Apheresis Yield Research Articles

The CAR T-cell race: The rules of the game.

The management of paediatric patients with refractory acute lymphoblastic leukaemia eligible for the CAR T cell product tisagenlecleucel involves multiple decision points between the process of patient referral to product infusion. How to address the individual patient's circumstances, optimize apheresis yields and, above all, plan the best bridging chemotherapy is clearly detailed in these comprehensive and practical recommendations by Kumar Mishra and colleagues. Commentary on: Mishra etal. Practice guideline: Preparation for CAR T-cell therapy in children and young adults with B-acute lymphoblastic leukaemia. Br J Haematol 2024;204:1687-1696.

G-CSF + plerixafor versus G-CSF alone mobilized hematopoietic stem cells in patients with multiple myeloma and lymphoma: a systematic review and meta-analysis

Aim The combination of granulocyte-colony stimulating factor (G-CSF) and plerixafor is one of the approaches for hematopoietic stem cell mobilization in patients with multiple myeloma (MM), non-Hodgkin’s lymphoma (NHL), and Hodgkin’s lymphoma (HL). This systematic review and meta-analysis aimed to determine the ability of G-CSF + plerixafor to mobilize peripheral blood (PB) CD34+ cells and examine its safety profile. Methods We performed a database search using the terms ‘granulocyte colony stimulating factor’, ‘G-CSF’, ‘AMD3100’, and ‘plerixafor’, published up to May 1, 2023. The methodology is described in further detail in the PROSPERO database (CRD42023425760). Results Twenty-three studies were included in this systematic review and meta-analysis. G-CSF + plerixafor resulted in more patients achieving the predetermined apheresis yield of CD34+ cells than G-CSF alone (OR, 5.33; 95%, 4.34–6.55). It was further discovered that G-CSF + plerixafor could mobilize more CD34+ cells into PB, which was beneficial for the next transplantation in both randomized controlled (MD, 18.30; 95%, 8.74–27.85) and single-arm (MD, 20.67; 95%, 14.34–27.00) trials. Furthermore, G-CSF + plerixafor did not cause more treatment emergent adverse events than G-CSF alone (OR, 1.25; 95%, 0.87–1.80). Conclusions This study suggests that the combination of G-CSF and plerixafor, resulted in more patients with MM, NHL, and HL, achieving the predetermined apheresis yield of CD34+ cells, which is related to the more effective mobilization of CD34+ cells into PB.

Collection efficiency in apheresis

Significant advances in procedural information displayed by current apheresis machines have been made, but analyses of cell collection efficiency (CE) still rely on calculations done by apheresis professionals. Accordingly, understanding CE equations can support the optimization of apheresis techniques and identification of incidents that could impact the procedure’s effectiveness. This report summarizes classical and novel CE analyses applied to apheresis exemplified by an actual case of hematopoietic progenitor cell collection. In addition to the apheresis yield and most common CE1 and CE2 formulas, we present the instantaneous and corrected CE, fold enrichment, collection throughput, collection rate and its variants, average inlet rate, classical and adjusted captured cells, recruitment pool, recruitment factor, recruitment coefficient, blood component loss, predictive apheresis yield, and performance ratio calculations. Moreover, the mathematical relationship between these CE equations is also shown, which can be helpful in many apheresis procedures.

Hematopoietic stem cell mobilization.

ABSTRACTHematopoietic stem cell (HSC) transplantation has been used to treat hematopoietic diseases for over 50 years. HSCs can be isolated from bone marrow (BM), umbilical cord blood, or peripheral blood. Because of lower costs, shorter hospitalization, and faster engraftment, peripheral blood has become the predominant source of HSCs for transplantation. The major factors determining the rate of successful HSC transplantation include the degree of human leukocyte antigen matching between the donor and recipient and the number of HSCs for transplantation. Administration of granulocyte colony-stimulating factor (G-CSF) alone or combined with plerixafor (AMD3100) are clinical used methods to promote HSC mobilization from BM to the peripheral blood for HSC transplantations. However, a significant portion of healthy donors or patients may be poor mobilizers of G-CSF, resulting in an insufficient number of HSCs for the transplantation and necessitating alternative strategies to increase the apheresis yield. The detailed mechanisms underlying G-CSF-mediated HSC mobilization remain to be elucidated. This review summarizes the current research on deciphering the mechanism of HSC mobilization.

P-173: Impact of Daratumumab (DARA) administration during transplant-eligible newly diagnosed Multiple Myeloma (TE NDMM) induction on stem cell (SC) mobilization count and post-transplant engraftment

In the MAX Dara study, Dara-CTd was used sequentially close to the pre- and post-ASCT (D-30 and D + 30), in order to take advantage of the Dara as an in vivo purge. However, dara could interfer in the SC collection and bone marrow engraftment. In this analysis, we examine the impact of the number of Dara doses administered pre-mobilization on CD34 cell count, SC apheresis yield, and post-ASCT engraftment. This is a phase II, open-label single-center clinical trial. The original protocol was Dara-CTd for up to four 28- day induction cycles and Dara-Td for up to four 28 days consolidation cycles. C-1500mg PO per cycle, during cycles 1 to 4, T at 100-200mg PO on days 1 to 28, during cycles 1-8, (d) at 160mg PO per cycle, during cycles 1 - 8 and Dara at 16mg/Kg/dose IV QW during cycles 1 - 2 and QOW in cycles 3 – 8. Because of the COVID pandemic we had to adapted the protocol and moving 5-6 consolidation cycles to be used as induction, increasing the total dose of Dara from 12 to 16 and the number of cycles from 4 to 6 before ASCT. G-CSF was administered alone for SC mobilization and plerixafor added based on day 4 preharvest PB CD34 counts. The target of SC collection was (>2,5×10⁶/kg). PMN and platelet engraftment post-ASCT was defined as the first day with sustained PMN count >1000×10⁶/L and independence from platelet transfusion in the preceding 7 days with a count ≥20×10⁹/L, respectively. From a total of 21 included pts, 19 pts completed mobilization. 12 pts received 12 and 7 pts received 16 induction Dara doses, respectively. The median number (range) of days between the last dose of Dara infusion and SC harvest was 23 (16-63) days. A total of five (26%) pts received plerixafor during mobilization. More pts from Dara 16 doses needed plerixafor comparing with Dara 12 doses (42% vs 16%), but without statistic difference. Pts underwent a median (range) of 1 (1-2) days of apheresis. The median number of CD34+ cells collected in the total group was 3.94×10⁶/kg, and no difference was found between Dara 12 vs 16 doses (3.61×10⁶/kg vs 4.01×10⁶/kg), p=0.27. There was no difference in the number of SC collected considering the response rate after induction > or or 1000 cells/mm³, and a median (range) of 12.0 (9-14) vs 11.0 (8-16) days was required to achieve sustained platelets >20,000 cells/mm³ without transfusion, respectively. In summary, SC mobilization was feasible with Dara-CTd induction. Despite the more doses of Dara use before mobilization increases the need of plerixafor use, the SC number difference was not significant comparing Dara 12 vs 16 doses (p=0.3). The infusion of Dara close to harvest didn't interfere with SC collection. Adding DARA to CTd allowed successful transplantation in pts with TENDMM.

