Plerixafor On Demand Associated With Chemotherapy and G-CSF: Interim Analysis Of a Prospective Study Shows Significant Improvement In PBSC Mobilization and Harvest With No Increase In Costs

Background To date, no prospective study on Plerixafor “on demand” in association with chemotherapy and G-CSF has been reported. Methods We present an interim analysis of the first prospective study in which Plerixafor (PLX) was administered “on demand”, according to a specific algorithm, in patients affected by Multiple Myeloma and Lymphoma who received high dose Cyclophosphamide (4g/m2) or DHAP plus G-CSF to mobilize PBSC. Algorithm was developed after a retrospective study done in our Institution (Blood Transfusion, 11(1):94). One hundred and twelve patients were registered in this prospective study, 111 patients were assessable for requirement of on demand PLX, 102 patients were evaluable for mobilization efficacy of“ PLX on demand” strategy, (72 patients were affected by MM and 30 by Lymphoma). A set of 240 patients receiving the same mobilizing chemotherapy (DHAP or CTX 4 gr/sqm) plus G-CSF were retrospectively studied for comparison. Results PLX requirement, overall, was 14.4% (16/111). PLX requirement was 21.6% in Lymphoma patients and 10.6% in MM patients (p=0.010). Failure to mobilize CD34+ cells in PB (CD34+ peak in PB < 20 x 10^6/l) was reduced by “on demand” strategy compared to conventional mobilization; from 13.0% to 3.0% (p=0.004). Failure to harvest CD34+cells (CD34+< 2x10^6/Kg) decreased from 20.9% to 4.0% (p=0.0001). Second mobilization rate in the “on demand” strategy compared to conventional mobilization decreased from 14.3% to 3.0% (p=0.03). In lymphoma stratum the “on demand strategy” resulted in a successful mobilization in 96.6% while the historical control group had a mobilization successful rate of 73.2% (p=0.007); in the MM stratum the “on demand strategy” was successful in 97.2% while the historical control had a mobilization success of 91.3% (p=0.09). Negative Predictive Value (NPV) of the algorithm was determined in patients treated in the “on demand study” by evaluating the subgroup of patients who received the planned mobilization and did not receive PLX because, according to the algorithm, its use was not indicated. 93 patients were assessable, 93/93 had a successful mobilization (CD34+ in PB > 20x10^6/l), thus NPV was 100%. Positive Predictive Value (PPV) of algorithm was determined in the subgroup of patients who were not treated because of drug shortage although the use of PLX was indicated (n 6). PPV was 83.4%. Of the 10 patients where PLX use was indicated and who received at least one dose, a successful mobilization was reached in 70% (7/10) of cases and a successful harvest in 66.6% (6/10). We estimated the cost of mobilizing and harvesting 100 patients affected by Lymphoma or Myeloma by either conventional mobilization based on chemotherapy plus G-CSF or by the PLX on demand strategy. Sum of cost of first mobilizations and of salvage mobilizations (required in patients failing the first mobilization attempt) were calculated in the two different mobilization strategies. Cost to mobilize 100 Myeloma patients was: 465,648 euros for conventional mobilization versus 423,816 euros for “on demand PLX” strategy; cost to mobilize 100 Lymphoma patients was 552,480 euros in conventional strategy versus 537,912 for “on demand PLX” strategy. Conclusion In association with CTX or DHAP plus G-CSF, the “on demand” use of Plerixafor in patients selected by our algorithm showed a significant improvement in mobilization of CD34+ cells and in harvest of PBSC with no increase in overall costs. Disclosures: No relevant conflicts of interest to declare.

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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

Blood ◽

10.1182/blood.v118.21.4399.4399 ◽

2011 ◽

Vol 118 (21) ◽

pp. 4399-4399

Author(s):

Patrycja Zielinska ◽

Malgorzata Krawczyk-Kulis ◽

Miroslaw Markiewicz ◽

Anna Koclega ◽

Robert Liwoch ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Autologous Stem Cell Transplantation ◽

Conflicts Of Interest ◽

Control Group ◽

High Dose ◽

Standard Regimen ◽

Cd34 Cells

Abstract Abstract 4399 Autologous 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.

