Stem Cell Mobilization after Various Induction Regimens in Patients with Multiple Myeloma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5433-5433
Author(s):  
Jakub Radocha ◽  
Vladimir Maisnar ◽  
Miriam Lanska ◽  
Jiri Hanousek ◽  
Katerina Machalkova ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Conflicts Of Interest ◽  
Rapid Development ◽  
Autologous Transplantation ◽  
Stem Cell Mobilization ◽  
High Dose ◽  
Cell Transplant ◽  
Cell Mobilization ◽  
Stem Cell Collection

Abstract Stem cell mobilization after various induction regimens in patients with multiple myeloma Introduction: Rapid development of novel therapies for multiple myeloma has led to a significant improvement in response to the treatment. Stem cell mobilization before autologous stem cell transplantation is a source of considerable costs of transplant procedure. Whether modern induction regimens affect outcome of stem cell mobilization has not been extensively studied. Aim: The goal of this study was to compare efficacy of stem cell mobilization after different induction regimens in patients with multiple myeloma. The primary goal was to compare CTD (cyclophosphamide, thalidomide, dexamethasone), CVD (cyclophosphamide, bortezomib, dexamethasone) and VTD (bortezomib, thalidomide, dexamethasone) and regimens in terms of succesful stem cell collection. Methods: All patients with multiple myeloma who have been planned for stem cell collection and were treated with one of the above mentioned regimens were included in this retrospective analysis. The demographic data, amount of stem cells collected, number of days needed to reach the target collection were recorded. All patients received high dose cyclophosphamide 2,5 g/m2 prior to stem cell collection and were primed with G-CSF twice daily from day 5. The collection was started at day 10. Collection goal was 8x106/kg CD34+ cells. Results: 15 patients received CTD, 25 patients CVD and 16 patients VTD regimen before stem cell collection. Groups were comparable according to age, gender and myeloma stages. Mean collected cells at the end of collection were 9.2 (SD 2.8) for CTD, 12.3 (SD 5.6) for CVD and 10.1 (SD 2.1) for VTD (p=0.066). Mean daily harvest was 3.4, 8.0 and 7.6 x106/kg respectively (p=0.01). Mean days needed to reach desired harvest were 3, 2.25 and 1.6 days (p=0.001). No collection failure was observed. Conclusion: The best collection results were seen in patients after induction with CVD or VTD regimen. VTD regimen also required the least days for collection and seems to be most beneficial for cost of collection. CTD regimen shows the least efficacy in stem cell collection before autologous transplantation. All patients managed to harvest for at least one stem cell transplant. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

The Optimal Timing for Stem Cell Collection After Induction Therapy for Patients with Multiple Myeloma

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2252-2252
Author(s):  
Aziz Nazha ◽  
Dan T. Vogl ◽  
Una O'Doherty ◽  
Patricia Mangan ◽  
Kathleen Cunningham ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Stem Cell ◽  
Conflicts Of Interest ◽  
Optimal Timing ◽  
High Dose ◽  
Cell Transplant ◽  
Cd 34 ◽  
The Mean ◽  
Stem Cell Collection

Abstract Abstract 2252 Introduction: High dose chemotherapy and stem cell transplant remains an integral part of the therapy for Multiple Myeloma patients under age of 70. The collection of sufficient number of stem cells for one or more transplant is however sometimes a challenge. Moreover, the optimal timing for stem cell collection after induction chemotherapies is controversial. The standard recommendation is for stem cell collection after 4–6 cycles of non-alkylator regimen, however studies to support this practice are limited. Material and Method: We conducted a retrospective analysis of 366 patients who were diagnosed with multiple myeloma and mobilized at the Hospital of University of Pennsylvania between January 2002 and December 2008. Patients who did not meet the initial inclusion criteria were those who had induction regimens containing an alkalytor agent or whose regimens were not well documented and were excluded from futher analysis (85). Every 4 cycles of any non-alkalytor agent was considered to be one treatment session for the purpose of this analysis. 245 patients received 1 or 2 treatment sessions and 36 received > 2. All patients were mobilized with either Cyclophosphamide/G-CSF (CY/G-CSF), Plerixafor/G-CSF (AMD/G-CSF), or G-CSF alone. Result: The mean number of collected CD 34+ cells (CD 34+) was 9.22 × 106 CD34+/Kg in the patients who received 1 or 2 sessions and 6.87 × 1106 CD34+/Kg in the patients who received > 2 sessions (P= 0.005). The number of the patients who collected > 6 × 106 CD34+/Kg was 63%(153/246), 53%(19/36) respectively, (p= 0.005). The patients who mobilized with either CY/G-CSF or AMD/G-CSF collected higher number of CD34+ than the patients mobilized with G-CSF alone in both groups. (Table 1, 2.) The mean number of collected stem cells was 7.14 × 106 CD34+/Kg in the patients who received more than 2 sessions of different regimens and 6.26 × 106 CD34+/Kg in the patients who received > 2 sessions of the same regimen. Conclusion: The patients who mobilized after fewer than 8 cycles of non-alkylator agents (2 sessions) collected a higher number of CD 34+ than those with greater than 8 cycles. CY/G-CSF or AMD/G-CSF are similar and superior to G-CSF alone in the more heavily treated patients. The patients who received multiple sessions of the same regimen have similar outcome compared to those who received multiple different regimens suggesting that the duration of the treatment may impact stem cell collection more than the content of the regimen. Prospective studies in this regards are warranted. Disclosures: No relevant conflicts of interest to declare.