IMPACT OF DARATUMUMAB (DARA) ADMINISTRATION DURING TRANSPLANT- ELIGIBLE NEWLY DIAGNOSED MULTIPLE MYELOMA (TE NDMM) INDUCTION ON STEM CELL (SC) MOBILIZATION COUNT AND POST-TRANSPLANT ENGRAFTMENT

The combination of an anti-CD38 monoclonal antibody, Dara, to the main induction protocols (VRd, VTd,VCd) significantly improved the response rate of TE NDMM before transplantation. However, there is a concern regardingthe possible interference in the SC collection and bone marrow engraftment, since SC, to some degree, express CD38on their surface. In the MAX Dara study, Dara-CTd protocol was used sequentially close to the pre- and post-autologousstem cell transplantation-(ASCT) (D-30 and D + 30), in order to take advantage of the molecule's action as an in vivopurge. In this analysis, we examine the impact of the number of Dara doses administered pre-mobilization on CD34 cellcount, SC apheresis yield, and post-ASCT engraftment. This is a phase II, open-label single-center clinical trial. The original protocol was Dara-CTd for up to four 28-day induction cycles and Dara-Td for up to four 28 days consolidation cycles. C-1500 mg oral (PO) per cycle, duringcycles 1 to 4, T at 100-200 mg PO on days 1 to 28, during cycles 1-8, (d) at 160 mg PO per cycle, during cycles 1 - 8 andDara at 16 mg/kg/dose intravenous (IV) on days 1,8,15 and 22 during cycles 1 - 2 and every other week in cycles 3 – 8. Because of the Covid pandemic we had to adapted the protocol and moving 5-6 consolidation cycles to be used asinduction, increasing the total dose of Dara from 12 to 16 and the number of cycles from 4 to 6 before ASCT. Granulocytecolony-stimulating factor (G-CSF) was administered alone for SC mobilization and plerixafor added based on day 4 preharvestperipheral blood CD34 counts. The target of SC collection was to enable the performance of one ASCT (>2,5 x 106/kg). PMN and platelet engraftment post-ASCT was defined as the first day with sustained PMN count >1000 x 106/L andindependence from platelet transfusion in the preceding 7 days with a count >20 x 109/L, respectively From a total of 21 pts that were included, 19 pts completed mobilization. 12 pts received 12and 7 pts received 16 induction Dara doses, respectively. The median number (range) of daysbetween the last dose of Dara infusion and SC harvest was 23 (16-63) days. A total of five (26%) ptsreceived plerixafor during mobilization. More pts from Dara 16 doses needed plerixafor comparingwith Dara 12 doses (42% vs 16%), but without difference between the groups. Pts underwent amedian (range) of 1 (1-2) days of apheresis. The median number of CD34+ cells collected in the totalgroup was 3.94×106/kg, and no difference was found between Dara 12 vs 16 doses (3.61×106/kg vs4.01x106/kg), p = 0.27. There was no difference in the number of SC collected considering theresponse rate after induction > or < VGPR, and the last day of Dara use > or < 30 days, before SCharvesting. Hematopoietic reconstitution rates were similar for Dara 12 vs 16 doses, a median(range) of 11.0 (9-13) vs 11.0 (11-14) days was required to achieve sustained ANC > 1000 cells/mm3, and a median (range) of 12.0 (9-14) vs 11.0 (8-16) days was required to achieve sustained platelets> 20,000 cells/mm3 without transfusion, respectively. SC mobilization was feasible with Dara-CTd induction. Despite the more doses of Dara usebefore mobilization increases the need of plerixafor use, the SC number difference was not significant comparing Dara 12vs 16 doses (p = 0.3). The infusion of Dara close to harvest did not interfere with SC collection. Adding DARA to CTdallowed successful transplantation in pts with TE NDMM.

Comparison of CD34+ cell mobilization, blood graft cellular composition, and post-transplant outcome in myeloma patients mobilized with filgrastim or pegfilgrastim added to low-dose cyclophosphamide: A prospective multicenter study.

Scarce data exist on the impact of granulocyte-colony stimulating factor (G-CSF) type on the mobilizing capacity of CD34+ cells, graft cellular composition, and outcome in myeloma (MM) patients. In this prospective multicenter study, 70 patients with MM received filgrastim (FIL) and 20 patients received pegfilgrastim (PEG) as a G-CSF after low-dose cyclophosphamide. Flow cytometry was used to analyze the mobilization of CD34+ cells and cellular composition of blood grafts, hematologic recovery, and survival after auto-SCT according to the G-CSF choice. The CD34+ cell yield of the first apheresis was higher in the FIL group (5.3 vs. 4.2 × 106 /kg, p=.025). The better mobilizing capacity was observed in the FIL group especially after bortezomib-based induction based on the higher first apheresis yield of CD34+ cells (7.5 vs. 4.4 × 106 /kg, p=.001). The median CD19+ cell count (1.0 vs. 0.4 × 106 /kg, p=.010) and the number of CD3+ T lymphocytes (43.1 vs. 31.8 × 106 /kg, p=.122) in the infused graft were higher in the patients mobilized with FIL. Both early (day +15) (56 vs. 108 × 109 /L, p=.002) and later platelet recovery at 6 months (191 vs. 226 × 109 /L, p=.026) were faster in the PEG group. G-CSF type seems to impact on the mobilization capacity and cellular composition of infused graft and also platelet recovery post-transplant. A randomized study might be warranted to verify the effects of G-CSF choice in the mobilization field.