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Results and Cost Effectiveness of "on-Demand" Plerixafor Added to Chemotherapy and Granulocyte Colony-Stimulating Factor for Peripheral Blood Stem Cell Mobilization in Multiple Myeloma

Blood ◽

10.1182/blood.v126.23.4305.4305 ◽

2015 ◽

Vol 126 (23) ◽

pp. 4305-4305

Author(s):

Giuseppe Milone ◽

Massimo Martino ◽

Annalia Di Marco ◽

Salvatore Leotta ◽

Andrea Spadaro ◽

...

Keyword(s):

Cost Effectiveness ◽

High Dose Chemotherapy ◽

Control Group ◽

High Dose ◽

On Demand ◽

Cd34 Cells ◽

Optimal Harvest ◽

Increase In Probability ◽

Cell Mobilization ◽

Pbsc Mobilization

Abstract The failure of peripheral blood stem cell (PBSC) mobilization and harvest is a critical issue for multiple myeloma (MM) patients undergoing high-dose chemotherapy. Plerixafor (PLX) is an effective mobilizing agent; however, its use for every MM patient undergoing high-dose chemotherapy has led to a notable increase in costs. We designed a highly specific and sensitive algorithm for identifying patients likely to fail PBSC mobilization after chemotherapy and G-CSF (Blood Transfusion 2013.11:94). The use of this algorithm thereby allows selective administration of PLX to patients predicted to fail mobilization after chemotherapy and G-CSF (on-demand PLX) and may reduce failure rate of PBSC mobilization while limiting cost. We performed a multicenter phase II prospective study of on-demand PLX used according to our algorithm for patients with lymphoma or MM, who were mobilized by cyclophosphamide and G-CSF. The study was powered to demonstrate a reduction in mobilization failure from 14% to 7% for the entire population of treated patients. Here, we report the final results for MM patients. The inclusion criteria for MM patients were as follows: diagnosis of symptomatic MM, age 18-70 yr, achievement of any response after first-line treatment administered for 4-8 months, first mobilization attempt, cardiac and pulmonary function adequate for high-dose chemotherapy. Mobilization schedule was cyclophosphamide (CTX, 4 g/m2) and G-CSF (5-10 mcg/Kg), PLX (240 mcg/Kg) was administered only to patients selected by the algorithm. Estimation of costs was performed according to a previously reported study (BJH 2014, 164, 113). There were 111 patients with MM who underwent treatment. Successful CD34+ cell mobilization (>20×109 cells/mL in PB) was achieved for 97.2% (108/111) of patients, and failure of mobilization occurred in the remaining 3 (2.8%); minimal apheretic harvest success (>2.0×106 CD34+ cells/Kg) was achieved for 97.2% (108/111); and optimal harvest success (=/>4.0×106 CD34+ cells/Kg) was achieved for 84.6% (94/111). On-demand PLX was needed for 8.2% of patients (9/111). After autologous hematopoietic transplantation, neutrophil (N) engraftment (N>0.5x109 cells/L) was reached at day +11.8 (range day +8 to +24). We compared these prospective results with the mobilization results obtained retrospectively in a control group of 183 MM patients who received the same mobilization schedule without PLX. After the two groups were adjusted for unbalanced factors, multivariable logistic regression analysis revealed that on-demand PLX treatment according to the algorithm led to significant increases in the probabilities of achieving a successful minimal apheretic harvest (p=0.006; hazard ratio [HR] 5.624, 95% confidence interval [CI] 1.168-19.548) and optimal harvest (p=0.02; HR 2.121, 95% CI 1.118-4.025). The mean cost increase for the first mobilization in the PLX-on-demand prospective study, in respect to control group, was 615 €/patient. The incremental cost-effectiveness ratio (ICER) was calculated as: (cost1-cost2)/(result1-result2). ICER was 47 €/1% increase in probability of a minimal apheretic harvest while it was 68 €/1% increase in probability of an optimal apheretic harvest. In conclusion, the final analysis of our study found that on-demand PLX for MM patients, which was added to the mobilization schedule of CTX (4 g/m2) + G-CSF (5-10 mcg/Kg), allowed a successful harvest from the first mobilization treatment in > 97% of patients, with 85% of patients achieving a harvest sufficient for two rounds of high-dose chemotherapy. These results indicate that on-demand PLX added to mobilization chemotherapy is a significant improvement over the same type of mobilization chemotherapy without PLX. The limited use of PLX in this study allowed for a favorable incremental cost-effectiveness ratio of this expensive agent. On-demand PLX used according to a validated algorithm in addition to CTX plus G-CSF may be considered a new standard for PBSC mobilization and harvest in patients with MM. Table 1.Failure of CD34+ Mobilization in PB Failure of Minimal Harvest Failure of Optimal Harvest Cost per PatientICER (Minimal Harvest)ICER (Optimal Harvest)PLX on Demand (n 111)2.8%2.8%15.4%3,969 €47 €/ 1% increase in probability of a Minimal Harvest68 €/ 1% increase in probability of an Optimal HarvestControl Cohort (n 183)7.6%15.8%24.4%3,354 €P (adjusted for comparisons)NS0.0060.02 Disclosures Milone: Sanofi: Consultancy. Martino:Sanofi: Consultancy. Olivieri:Sanofi: Consultancy.