Plerixafor and G-CSF Versus Cyclophosphamide and G-CSF for Stem Cell Mobilization in Patients with Multiple Myeloma.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2146-2146 ◽  
Author(s):  
Aziz Nazha ◽  
Rachel Cook ◽  
Dan T. Vogl ◽  
Patricia A. Mangan ◽  
Kimberly Hummel ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Stem Cell ◽  
Incomplete Data ◽  
Median Number ◽  
Stem Cell Mobilization ◽  
Cell Transplant ◽  
Long Term Outcome ◽  
Cell Mobilization ◽  
Stem Cell Collection

Abstract Abstract 2146 Poster Board II-123 Introduction: High dose melphalan and autologus stem cell transplant remains an effective treatment for patients with either early or refractory multiple myeloma (MM). Collection of sufficient numbers of stem cells for more than one transplant is optimal. G-CSF with chemotherapy, particularly cyclophosphamide (CY/G-CSF), has been a widely used and effective regimen for stem cell collection in MM. Plerixafor, a CXCR4 antagonist, when combined with G-CSF has been shown in a large randomized clinical trial to be superior to G-CSF alone. A comparison of plerixifor/G-CSF to CY/G-CSF is presented here. Materials and Methods: We performed a single institution retrospective analysis of 365 patients with MM who underwent stem cell mobilization and harvest at the University of Pennsylvania Abramson Cancer Center from January 2002 to December 2007. All patients were harvested early in the course of their disease. 76 patients were excluded from this analysis (23 had incomplete data on induction regimen, 19 had incomplete data on stem cell collection, 16 had incomplete data on mobilization regimen, 10 underwent allogeneic transplants, 2 had bone marrow rather than peripheral blood harvests, 2 had stem cells collected at an outside institution, 2 had chemotherapy mobilization other than CY and 2 had medical complications prior to harvest and after mobilization). Therefore, 289 patients were included in the analysis; 16 received plerixafor/G-CSF, 198 received CY/G-CSF, and 75 received G-CSF alone. Results: The median number of collected stem cells was 7.95 × 106 CD34+/kg in plerixafor/G-CSF group, 7.7 × 106 CD34+/kg in Cy/G-CSF group and 4.5 × 106 CD34+/kg in G-CSF alone group. The median number of apheresis days was 2 days, 2 days and 4 days respectively. The percentage of the patients who collected ≥ 6 × 106 CD34+/kg in < 3 apheresis was 63% (10/16), 62% (123/198) and 19% (14/75) respectively. The percentage of the patients who collected ≥ 6 × 106CD34+/kg <5 apheresis was 81% (13/16), 69% (136/198) and 23% (17/75) respectively. The mean CD34+/kg collected erither after CY/G-CSF or plerixafor/G-CSF was higher than G-CSF alone (p<0.0001 for each analysis). Conclusion: This analysis suggests that plerixafor/G-CSF and CY/G-CSF mobilization result in similar and adequate stem cell harvest numbers for autologous stem cell transplantation for MM. Both approaches are superior to G-CSF alone. The choice of plerixafor/G-CSF vs CY/G-CSF for stem cell mobilization will therefore depend on further analysis of the relative costs, toxicities and long term outcome of these regimens. Disclosures: Stadtmauer: genzyme: Consultancy.

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

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2075-2075 ◽  
Author(s):  
Luis Isola ◽  
Karen M Banoff ◽  
Sara S Kim
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Lower Cost ◽  
Conflicts Of Interest ◽  
Practice Change ◽  
Stem Cell Mobilization ◽  
Neutrophil Recovery ◽  
Cd34 Cells ◽  
Cell Mobilization ◽  
Stem Cell Collection

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

Bortezomib Added to the Standard Mobilization Regimen of G-CSF and High-Dose Cyclophosphamide Is a Safe and Effective Combination for a High Yield Stem Cell Collection While Promoting Further Tumor Mass Reduction in Myeloma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2953-2953 ◽  
Author(s):  
Jessica L. Stern ◽  
Brian Di Carlo ◽  
Michael W. Schuster ◽  
Tsiporah B. Shore ◽  
John G. Harpel ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Stem Cell ◽  
Alkylating Agents ◽  
Pegylated Liposomal Doxorubicin ◽  
Stem Cell Mobilization ◽  
High Dose ◽  
Cell Mobilization ◽  
Grade 3 ◽  
Stem Cell Collection