Autologous Hematopoietic Progenitor Cells Mobilization with Combination of Pegfilgrastim and Plerixafor: Efficacy and Cost Assessment

Introduction: Filgrastim (FIL), administered as 4 or more daily multi-vial subcutaneous injections is the most commonly utilized growth factor for mobilization of autologous hematopoietic progenitor cells (auto-HPC) for transplantation. Plerixafor, a CXCR4 inhibitor, potentiates the effect of FIL by increasing the pool of circulating CD34+ cells and apheresis yield. Pegfilgrastim (PEG) is a long acting modification of FIL. Prior experience indicates that single fixed dose PEG can be utilized for auto-HPC mobilization with at least similar performance compared to daily, weight-based dose FIL, but cost is a concern.Methods: We adopted a standardized mobilization protocol consisting of PEG 6 mg on day 1, plerixafor 240 mcg/kg on day 3 and collection of auto-HPC by apheresis on day 4. When CD34+ collection target (3 x 106 CD34+/kg for patients collecting for 1 transplant and 6 x 106 CD34+/kg for patients collecting for 2 transplants) was not met on the first day of collection, evening plerixafor administration followed by next-day collection was repeated until target met or a maximum of 3 collections. Auto-HPCs were collected by apheresis with processing of approximately 3 blood volumes utilizing Cobe® Spectra or AmicusTM machine. Mobilization failure was defined as a collection < 2 x 106 CD34+/kg, considered the minimum cell dose for one transplant procedure. We prospectively collected information on mobilization outcomes for 164 consecutive auto-HPC mobilizations. We compared the estimated cost of mobilization drugs with PEG vs. simulated cost with FIL or tbo-filgrastim (TBO) at dose of 10 mcg/kg/day administered for 4 days prior to first collection and daily until collection completion, with this regimen assumed to be of similar efficacy than PEG. Drug costs were estimated using average sales price (ASP): PEG $4,191.34/ 6mg, FIL $1.009/ 1mcg, TBO $0.665/ 1mcg, and plerixafor $312.10/ 1mg. Actual body weight was used for estimation of FIL and TBO dose.Results: Among the 164 consecutive patients, 11 had the diagnosis of Hodgkin lymphoma, 20 non-Hodgkin lymphoma and 133 multiple myeloma or another plasma cell dyscrasia. Median age of patients was 60 years (range 21-73) and 92 (56%) were men. Median weight of patients was 84kg (range 51-175). Among the patients with a plasma cell dyscrasia, 87 (65%) had received prior lenalidomide, an agent known to impair HPC mobilization. Overall 4 patients (2.4%) had mobilization failure. One hundred and forty-two (87%) met the pre-established target while 18 (11%) collected enough CD34+ cells to proceed to transplant but fewer cells than pre-established target. The median CD34+/mm3 in peripheral blood on the first day of collection was 71 (range 2-481). The median collection yield on the first day was 6.06 x 106 CD34+/kg (range 0.34-39.60) and median total collection yield was 4.52 x 106 CD34+/kg (range 0.81-18.60) for patients with target of 3 x 106 CD34+/kg and 7.97 x 106 CD34+/kg (range 0.34-39.60) for patients with target of 6 x 106 CD34+/kg. Overall 77 (47%) patients had 1 day, 65 (40%) had 2 days and 22 (13%) had 3 days of collection. For patients requiring multiple days of collection, there was no substantial day-by-day decline in apheresis yield. In fact, median yield on days 2 and 3 were 106% and 97% of yield from day 1. There were no severe adverse toxicities from the mobilization regimen. All patients who have undergone transplantation successfully engrafted neutrophils and platelets. Average estimated cost of mobilization drugs with PEG + plerixafor was $14,588, comparable to estimated cost for FIL + plerixafor ($15,399) and TBO + plerixafor ($13,693). Since FIL and TBO are dosed daily and dose is weight-based, the cost comparison with PEG is greatly influenced by patient weight and number of apheresis sessions required (Figure).Conclusion: PEG plus plerixafor is a convenient, safe, effective and predictable regimen for auto-HPC mobilization. In this setting, PEG cost is comparable to FIL or TBO, being potentially cost-saving in heavier patient. [Display omitted] DisclosuresSaad:Actinium: Consultancy; Spectrum: Honoraria.

Timing of Daratumumab Administered Pre-Mobilization in Multiple Myeloma Impacts Pre-Harvest Peripheral Blood CD34+ Cell Counts and Plerixafor Use

Background: Daratumumab (DARA) is a monoclonal antibody which targets CD38 on plasma cells and B cell progenitors. DARA has been effectively combined with other therapies in newly diagnosed and relapsed/refractory multiple myeloma (RRMM), while DARA-based induction regimens in transplant-eligible patients (pts) are increasingly being used in clinical practice. Given that hematopoietic stem cells also express CD38, DARA may potentially affect stem cell mobilization and hematopoietic reconstitution following autologous stem cell transplant (ASCT). Although no clinically significant impact of DARA on stem cell mobilization or hematopoietic recovery was described in large phase 3 trials of triplet induction regimens +/- DARA in newly diagnosed MM, stem cell yields were lower and plerixafor more commonly used in the DARA-containing arms [Moreau et al, Lancet 2019; Voorhees et al, Blood 2020]. Significantly longer time to neutrophil (PMN) engraftment was also reported in pts receiving DARA-based induction who underwent upfront ASCT [Al Saleh et al, Am J Hematol 2020]. In this study, we examine the impact of timing of DARA administration pre-mobilization on day 4 pre-harvest peripheral blood CD34 cell count, stem cell apheresis yield, and post-ASCT engraftment. Methods: Between 1/1/2016 and 12/31/2019, newly diagnosed and RRMM pts receiving DARA-based induction regimens with ≥1 dose of DARA administered within 1 month prior to stem cell mobilization were identified retrospectively and compared to matched controls receiving similar induction regimens without DARA. Granulocyte colony-stimulating factor (G-CSF) was administered per institutional standards and plerixafor added based on day 4 pre-harvest peripheral blood CD34 counts. PMN and platelet engraftment post-ASCT was defined as the first of 3 consecutive days with sustained PMN count &amp;gt;500 x 106/L and independence from platelet transfusion in the preceding 7 days with a count &amp;gt;20 x 109/L, respectively. Pre-harvest peripheral blood CD34 counts and stem cell apheresis yields were obtained from the Cellular Therapy Laboratory at NewYork-Presbyterian Hospital. The study was approved by the Weill Cornell Medicine IRB. Results: We identified 16 pts who received DARA-based induction with ≥1 dose of DARA administered within 1 month of apheresis (DARA group) and 16 non-DARA-containing regimen-matched controls (non-DARA group). Demographics of the DARA and non-DARA groups were well matched (Table 1). DARA pts received their last dose of DARA a mean of 17.3 days prior to the first day of apheresis, with 8 pts receiving their last dose within 2 weeks and the remaining 8 pts between 2 weeks and 1 month prior. Overall, mobilization outcomes were inferior in the DARA group (Table 2). DARA pts had significantly lower day 4 pre-harvest peripheral blood CD34 counts compared to non-DARA pts (17.2 vs 35.4 cells/µL; P=0.0146). Institutional algorithm required plerixafor to be given for day 4 CD34 count ≤40 cells/µL. Fifteen of the 16 DARA pts received plerixafor vs. 11 non-DARA pts (P=0.07). Additionally, DARA pts required significantly more apheresis days (2.4 vs 1.6 days; P=0.0279). Differences in stem cell yield were not significant (8 vs 10 x106cells/kg; P=0.1391). Hematopoietic recovery post-ASCT was not affected by DARA administered in the month preceding mobilization. Conclusions: In summary, we report lower day 4 pre-harvest peripheral blood CD34 count, increased requirement for plerixafor, and longer apheresis duration in newly diagnosed and RRMM pts receiving DARA within 1 month ofstem cell mobilization. These limitations are largely overcome by plerixafor usage which, combined with G-CSF, resulted in successful stem cell collection in all patients. Limitations in our study include small sample sizes, retrospective control selection, and fewer pts in the DARA group achieving ≥VGPR prior to mobilization. Nevertheless, our findings are consistent with inferior mobilization outcomes reported in the DARA-containing arms of phase 3 trials of triplet induction +/- DARA and highlight the nearly universal requirement for plerixafor usage when DARA is administered within a month prior to apheresis. Prospective study of day 4 pre-harvest peripheral blood CD34 counts and other predictors of stem cell yield should be incorporated into future clinical trials of CD38 monoclonal antibody-based induction regimens for transplant-eligible MM pts. Disclosures Rossi: Janssen: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees. Niesvizky:GSK: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Takeda: Consultancy, Honoraria. Rosenbaum:Amgen: Research Funding; GlaxoSmithKline: Research Funding; Akcea: Honoraria; Celgene: Honoraria; Janssen: Research Funding.