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

Blood ◽

10.1182/blood.v124.21.1193.1193 ◽

2014 ◽

Vol 124 (21) ◽

pp. 1193-1193

Author(s):

Jaakko Valtola ◽

Ville Varmavuo ◽

Antti Ropponen ◽

Marja Pyörälä ◽

Anne Nihtinen ◽

...

Keyword(s):

Stem Cells ◽

Flow Cytometry ◽

Prospective Study ◽

Nk Cells ◽

Immune Reconstitution ◽

Control Group ◽

Immune Recovery ◽

Cellular Composition ◽

Cd34 Cells ◽

Significant Difference

Abstract 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 1. Cellular composition of freezed grafts of NHL patients mobilized with or without plerixafor. Mobilization with plerixafor (n = 14) Mobilization without plerixafor (n = 17) P - value Blood 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+NK 2.1 (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) 0,0070.0360.6200.0010.0010.0010.0030.1920.001 7AAD = 7-Aminoactinomycin D w/a = without w = with Disclosures Jantunen: Sanofi: Employment.

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The More Effective and the More (bio) Similar: Plerixafor and Filgrastim XM02 (tevagastrim) As First Line PBSC Mobilization Strategy in Patients with Multiple Myeloma and Lymphomas Candidate to ABMT

Blood ◽

10.1182/blood.v118.21.2994.2994 ◽

2011 ◽

Vol 118 (21) ◽

pp. 2994-2994

Author(s):

Daniele Laszlo ◽

Giovanna Andreola ◽

Aleksandra Babic ◽

Mara Negri ◽

Cristina Rabascio ◽

...

Keyword(s):

