in NHL Patients Mobilizing Poorly with Chemotherapy Plus G-CSF

Abstract 1929A combination of chemotherapy plus G-CSF (chemomobilization) is commonly used to mobilize CD34+ cells to circulation. Mobilization of CD34+ cells is poor or suboptimal in 20–30 % of patients. Plerixafor, a CXCR4 antagonist, increases the mobilization of CD34+ cells and may also have effect on graft composition subsequently collected. There are no data on lymphocyte subsets in the grafts collected after chemomobilization plus pre-emptively given plerixafor.We have analyzed lymphocyte subsets (CD3, CD4, CD8, NK cells, CD19) in grafts collected on the next morning after plerixafor injection in 13 chemomobilized patients with non-Hodgkin lymphoma. As controls we had the first collections from 13 NHL patients mobilized with chemotherapy plus G-CSF and with yield of 2–6 × 106/kg CD34+ cells with 1–2 aphaereses.The median CD34+ content of the analyzed grafts was 1.45 × 106/kg in the plerixafor group compared to 1.8 × 106/kg in the controls (p=n.s.). The number of T-cell subsets and NK cells were significantly higher in plerixafor mobilized grafts (Table 1). CD19+ B cells were infrequent in both groups.Table 1Lymphocyte subsets of the grafts.Stem cell collection with plerixafor, median (range)Stem cell collection without plerixafor, median (range)Significance pGraft volume (ml)100 (43–190)80 (45–140)0.280Graft sample preservation time (days)299 (31–450)291 (103–397)0.898CD34+ cell content (x 106/ kg) after 7-AAD1.45 (0.40–4.40)1.80 (0.31–4.74)0.858CD3+ cell content (x 106/kg)75.3 (14.6–327.3)21.3 (9.1–159.4)0.004CD4+ cell content (x 106/kg)32.7 (10.6–132.8)12.4 (6.9–51.5)0.002CD8+ cell content (x 106/kg)33.4 (4.2–200.5)8.8 (2.2–125.0)0.006CD19+ cell content (x 106/kg)0 (0–0)0 (0–0)NANK cell content (x 106/kg)5.1 (0.2–30.40)1.5 (0.3–8.0)0.045CD4+/CD8+ cell ratio0.98 (0.34–3.04)1.41 (0.28–5.06)0.2287-AAD, 7-Aminoactinomycin D; NK, natural killer.All except one patient has received high-dose therapy with blood stem cell support. The median CD34+ cell dose was 3.1 × 106/kg in plerixafor treated group and 3.3 × 106/kg in the control group, respectively. Time to neutrophil engraftment was comparable between the groups. There were two patients in the plerixafor group with late platelet engraftment (1 and 6 months).Addition of plerixafor to chemomobilization in poor mobilizers results in increased content of T lymphocytes and NK cells in the graft but do not appear to mobilize B lymphocytes. Whether higher T cell and NK cell content are associated with more rapid immune reconstitution and survival should be evaluated in larger patient series with longer follow-up. Disclosures:Jantunen:Genzyme: Honoraria. Kuittinen:Roche: Consultancy.