Evaluation of the Sysmex XN automated hematopoietic progenitor cell enumeration for timing of peripheral blood stem cell harvest

BackgroundEnumeration of stem cells is essential in the management of peripheral blood stem cell (PBSC) harvest. An alternative to the gold standard flow cytometric CD34+ stem cell count is the fully automated hematopoietic stem cell (HPC) count on the Sysmex XN hematology analyzer. Materials and methodsEighty-nine patients and healthy stem cell donors who underwent PBSC harvest were included in the study. Stem cells were enumerated in pre-harvest peripheral blood and the apheresis yield by both flow cytometric CD34+ stem cell enumeration and by the Sysmex XN HPC count. ResultsThe Sysmex HPC concentration overestimated the CD34+ stem cell concentration by a ratio of 1.3 in average. The agreement between the two methods was poor at concentration <40 stem cells/μL (Bias: 45 %, 95 % limits of agreement: -71 - 160 %). CD34+ stem cell concentration and HPC concentration correlated well in pre-harvest peripheral blood (R=0.73, slope=0.96). We established a positive cut off >43.5 HPC/μL, where PBSC harvest can be initiated. And a negative cut off <16.5 HPC/μL, where harvest should be postponed or other mobilizing regimens or bone marrow harvest should be considered. 33 % of measurements were in between the negative and positive cut-off and would require a supplementary CD34+ cell count. ConclusionAlthough Sysmex HPC count correlates well with CD34+ cell count in peripheral blood, the agreement between the two methods is poor, especially at low concentrations, namely in the clinical decision range. Sysmex HPC count as a surrogate for CD34+ cell count should, therefore, be used with caution.

The Impact of Different Mobilization Strategies in the Setting of Multiple Myeloma

INTRODUCTION Multiple myeloma (MM) is considered an incurable disease. Despite the introduction of novel agents allowed deeper response, high-dose chemotherapy and autologous stem cell transplantation (ASCT) remain the standard of care for patients (pts) in good clinical conditions. The most used strategies to mobilize stem cells from bone marrow (BM) into peripheral blood are high-dose cyclophosphamide (HD-CTX) plus G-CSF and G-CSF plus plerixafor (G-CSF+P). The goal of this retrospective study is to investigate whether the two different mobilization strategies have an impact on the clearance of monoclonal PCs in the apheresis products and on pts' outcome. PATIENTS AND METHODS We analyzed 62 pts (median age 61, range 41-75, 37 males and 25 women) diagnosed with MM and treated with ASCT between Mar 2014 and Mar 2018 at our Hematology Division (Pisa, Italy). All pts received induction therapy with at least 4 cycles of bortezomib, thalidomide and dexamethasone (VTD). 9/62 pts obtained a less than partial response (PR) and received lenalidomide-based regimens. After induction, 8 (12,9%) pts achieved complete remission (CR), 26 (41,9%) were in PR, 28 (45,2%) obtained a very good partial response (VGPR). 43/62 fit pts received HD-CTX (2-3 g/sqm) on day 1 followed by G-CSF (30 MU/day) started on day 4 until day 7, increased to 60 MU/day from day 8 until the end of apheresis. In 19/62 pts, after 4 days of G-CSF (60 MU/day) administration and not sufficient mobilization, we added plerixafor (0,24 mg/kgbw) for up to 4 consecutive days. In 43/62 pts we collected apheresis samples (10μl) analyzed through flow citometry to enumerate clonal residual PCs. The panel used to asses clonality included: CD138 Per-Cp, CD38 APC, CD19 PE-Cy7, CD45 APC-Cy7, cytoplasmic immunoglobulin K chain and L chain. RESULTS At the end of the peripheral blood stem cell (PBSC) collection, pts treated with HD-CTX presented a higher CD34+ absolute count (p=0.0489) and achieved the threshold of 5x106 CD34+ cells/kgbw in a significantly (p=0.006) higher percentage. We found a nearly significant (p=0.0517) lower count of CD34+ PBSCs in pts who received lenalidomide-based regimens before the mobilization. Performing flow citometry on apheresis samples, we observed that the number of the harvested clonal PCs showed a significant correlation (p=0.0115) with the occurrence of post-ASCT relapse. ROC curve analysis investigating the predictive effect of the number of pathological PCs on disease relapse showed an area under the curve of 0,6978 (95% CI 0.5392-0.8564; p=0.0267). Neither BM residual PCs detectable on BM biopsies performed before apheresis (r=-0.1323; p=0.609) nor the type of mobilization scheme (p=0.707) had an impact on the proportion of clonal PCs in the graft. Additionally, we did not observe any statistically significant difference in progression free- (PFS) (p=0.8276) and overall survival (OS) (p=0.2475) between the HD-CTX and G-CSF+P groups. DISCUSSION PBSC mobilization has a succession rate &gt; 85%. Despite the use of HD-CTX to increase PBSC yields and decrease tumor burden, there is not clear evidence of a superior mobilization strategy. Additionally, HD-CTX has a not negligible toxicity and approximately 10% of the pts require hospitalization. Conversely, G-CSF+P is a safe and effective approach also in poor mobilizers. In our study, we observed a significative difference in the apheresis yields (p=0.0489) and in the percentage of pts who achieved the threshold of 5x106 CD34+ cells/kgbw (p=0.006) in favor of HD-CTX. Additionally, the detection of harvested residual clonal PCs could be a promising strategy to recognise pts more likely to relapse after ASCT. Nonetheless, we failed to demonstrate a superior effect of HD-CTX in the clearance of harvested clonal PCs, in agreement with the absence of a different pts' outcome amongst the two mobilization strategies. In conclusion, the choice between the two regimens is challenging and requires careful consideration of multiple factors. Overall, young fit pts, especially in the high-risk setting, should be treated with all appropriate modalities including chemiomobilization followed by double-ASCT. Conversely, in pts candidate to a single-ASCT it is reasonable to use G-CSF+P, since HD-CTX does not improve PFS and OS and add toxicity. The absence of an in-vivo purging effect on apheresis products of chemiomobilization further strengthens a chemotherapy-free mobilization. Disclosures Galimberti: Roche: Speakers Bureau; Celgene: Speakers Bureau; Novartis: Speakers Bureau.