Stem Cells ◽

Multiple Myeloma ◽

Conflicts Of Interest ◽

Median Number ◽

High Dose Chemotherapy ◽

European Medicines Agency ◽

High Dose ◽

First Line ◽

Adequate Number ◽

Cd34 Cells

Abstract Abstract 2994 Patients affected by hematologic malignancies might benefit from high dose chemotherapy followed by peripheral stem cells (PBSC) transplant. Chemotherapy in combination with G-CSF is effective in mobilizing stem cells but often toxic, might require prolonged hospitalization and extensive supportive care. Moreover a high proportion of patients, ranging from 11 to 53%, fail to collect an adequate number of stem cells with this approach. In this setting plerixafor, a CXCR4 chemokine antagonist, has shown to increase the number of circulating CD34+ cells in cancer patients when used alone or with G-CSF and to be able to rescue patients unable to mobilize with traditional regimens. Recently, several forms of biosimilar nonglycosylated recombinant human G-CSF have been clinically developed and approved by the European Medicines Agency for the same indications as the reference filgrastim product on the basis of comparable quality, efficacy, and safety. Biosimilars also provide a more cost-effective strategy and their use in clinical setting may provide cost savings in their indicated uses. From December 2010 to July 2011, 16 patients, median age 55 (19–67), affected by Non-Hodgking Lymphoma (6), Hodgking Disease (2) and MM (8), received a combination of biosimilar version of G-CSF (Tevagrastim) and plerixafor in order to mobilize PBSC as first line strategy. Tevagrastim was self-administered (10μg/kg/die) for 3 days; on day 4 patients were admitted to the hospital, circulating CD34+ cells counted and if >20 cells/μl, plerixafor was administered (0.24mg/kg) 12 hours before the scheduled apheresis. There were 7 males and 9 females, median lines of previous chemotherapy was 1(1–4). Median number of circulating CD34+ cells on day 4 was 16 (8–42). Plerixafor was administered to all but 1 patients who had already 42 CD34+ cells/μl on day 4. On day 5, after plerixafor administration median number of circulating CD34+ cells had raised to 68/μl (18–138). All the patients underwent leukapheresis and were able to collect an adequate number of CD34+ cells necessary for the transplantation procedure with a median number of 5.2 ×106 (2.2–10.6) CD34+cells/kg in a median number of 1 procedure (1–2). For patients with Multiple Myeloma, 6/8 patients were able to collect a median of 5.8×106 CD34+/kg (4.2–10.6) in a single procedure. No major side effect was observed. So far, 7/16 patients underwent high dose chemotherapy followed by PBSC transplant. Engraftment occurred in all patients with a time to ANC>500 of 12 (9–13) and of PLT>20.000 of 13 (9–19) days. The combination of tevagrastim and plerixafor is safe and effective in mobilizing PBSC and allows a collection of a more than adequate number of cells in most of the patients in a maximum of 2 apheresis procedure, even in patients with MM who need to collect a double amount cells. Disclosures: No relevant conflicts of interest to declare.

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Remobilization with High Dose Methotrexate and Cytarabine in Patients with Non-Hodgkin Lymphoma and Multiple Myeloma Previously Failing Mobilization with Chemotherapy and Cytokine Treatment

Blood ◽

10.1182/blood.v118.21.4402.4402 ◽

2011 ◽

Vol 118 (21) ◽

pp. 4402-4402

Author(s):

Seong Joon Park ◽

Dok Hyun Yoon ◽

Shin Kim ◽

Cheolwon Suh

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Conflicts Of Interest ◽

Total Yield ◽

Chemotherapeutic Agents ◽

High Dose ◽

High Dose Methotrexate ◽

Chemotherapeutic Regimen ◽

Dose Methotrexate ◽

Cd34 Cells

Abstract Abstract 4402 Background High-dose chemotherapy supported by autologous stem cell transplantation is a widely used therapeutic modality especially in patients with non-Hodgkin lymphomas (NHL) and multiple myeloma (MM). However, mobilization failure rates following first attempt are estimated to be between 5% and 30% and remobilization is required in those patients. Although plerixafor, a selective CXCR4 antagonist, is a promising agent for these purpose, mobilization with chemotherapeutic agents would be a hands-on option.°° Therefore we investigated the feasibility of high dose methotrexate and cytarabine with G-CSF as a remobilization regimen in those who failed a prior mobilization and collection with chemotherapy and G-CSF. Patients and methods Mobilization failure was defined as a collection of less than 5 × 106 CD34+ cells after 3–5 apheresis procedures. Methotrexate (3,500 mg/m2 in a 120 min infusion) on day 1 and cytarabine (3,000 mg/m2 infusion for 120 min) on day 4 and day 5 were followed by G-CSF. Supportive care and leucovorine rescue were done as standard protocol. Peripheral blood (PB) hematopoietic progenitor cells (HPCs) were counted with the Sysmex SE9000. PB progenitor cell harvest was initiated when HPC levels reached at least 5 per mm3. Results Total 8 patients (6 NHL and 2 MM, median age: 55 years) who have failed in previous mobilization with conventional chemotherapy and G-CSF were tried again with high dose methotrexate, cytarabine and G-CSF. (table 1) Successful collection of CD34+ cells (> 5 × 106/kg) was achieved in six patients (75%). The total yield of CD34+ cells per kg of body weight harvested by 3 to 5 apheresis procedures was 6.28 × 106/kg (median; range, 1.53– 10.09 × 106/kg). (table 2) Conclusion High dose-MTX and cytarabine plus G-CSF may be a feasible chemotherapeutic regimen for stem cell mobilization in NHL and MM patients who have failed in previous mobilization with other type of chemotherapy and G-CSF. Disclosures: No relevant conflicts of interest to declare.

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Autologous Stem Cell Collection In Lymphoma and Myeloma Patients: Single Center Analysis With Intention To Successful Mobilization and Collection Under Restricted Permission For Use Of Plerixafor

Blood ◽

10.1182/blood.v122.21.5443.5443 ◽

2013 ◽

Vol 122 (21) ◽

pp. 5443-5443

Author(s):

Baris Hasbal ◽

Hulya Bilgen ◽

Tulay Ozcelik ◽

Fehmi Hindilerden ◽

Serkan Guvenc ◽

...

Keyword(s):

Stem Cell ◽

Hematopoietic Stem Cell ◽

Conflicts Of Interest ◽

Single Agent ◽

Previous Treatment ◽

Autologous Bone Marrow ◽

Close Correlation ◽

High Dose ◽

Hematopoietic Stem ◽

Cd34 Cells

Abstract High dose chemotherapy (HDCT) with autologous hematopoietic stem cell transplantation (HSCT) rescue is a potentially curative&consolidative therapy for advanced hematological malignancies, and it also permits the administration of higher doses of chemotherapy to overcome tumor cell resistance. In this study, our aim is to evaluate 167 consecutive myeloma (MM) and lymphoma (ML) patients referred to our center between August 2010 and May 2013. Patients data are analyzed in intent to successful hematopoietic stem cell (HSC) mobilization and collection. In our country we have limited access to plerixafor, as salvage HSC mobilizing agent, permitted only after a failed mobilization&collection trial of chemotherapy and G-CSF. Our center's policy is to collect HSC with G-CSF in all MM (exception of prolonged revlimide use and prior autologous HSCT), and non-heavily pretreated ML patients. Candidates for poor mobilization underwent first CT and G-CSF, and second line receive plerixafor. Under these circumstances 86 lymphoma patients (31 Hodgkin and 55 NHL) and 81 MM patients (F/M: 57/110, med. age 52, range 18-72) were included in this study. Nearly >15% of the patients received more than 2 cycles of chemotherapy before HSC collection. Mobilization with G-CSF as a single agent resulted in optimal CD34+ cell yield for 121 (72%) patients. In myeloma G-CSF as first line resulted with 92.7% successful HSC mobilization and collection. Overall 17 patients received plerixafor as 2nd or 3rd line, and resulted with sufficient HSC collection in 57.3%. In three cases (MM:1, ML:2) additional support with autologous bone marrow collection necessary. Only in 9 (5.3%) patients all attempts for mobilization failed including plerixafor. After any type of mobilization regimen median count for pCD34+ cells obtained was 18/mcl. Median yield of 3.3 x 106/kg CD34+ cells/kg was collected with range of 0.2-33.9x106/kg in total apheresis sessions. MM patients have significant high levels of preapheresis circulating CD34+ count in comparison to ML patients (29 vs 15, p=0.001). pCD34+ cell did not correlate with body mass index, age, underlying disease and previous treatment cycles. There is a close correlation between pCD34+ cell count and collected CD34+ cells in all types of mobilization regimens as G-CSF, chemotherapy and plerixafor (relatively; p<0.001, p=0.002 and p=0.001). Successful ASCT is achieved in 144 patients transplanted so far. Mobilization is achieved in almost all multiple myeloma patients and most of lymphoma patients with only G-CSF based regimen in our cohort. Half of patients not mobilized with G-CSF were successfully mobilized with chemotherapy and plerixafor as second or third line regimen. The restricted use of plerixafor resulted in time and expense for additional chemotherapy and collection attempt, whereas this inconvenience did not impact the success of stem mobilization and collection in our current policy within 3 years. Disclosures: No relevant conflicts of interest to declare.