Mgta-145 in Combination with Plerixafor Mobilizes Large Numbers of Hematopoietic Stem Cells That Lead to Rapid Engraftment Following Autologous Transplantation in Nonhuman Primates

The majority of bone marrow transplants (BMT) utilize granulocyte-colony stimulating factor (G-CSF) mobilized peripheral blood (mPB) as the source of hematopoietic stem cells (HSCs). However, CD34+ harvest with G-CSF is variable and frequently unpredictable, often requires multiple apheresis sessions and is associated with significant side effects. Identification of a mobilizing regimen that consistently produces high numbers of engraftable CD34+ cells without the need for G-CSF would be ideal. We previously reported that MGTA-145, a CXCR2 agonist, when combined with the CXCR4 inhibitor, plerixafor, rapidly mobilizes CD34+ cells (Blood 2017 130:1920). In the current study, we evaluated the ability of MGTA-145 plus plerixafor to mobilize and effectively engraft HSCs in a pre-clinical nonhuman primate (NHP) stem cell transplantation animal model. Rhesus macaques were mobilized with a single dose of MGTA-145, plerixafor or MGTA-145 plus plerixafor versus a multi-dose regimen of G-CSF. Detailed immune profiling was performed at 0 through 24 hours post treatment. Within 4 hours of dosing, MGTA-145 plus plerixafor resulted in a 16-fold increase in the number of CD34+CD90+CD45RA- HSCs in the periphery (p=0.0003, n=11), which were previously shown to predict successful transplant as evidenced by rapid neutrophil and platelet recovery in an autologous NHP transplant model (Sci Trans Med 2017 9:1145). Next, NHPs mobilized with MGTA-145 plus plerixafor were leukapheresed and CD34+ cells enriched by positive selection. These cells were genetically modified and transplanted back into the same NHP conditioned with 1080 cGy (4 doses over 48 hours). A representative apheresis yield was 2.3 × 106 CD34+ and 0.9 × 106 HSCs per kg, and the final dose of gene-marked CD34+ and HSCs for transplant following 48 hours in culture was 1.7 × 106 and 0.8 × 106 per kg, respectively. GFP marking in vivo was consistent with the marking on the primitive HSCs prior to transplant. Neutrophil and platelet engraftment occurred at day 10 and 15 post-transplant, respectively (Figure 1). The study is ongoing, and additional follow-up data on all available animals will be presented. Co-administration of MGTA-145 plus plerixafor leads to both rapid and efficacious mobilization of CD34+ cells in the pre-clinical NHP large animal model. We found that MGTA-145 plus plerixafor mobilized grafts contain large numbers of CD34+CD90+CD45RA- HSCs, which are capable of long-term multilineage reconstitution, and preliminary results from autologous transplantation studies in NHPs demonstrate that MGTA-145 plus plerixafor mobilized HSCs lead to rapid neutrophil and platelet recovery. This study demonstrates, for the first time, that CD34+ cells mobilized with a novel regimen of MGTA-145 plus plerixafor can be collected via leukapheresis, subsequently gene modified and transplanted into NHPs, resulting in rapid engraftment.

Flipping the Switch: Initial Results of Genetic Targeting of the Fetal to Adult Globin Switch in Sickle Cell Patients