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Outpatient Hematopoietic Grafting in Patients with Multiple Sclerosis Employing Autologous Non-Cryopreserved Peripheral Blood Stem Cells: A Feasibility Study

Blood ◽

10.1182/blood.v126.23.5489.5489 ◽

2015 ◽

Vol 126 (23) ◽

pp. 5489-5489

Author(s):

Guillermo J. Ruiz-Arguelles ◽

Andrés León-Peña ◽

Emilio Medina-Ceballos ◽

Alejandro Ruiz-Arguelles ◽

Manuel A Ruiz-Delgado ◽

...

Keyword(s):

Multiple Sclerosis ◽

Stem Cells ◽

Peripheral Blood ◽

Conflicts Of Interest ◽

High Dose ◽

Outpatient Basis ◽

Peripheral Blood Stem Cells ◽

Hematopoietic Stem ◽

Cd34 Cells ◽

Blood Stem Cells

Abstract Background: Multiple sclerosis (MS) is a chronic, inflammatory, debilitating disease that causes destruction of central nervous system (CNS) myelin, with varying degrees of axonal damage. With the goalofd re-setting the immune system, autologous hematopoietic stem cell transplantations (HSCT) have been done in patients with MS since 1996 and more than 700 HSCTs have been performed around the world. The risk of transplant related mortality in HSCT for MS has declined over the past years. Material and methods: Consecutive patients with MS were autografted in a single center using: Hematopoietic stem cells (HSC) were mobilized with cyclophosphamide (Cy), 3 gr/m2 and G-CSF, the procedure was conducted on outpatient basis employing peripheral blood non-frozen HSC and conditioning with high-dose Cy (100 mg/Kg) and post-transplant G-CSF and rituximab. Antibiotics, antimycotics and antivirals were given orally. Results: Thirteen patients with MS were prospectively accrued in the study. There were 7 females and 6 males. Median age was 48 years, range 24 to 65. The expanded disability status scale (EDSS) score of these patients had a median of 5 points (range 1 to 6). All the autografts were started on an outpatient basis and two persons were admitted to the hospital during the procedure (persistent nausea/vomiting and neutropenic fever); they stayed in the hospital for 48 hours. In order to obtain a minimum of 1 x106 viable CD34+ cells/Kg, one to four apheresis were done (median 1). The total number of viable CD34+ cells infused to the patients ranged between 1 and 9.6x106 (median 3.1). Patients recovered above 0.5 x109/L absolute granulocytes on median day 9 (range 6 to 12). No individuals needed transfusions of red blood cells nor platelets transfusions. There were no transplant-related deaths and the 23-month overall survival of the autografted patients is 100%. Median cost of the procedure was 30 000 USD. In 8 persons the EDSS was assessed three months after the graft; it diminished from a median of 4.5 to a median of 2.5. In 5 patients, the three months re-assessment of the EDSS has not been possible as a result of the time elapsed after the autograft. Discussion: These data indicate that it is possible to conduct autotrasplants for patients with MS employing a simplification of the conventional procedures by means of non-frozen peripheral blood stem cells and outpatient conduction. Additional information is needed to asses the efficacy of these procedures in the treatment of patients with MS. Disclosures No relevant conflicts of interest to declare.

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Appropriate Timing of G-CSF Use After Mobilization Chemotherapy Significantly Increases the Yield ofCD34+ Cells in autoPBSCT.