▪Autologous gene therapy (GT) for beta-hemoglobinopathies has demonstrated encouraging early safety and efficacy using addition of a sickling-resistant globin gene to stem cells. Another therapeutic strategy for sickle cell disease (SCD) is erythroid-specific inactivation of BCL11A, which is a validated repressor of gamma globin expression (Sankaran et al. Science 2011). This approach has the distinct advantage of simultaneously inducing fetal hemoglobin (HbF) while coordinately decreasing sickle hemoglobin (HbS). Since hemoglobin (Hb) polymerization in sickle red cells is highly dependent on the intracellular concentration of HbS and is strongly inhibited by HbF, effective BCL11A repression should prevent the sickling phenotype within red cells. We have shown that erythroid-specific expression of microRNA-adapted shRNAs (shRNAmiR) targeting BCL11A effectively induces HbF in human erythroid cells derived from transduced HSCs, largely attenuating the hematologic effects of SCD in a murine model while avoiding negative effects in HSCs and B lymphocytes (Brendel et al. JCI 2016). Here we report the initial results of a pilot clinical study utilizing a shRNAmiR lentiviral vector (LVV) targeting BCL11A for autologous GT in SCD patients.Transduction of hematopoietic cells with GMP lentiviral vector (BCH_BB-LCRshRNA(miR)) expressing the shRNAmiR for BCL11A in an erythroid-specific fashion showed no toxicity in engraftment and genotoxicity assays, efficient transduction rates of 80-95% of CD34+-derived erythroid colony forming cells from healthy donors and SCD patients, and >95% of transduced erythroid colonies demonstrating HbF levels of 50-95% of total Hb. Transduction at clinical scale with plerixafor mobilized CD34+ cells from three SCD donors yielded vector copies of 3.7 - 5.2/cell.Patients with severe SCD were screened for eligibility according to an IND enabled, IRB-approved investigator-initiated protocol. The first cohort included patients ≥ 18 years old. After at least 3 months of protocol-required transfusions, autologous CD34+ cells were collected by plerixafor mobilization and apheresis, and then transduced under GMP conditions with the BCH_BB-LCRshRNA(miR) vector. As of July 28, 2018, 3 patients representing the adult cohort had undergone a total of 3 (n=2) or 4 (n=1) days of mobilization. Mean single-day apheresis yields were 3.2 (range 1.5 - 6.8) x 106 CD34+ cells/kg. No Grade 3 or 4 AEs were attributed to mobilization and collection, although one subject developed an incidentally-discovered line-associated atrial clot and pulmonary embolism. Transduced cell products for these 3 patients have cell doses of 3.3 - 6.7 x 106 CD34+ cells/kg, VCN of 3.3 - 5.1 copies per cell and >95% vector-positive CD34+-derived colonies. One subject (BCL002), who had been regularly transfused for 17 years, has undergone infusion of gene-modified cells after myeloablative busulfan conditioning and achieved neutrophil engraftment after 22 days. Post-infusion follow-up is 78 days. At the time of the last analysis 76 days after GT and 64 days after last RBC transfusion (Table 1) subject BCL002 had a sustained Hb of >10 g/dL and, compared to pre-GT, there was a notable absence of irreversibly sickled cells on peripheral smear and a persistently low absolute reticulocyte count consistent with markedly reduced hemolysis. Hb electrophoresis showed 23.3% HbF, 51.8% HbS and 22.3% HbA (from residual transfused cells) with a HbF/(HbF+HbS) ratio of 29.7%. At day 76, the number of F cells had risen to 59.7% with 12pg HbF/F cell. In flow-sorted immature erythroid cells γ-globin mRNA was >80% of total β-like globins in the graft-derived population and BCL11A protein was reduced by ~90%. Adverse events observed from the start of conditioning until latest follow-up were consistent with myeloablative conditioning, and there have been no product-related adverse events and no SCD-related complications.These early results show: (1) feasibility of enrollment, cell procurement, and GMP manufacturing of gene modified CD34+ cells in 3 adult SCD patients; (2) the first proof of principle demonstrating shRNAmiR-based gene knockdown in humans, and (3) successful rapid induction of HbF in the first patient infused, with marked attenuation of hemolysis in the early phase of autologous reconstitution. Based on the trajectory of increasing HbF/(HbF+HbS), near full suppression of the SCD phenotype is expected. [Display omitted] DisclosuresEsrick:Bluebird Bio: Honoraria. Negre:bluebird bio: Other: Spouse employed by bluebird Bio. Dansereau:Bluebird Bio: Consultancy. Braunewell:Bluebird Bio: Employment, Equity Ownership. Christiansen:Bluebird Bio: Employment, Equity Ownership, Other: Salary. Nikiforow:Kite Pharma: Consultancy. Achebe:Luitpold Pharmaceutical: Consultancy; AMAG Pharmaceuticals, Inc.: Membership on an entity's Board of Directors or advisory committees; Syros pharmaceuticals: Consultancy. Negre:Bluebird Bio: Employment, Equity Ownership, Other: Salary. Heeney:Sancilio Pharmaceuticals: Consultancy, Research Funding; Ironwood: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees; Vertex/Crisper: Other: Data Monitoring Committee; Pfizer: Research Funding; Astra Zeneca: Consultancy, Research Funding. Williams:Bluebird Bio: Research Funding.

Plerixafor in poor mobilizers with non-Hodgkin\u2019s lymphoma: a multi-center time-motion analysis

High-dose chemotherapy alongside peripheral blood stem cell (PBSC) infusion has become the standard of care in different hematologic malignancies. The goal of PBSC mobilization is to allow collection of sufficient CD34+ cells to proceed to transplantation. The current mobilization regimen with granulocyte colony-stimulating factor (G-CSF), alone or in combination with chemotherapy, still fails in 10–25% of patients. Plerixafor is able to rescue most of these patients from mobilization failure. In this study, we investigated the impact of plerixafor on the cost and time spent on apheresis in patients who were considered poor mobilizers, with <20 × 106/µl peripheral CD34+ cells after mobilization but prior to apheresis. Patient hospital records from ten centers in three European countries were reviewed and compared during two time periods, namely prior and after plerixafor introduction to the market. During the plerixafor period, patients spent less time on apheresis (350 vs. 461 min). Poor mobilizers given plerixafor collected more CD34+ cells during the first apheresis session, leading to a decrease in the average number of apheresis sessions needed. The total apheresis yield was unaffected. This analysis shows that the use of plerixafor lessens the time–effort associated with the management of poor mobilizers and reduces apheresis costs.

UK consensus statement on the use of plerixafor to facilitate autologous peripheral blood stem cell collection to support high-dose chemoradiotherapy for patients with malignancy.

Plerixafor is a CXC chemokine receptor (CXCR4) antagonist that mobilizes stem cells in the peripheral blood. It is indicated (in combination with granulocyte-colony stimulating factor [G-CSF]) to enhance the harvest of adequate quantities of cluster differentiation (CD) 34+ cells for autologous transplantation in patients with lymphoma or multiple myeloma whose cells mobilize poorly. Strategies for use include delayed re-mobilization after a failed mobilization attempt with G-CSF, and rescue or pre-emptive mobilization in patients in whom mobilization with G-CSF is likely to fail. Pre-emptive use has the advantage that it avoids the need to re-schedule the transplant procedure, with its attendant inconvenience, quality-of-life issues for the patient and cost of additional admissions to the transplant unit. UK experience from 2 major centers suggests that pre-emptive plerixafor is associated with an incremental drug cost of less than £2000 when averaged over all patients undergoing peripheral blood stem cell (PBSC) transplant. A CD34+ cell count of <15 µl-1 at the time of recovery after chemomobilization or after four days of G-CSF treatment, or an apheresis yield of <1 × 106 CD34+ cells/kg on the first day of apheresis, could be used to predict the need for pre-emptive plerixafor.

Successful peripheral blood stem cell mobilization with a cost-efficient single fixed-dose plerixafor schedule in poor mobilizers

Plerixafor, although costly, is added to mobilizing chemotherapy and G-CSF to overcome poor stem cell mobilization. We demonstrate that it can be safely administered mostly once as a single dose in preemptive and rescue settings, leading to apheresis yields of >2 and >4×106 CD34 + cells/kg body weight (bw) in 83% and 48%, respectively. Of note, 35/46 (76%) patients showed a substantial benefit with increased peripheral blood (PB) CD34 + cells prior to apheresis (8.84 vs. 1.72/μl, p < .001), and 5-fold increased CD34 + cells collected per single apheresis (2.25 vs. 0.43 × 106 CD34+/kg bw, respectively, p < .001). Patients profiting most (76%) vs. less (24%) had >5 vs. <5/μl PB CD34 + cells before plerixafor application, respectively, thus careful patient selection in the latter group is advised. To the best of our knowledge, this is the first report demonstrating that favorable apheresis results can be obtained using this cost-efficient, single fixed-dose plerixafor schedule.

Abstract # 1810 Exercise induces a differential mobilisation of haematopoietic stem cell subsets into peripheral blood which is partly influenced by donor age.

Exercise-induced leukocyte mobilisation is well defined, but few studies have examined their precursors – haematopoietic stem cells (HSCs). Seventeen males (33 ± 13 years, BMI 24 ± 3 kg·m2 and VO2max 60 ± 5 ml·kg·min) ran for 60 min at 80% VO2max. Blood was collected at rest, during the final minute of exercise, then 15, 60 and 120 min later. HSC populations were identified using flow cytometry: HSCs (CD34+CD45dim); Common Lymphoid Progenitor cells (CLP, CD34+CD45dimCD38-CD7+); Common Myeloid Progenitor cells (CMP, CD34+CD45dimCD38+CD123+CD45RA-); Megakaryocyte/Erythroid Progenitor cells (MEP, CD34+CD45dimCD38+CD123-CD45RA-); and Granulocyte/Macrophage Progenitor cells (GMP, CD34+CD45dimCD38+CD123+CD45RA+). HSCs increased by 100% during exercise, returning to baseline within 15 min, and fell 10% below baseline 60–120 min post-exercise (p η 2 = 0.44). CLP, CMP and GMPs were un-changed during or following exercise, but CMPs and GMPs fell 30–40% below baseline 1–2 h later (p’s η 2 = 0.37). HSC mobilisation was higher (+80%) in younger men (n = 10, 23 ± 3 years) compared to older men (n = 7, 48 ± 5 years; interaction p η 2 = 0.15). Controlling statistically for absolute heart rate during exercise attenuated the age-effect (p > 0.05; η 2 = 0.14), suggesting the smaller HSC mobilisation in older men was partly due to lower cardiac output and concomitant haemodynamic/shear forces. Exercise-induced HSC mobilisation could increase apheresis yields for transplant, but compared to younger donors, the elderly may require a more prolonged stimulus.

Factors affecting the CD34+ cell yields from the second donations of healthy donors: The steady-state lymphocyte count is a good predictive factor

BackgroundA second allogeneic hematopoietic stem-cell transplantation and donor lymphocyte infusion using cells from the same donor is a therapeutic option in the case of stem-cell graft failure or disease relapse, but little is known about the factors associated with the CD34+ cell yields from second donations. MethodsOne-hundred healthy donors who underwent a second mobilization treatment and peripheral blood stem-cell (PBSC) collection were studied. For both mobilization processes, 5 µg of granulocyte colony-stimulating factor per kg per day was administered. The blood counts of the donors were monitored during the processes. ResultsThe second donations from the same donors provided lower apheresis yields than did the initial collections. The number of CD34+ cells collected from normal donors after a second cycle of PBSC mobilization was associated with their steady-state lymphocyte counts and the intertransplantation interval. Female sex negatively affected the CD34+ cell yields. The cutoff value for the steady-state absolute lymphocyte count was 2.055 × 109/L. ConclusionTo harvest greater numbers of CD34+ cells from second collections, male donors and those with intervals of longer than 9 months between donations should be selected. The lymphocyte counts prior to the first donations may predict the content of CD34+ cells in the allografts prepared using the second donations.

A Randomized Trial of Tbo-Filgrastim Versus Filgrastim for Autologous Stem Cell Mobilization in Patients with Multiple Myeloma or Non-Hodgkin Lymphoma