Blood ◽

10.1182/blood.v114.22.2144.2144 ◽

2009 ◽

Vol 114 (22) ◽

pp. 2144-2144

Author(s):

Li Xu ◽

Chunkang Chang ◽

Xiao Li

Keyword(s):

Multiple Myeloma ◽

Peripheral Blood Stem Cell ◽

Conflicts Of Interest ◽

Alkylating Agents ◽

Control Group ◽

Subcutaneous Dose ◽

Group 12 ◽

Cd34 Cells ◽

Wbc Count ◽

Experimental Group

Abstract Abstract 2144 Poster Board II-121 The yield of CD34+ cells collected by apheresis for autologous peripheral blood stem cell (PBSC) transplantation was greatly increased when the appropriate timing was determined to begin using G-CSF after COAEP mobilization. 29 patients with lymphoma or multiple myeloma (MM) received the same mobilization chemotherapy, including CTX 400mg/m2 d1; VDS 2 mg/ m2 d1; Ara-C 60 mg/m2 ×5d; vp-16 60 mg/m2 ×5d; and prednisone 40 mg/m2 ×5d. The control group (12 cases) received subcutaneous G-CSF (filgrastim) at the first restoration after the initial nadir of the peripheral WBC count. The experimental group (17 cases) received G-CSF during the steady rise of the WBC count (end of fluctuating after initial nadir). G-CSF was given in a single daily subcutaneous dose of 300μg until the final PBSC apheresis.When the peripheral WBC and mononuclear cell (MNC) counts reached 10.0×109/Land 1.0×109/L, respectively, leukapheresis was carried out using the COBE Spectrablood cell separator. Despite comparable treatment with alkylating agents, a significantly increased yield of CD34 positive cells was observed in the experimental group (32.0×106/kg) compared to the control group (3.1×106/kg) (P=0.0182). This result indicates the importance of appropriate timing for the use G-CSF after mobilization chemotherapy to increase the CD34+ cell yield. Disclosures: No relevant conflicts of interest to declare.

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Addition of Rituximab to Chemotherapy Alters the Prognostic Impact of Tumor-Associated Macrophages in Diffuse Large B-Cell Lymphoma

Blood ◽

10.1182/blood.v118.21.2650.2650 ◽

2011 ◽

Vol 118 (21) ◽

pp. 2650-2650

Author(s):

Sari Riihijärvi ◽

Maria Pöyhönen ◽

Minna Taskinen ◽

Marja-Liisa Karjalainen-Lindsberg ◽

Sirpa Leppä

Keyword(s):

De Novo ◽

Conflicts Of Interest ◽

Progression Free Survival ◽

B Cell Lymphoma ◽

High Dose Chemotherapy ◽

Control Group ◽

High Dose ◽

Prognostic Impact ◽

Tumor Associated Macrophages ◽

Kaplan Meier

Abstract Abstract 2650 Background: Tumor associated macrophages (TAM) have at least two potential roles in promoting tumor growth: suppression of immune responses and potentiation of angiogenesis. In numerous cancer types, including lymphomas, high M2 type TAM content has been associated with worse prognosis. Rarely, high TAM content correlates with better survival. We have recently shown that CD68 positive TAMs in DLBCL contribute to unfavorable survival after high dose chemotherapy. Here we have extended our analyses on M2 type macrophages and questioned how combination of rituximab with chemotherapy influences TAM-associated clinical outcome. Patients and Methods: Expression of CD163 and CCL18, which are primarily expressed in M2 type macrophages, were identified immunohistochemically from samples of 101 de novo DLBCL patients treated with rituximab in combination with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone)-like regimen (immunochemotherapy). With a median follow-up of 65 months, (range 16–114 months), 5-year progression free survival (PFS) was 70% and overall survival (OS) 73%. 29 DLBCL patients previously treated with up front high dose chemotherapy served as a control group. Results: Correlation between CD163 and CCL18 positive TAMs was found (rs=0.427, p<0.001). In the Kaplan-Meier analyses the cutoff level of 67% was found to best discriminate between subgroups with different outcomes. Consistent with previous data, chemotherapy-treated patients with high CD163 or CCL18 positive TAM counts displayed a significantly inferior OS and PFS than the low group (Table). In contrast, after rituximab containing regimen, the patients with high CD163 and CCL18 positive TAM content tended to have favorable survival. Among the patients with low counts in both CD163 and CCL18 positive TAMs, PFS and OS were found to be significantly worse in comparison to others. Conclusions: In contrast to data on chemotherapy treated DLBCL or other lymphoma types, M2 type TAM content is associated with favorable prognosis in DLBCL patients after immunochemotherapy. Disclosures: No relevant conflicts of interest to declare.

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Utility of Second and Subsequent Peripheral Blood Stem Cell (PBSC) Mobilization in Myeloma Patients

Blood ◽

10.1182/blood.v118.21.4401.4401 ◽

2011 ◽

Vol 118 (21) ◽

pp. 4401-4401

Author(s):

Samar Kulkarni ◽

Adrian JC Bloor ◽

Mike Dennis ◽

Dianne Sweeney ◽

Rita Angelica ◽

...

Keyword(s):

Induction Therapy ◽

Peripheral Blood ◽

Conflicts Of Interest ◽

High Dose ◽

Chemotherapy Response ◽

Single Centre ◽

Peripheral Blood Stem Cells ◽

Entire Cohort ◽

Cd34 Cells ◽

Pbsc Mobilization

Abstract Abstract 4401 Standard therapy for myeloma includes induction therapy followed by high dose melphalan and autograft (HDM/autograft). Safe delivery of HDM requires optimum peripheral blood stem cells (PBSC) as quantitated by CD34 expression. In ability to collect sufficient PBSC is not uncommon and efficacy of subsequent harvest after failed first attemp needs evaluation. In this single centre analysis, 62 patients with myeloma treated at our centre between 1997 and 2009 were analysed to assess the results of second and subsequent harvest and the factors predictive of failure to mobilize CD34 cells more than 2×10^6/kg. 40 patients were male and 22 were females with a median age of 57 yr. (range: 41–68, M:56yr. Vs. F: 58 yr., p=0.6) Before first harvest patients received induction therapy with either VAD (or similar) chemotherapy to maximum response (n=46), thalidomide combination (n=15) or combination (n=2) and only 2 patients had exposure to Melphalan. 49 patients (78%) achieved at least PR with induction therapy. For the first harvest mobilization was attempted with Cyclo/GCSF (n=56), ESHAP (n=5) and GCSF alone (n=1) at a median interval of 38 days from finishing induction (range: 15–535). Median CD34 yield after first attempt was 1.7×10^6/kg (range: 0.04–14.6) in 1 (n=52) or 2 (n=10) collects. 28 patients (45%) achieved yield more than 2. Yield was slightly lower in female patients (1.39 vs. 2.58, p=0.074) but there was no effect of age, type of chemotherapy, response or mobilization regimen. 28 patients had back to back mobilization with either Cyclo/GCSF or ESHAP priming at a median of 35 d from first harvest (range: 11–99) and the median CD34 yield was 1.7(range: 0.03–14.7) in 1(n=19) or 2 (n=9) collects. All other patients had second harvest at a median of 1018 d(range: 25–2246) and 21 had the collection attempted after HDM/Autograft. The median CD34 yield in the entire cohort of 62 patients was 2.4 (range: 0.03–27.2) and this was achieved in 1(n=45) or 2 (n=17) procedures. Patients who had HDM/autograft (n=21) achieved same yields as others (median: 2.8 vs. 2.2, p=0.11) and required similar number of procedures (median: 1, p=0.62). 26/62 patients (42%) achieved more than 2×10^6 yield in second attempt. Rate was lower in HDM group but not statistically significant (28% vs. 51%, p=0.13). 12/62 (19%) had third attempt at harvest at a median of 862 days from second harvest. The median CD34 yield was 2.3 (range: 0.09–4.13) and 6 (50%) achieved yield more than 2×10^6/kg. There was no correlation between CD34 yield in first and subsequent harvests (R^2: 1.2%). Out of 26 patients who did not collect more than 2 in first attempt, only 9 (35%) managed to achieve this yield in second attempts, especially if they had HDM/autograft. This single centre analysis shows that failure to achieve sufficient CD34 cells in first attempt results in low yields in subsequent tries at PBSC mobilization. If this is a predictor of disease behaviour will be analysed. For patients who may be candidates for more than one HDM procedures efforts to increase the yield in first attempt should be tried. Impact of newer drugs on the attempts at subsequent mobilization needs evaluation. Disclosures: No relevant conflicts of interest to declare.

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