Background: Tbo-filgrastim, biosimilar to filgrastim, was approved by the FDA in 2012 as a new drug due to the lack of a biosimilar approval pathway at time of submission. Like filgrastim, tbo-filgrastim is currently indicated for the treatment of neutropenia following chemotherapy; however, filgrastim is also indicated for mobilization of hematopoietic progenitor cells for autologous stem cell transplantation (ASCT) while tbo-filgrastim is not. In Europe, tbo-filgrastim carries all the indications that filgrastim does, however, no prospective studies have been completed comparing tbo-filgrastim and filgrastim for ASCT mobilization. Therefore, we conducted a single-institution randomized phase 2 trial.Objectives: 1) To compare peripheral blood (PB) CD34+ counts, CD34+ apheresis yield, toxicity, and post-ASCT engraftment in patients mobilized with tbo-filgrastim versus filgrastim.Methods: Participants were at least 18-years-old and had multiple myeloma (MM) or non-Hodgkin's Lymphoma (NHL). Those with impaired hematologic function and those who had undergone a previous ASCT mobilization were excluded. Participants were randomized (1:1) to tbo-filgrastim or filgrastim. Tbo-filgrastim/filgrastim (10mcg/kg) was administered daily for 5 days. On the evening of Day 4, plerixafor (0.24 mg/kg) was administered; apheresis (20L) was performed on Day 5. If a participant failed to achieve the target collection goal (5.0x106 cells/kg) on Day 5, he/she continued to receive daily tbo-filgrastim/filgrastim, plerixafor, and apheresis for a maximum of 3 additional days. Participants who subsequently underwent ASCT were followed for platelet and neutrophil engraftment.Statistics: PB CD34+ counts and CD34+ apheresis yields were compared using Mann-Whitney U, engraftment using log-rank.Results: At the time of abstract submission, corresponding with interim analysis 1, 51 participants were enrolled and 49 were evaluable for analysis; 24 received tbo-filgrastim, 25 filgrastim. The median age was 60 years (range 40-77); 63% (31) were male; 86% (42) had MM, 14% (7) NHL. Both treatment arms were similar in demographics and baseline blood counts.Post-mobilization PB CD34+ counts were similar between both arms. The median PB CD34+ count on day 4 (pre-plerixafor) was 20/mcL for tbo-filgrastim and 22/mcL for filgrastim (p=0.647); on Day 5 pre-apheresis it was for 94/mcL for tbo-filgrastim and 92/mcL for filgrastim (p=0.726). CD34+ apheresis yield was also similar; the median Day 5 CD34+/kg apheresis yield was 10.9x106 for tbo-filgrastim and 12.0x106 for filgrastim (p=0.889).Seventy-five percent of the tbo-filgrastim arm reached the collection goal after one day of apheresis, 76% of the filgrastim arm did (p=0.935). Ninety-six percent of patients on the tbo-filgrastim arm reached the goal in 4 or less days of apheresis, 92% of the filgrastim arm did (p=0.576). All patients treated collected > 2.0x106 cells/kg, the minimum required for ASCT, following < 2 days of apheresis. Both treatment arms had similar toxicity.Thirty-nine patients have subsequently undergone ASCT and evaluable for engraftment, 18 on the tbo-filgrastim arm and 21 on the filgrastim arm. The median interval of neutrophil engraftment for tbo-filgrastim was 12 days compared to 11 for filgrastim (p=0.178); the median interval of platelet engraftment was 17 days for both arms (p=0.238).Mobilization, collection, toxicity, and engraftment data are summarized in Table 1.Conclusion: Tbo-filgrastim appears to be similar to filgrastim for ASCT mobilization in patients with MM or NHL. Planned study enrollment is 100 evaluable patients; updated study results will be presented.Table 1Tbo-FilgrastimFilgrastimPB CD34+/mcl on Day 41(median & range)20 (4-68)22 (1-115)PB CD34+/mcl on Day 5 (median & range)94 (18-187)92 (11-314)CD34+/kg x106 yield on Day 5 (median & range)10.9 (1.4-21.2)12.0 (1.3-28.4)CD34+/kg yield >2.0 on Day 596%92%CD34+/kg yield >5.0 on Day 575%76%CD34+/kg yield >2.0 in < 4 days100%100%CD34+/kg Yield >5.0 in < 4 days96%92%Post-ASCT EngraftmentDays to Neutrophil Engraftment (median & range)12 (10-20)11 (10-13)Days to Platelet Engraftment (median & range)17 (13-23)17 (13-22)1-Prior to plerixafor dose DisclosuresVij:Celgene, Onyx, Takeda, Novartis, BMS, Sanofi, Janssen, Merck: Consultancy; Takeda, Onyx: Research Funding. Abboud:Teva Phamaceutical: Research Funding.

Pegfilgrastim 6 Mg Versus 12 Mg for Autologous Stem Cell Mobilization in Multiple Myeloma Patients: Efficacy, Safety, and Cost Analysis

▪Background: Autologous hematopoietic cell transplantation (aHCT) is an established treatment for many multiple myeloma (MM) patients. Previous studies have shown pegfilgrastim (PEG) to be a superior hematopoietic cell mobilizing agent in autologous donors in the setting of "just in time" use of plerixafor in patients who don't reach optimal CD34+ in peripheral blood prior to apheresis (PB-CD34+) with filgrastim alone. While most experience is based on PEG 12 mg, we hypothesized that PEG 6mg would lead to similar efficacy and be more cost effective than PEG 12 mg, leading to a practice change in 2014. We have conducted a retrospective analysis comparing the performance of PEG 12 mg (pre change) and PEG 6 mg (post change) for mobilization of hematopoietic progenitor cells in patients with MM at MUSC.Methods: During the period covered in the analysis (Feb 2013 to June 2015) all MM patients undergoing first mobilization received PEG with initiation of apheresis on the 4th day if PB-CD34+ ≥ 25/mm3. Otherwise patients received plerixafor 240 µg/kg in the evening of the 4th day and started collection on the 5th day. Daily apheresis was continued until a target of 6 x 106 CD34+/Kg was met, limiting toxicities developed, or the patient completed 4 apheresis sessions. In the data analysis, patients were divided based on the dosage of PEG received, 12 mg or 6 mg, and the following information was collected: demographics, date of start of mobilization, number of apheresis days, apheresis yield (CD34+cells/kg), "just in time" use of plerixafor, date of transplantation, time to neutrophil and platelet engraftment, and length of hospital stay,. Mobilization costs included PEG US$ 2290 for a 6-mg vial and plerixafor US$ 5350 for a 24-mg vial (PHS pricing). The daily charges associated with apheresis were based on our program's historical charges of US$ 6922.00 per day of apheresis.Results: A total of 119 MM patients undergoing upfront mobilization were identified, with 62 patients receiving PEG 6 mg and 57 patients receiving PEG 12 mg. There were no statistical differences in the age, gender, BMI distributions and prior use of lenalidomide between the patients in PEG 6 mg group versus 12 mg group. The proportion of patients in the 6mg group receiving plerixafor (62.9%) was not statistically different from that of patients in the 12mg group (56.1%) (p= 0.5). There was no statistically significant difference in the distribution of CD34+ apheresis yield between the 6mg group (8x106) versus the 12 mg group (7.4x106) (p= 0.2) or in the proportion of patients reaching the CD34+ target in the 6mg (85.4%) compared with 12 mg group (73.7%) (p= 0.1). In addition, no significant difference was detected in the average time to ANC engraftment (15 days for both) or platelet engraftment (21 days for both) between the two groups. Mean duration of hospitalization was 5 days in both arms (p= 0.7), and no major complications or drug toxicities were identified. No statistical difference was noted in the number of apheresis days (6 mg: 1.8 vs 12 mg: 1.7) between both groups (p= 0.3). The median total cost of collection per patient was lower in the PEG 6 mg group at US$ 16134 versus US$ 18424 in PEG 12 mg group. Interestingly, the mean age of patients who required plerixafor (64 years) was significantly higher than that of patients who did not require plerixafor (57 years) (p-value=0.00).Conclusion: The use of PEG 6mg for autologous hematopoietic cell mobilization in MM patients is more cost-effective and yields similar results when compared with the use of PEG 12 mg. There is no significant correlation between the use of plerixafor and the dosage of PEG used. Plerixafor tends to be more utilized by older patients in both groups. Overall, this single institution study provides rationale for the use of PEG 6 mg instead of PEG 12 mg for CD34+ mobilization in MM patients. DisclosuresOff Label Use: We are studying pegfilgrastim 6mg which is an off-label dosage use for this drug. . Stuart:Sunesis: Honoraria, Other: Advisory Board, Research Funding; Astellas Pharma, Inc: Research Funding.