Abstract Standard stem cell mobilization regimens for multiple myeloma patients include G-CSF alone or in combination with high dose cyclophosphamide. Given the known in vitro and in vivo synergy between alkylating agents and proteosome inhibitors, we sought to optimize the potential for concurrent cytoreduction by adding bortezomib to the mobilization regimen. Five evaluable patients, whose prior therapy consisted of six cycles of a 21-day treatment with bortezomib/dexamethasone +/− pegylated liposomal doxorubicin, were mobilized. They received IV push bortezomib at 1.3 mg/m2 on days 1, 4, 8, and 11 in combination with high-dose cyclophosphamide at 3mg/m2 and MESNA on day 8. G-CSF was given for 10 consecutive days starting on day 9. One patient began this regimen in nCR, two were in PR, and two were in CR by urine and serum immunofixation and bone marrow evaluation. Stem cells were easily harvested from each of the five patients. The number of CD34+ cells collected far exceeded the amount normally mobilized with cyclophosphamide and/or G-CSF alone, with four out of 5 patients collected in a single day. The two patients who began the mobilization cycle in PR continued to respond positively. Their protein levels dropped an additional 8.9 and 14.6 percent respectively during the last cycle. The patient who began mobilization in nCR achieved a CR by the end of treatment. Some expected toxicities associated with high dose cyclophosphamide and G-CSF occurred. All patients experienced grade 3 and 4 cytopenias, however, they recovered and were able to continue on to transplant. Serious adverse events of grade 3 chest pain (non-cardiac), grade 4 pneumonia, and grade 4 febrile neutropenia also occurred. Bortezomib in addition to high dose cyclophosphamide followed by G-CSF is a novel, well-tolerated and efficacious combination for stem cell mobilization in patients with multiple myeloma. This regimen not only yields a high number of stem cells within a short collection time, but may further cytoreduce disease as well. Stem Cell Collection Patients Days Required for Collection CD34+ Stem Cells (million/kg) 1 1 21.2 2 1 47.4 3 1 22 4 1 17.9 5 4 40.6

Fractionated High-Dose Cyclophosphamide and G-CSF: An Extremely Effective Chemo-Mobilization Modality In Patients With Multiple Myeloma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4521-4521
Author(s):  
Ahmad Antar ◽  
Zaher K. Otrock ◽  
Nadim El Majzoub ◽  
Nabila Kreidieh ◽  
Muhammad Muhammad ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Febrile Neutropenia ◽  
Median Time ◽  
Stem Cell Mobilization ◽  
Fixed Dose ◽  
High Dose ◽  
Cd34 Cells ◽  
Cell Mobilization ◽  
Stem Cell Collection

Background The optimal stem cell mobilization regimen for multiple myeloma (MM) is undefined. Most centers use either granulocyte-colony stimulating factor (G-CSF) alone (steady state strategy) or cyclophosphamide (CY) followed by G-CSF (chemo-mobilizing strategy). However, the impact of CY dose on stem cell yield and subsequent engraftment, and toxicity is unknown. We retrospectively analyzed our experience using fractionated high-dose CY and G-CSF as our preferred chemo-mobilization strategy in MM patients (pts) and its impact on the mobilization outcomes, engraftment and the observed toxicity. Methods Between 01/2000 and 12/2012, 220 chemo-mobilization attempts were undertaken. Among these, 62 pts (M=37, F=25) had MM (1st-line=54, relapsed=8) and all received high-dose CY and G-CSF. Median age was 56 (37-75) yrs. ISS stage was I (n=34), II (n=16), and III (n=12). Pre-transplant induction consisted of VAD or VAD-like chemotherapy (n=26), bortezomib(bor)/dexamethasone (dex) (n=15), thalidomide (thal) /dex (n=10), bor/thal/dex (n=10), and 1 received bor/lenalidomide/dex. Fifty-six received fractionated high-dose CY (5g/m2 divided in 5 doses of 1g/m2 q 3 hrs) whereas 6 received CY 50 mg/kg for 2 doses. G-CSF was given at a fixed dose of 300 µg SQ q 12 hrs. Results All 62 (100%) pts achieved a circulating CD34 count ≥20/µl which is the cut-off level at our center to proceed with apheresis. The median peak peripheral blood CD34+ cell count was 111.5 (21-575) cells/μL. Success rate of stem-cell mobilization defined as collection of more than 2x106 CD34+ cells/kg was 100%. Median stem cell collection yield was 15.9x106 CD34+ cells/kg. Moreover, 61 (98.4%) pts and 46 (74%) pts collected >5x106 and >10x106 CD34+ cells/kg, respectively. Only 4 (6.4%) pts required 2 apheresis sessions. Conversely, 40 (64.5%) pts required hospitalization for febrile neutropenia (n=38) or transfusion support (n=2) for a median of 4 (1-8) days. No one required intensive level of care and all recovered. Also, 17 (27.4%) pts required blood transfusions and 16 (25.8%) required platelets transfusion. Autografting was successfully performed in all pts using high-dose melphalan with a median time from mobilization to the first transplant of 31 (16-156) days and median infused CD34+ cells of 7x106/kg (3.1-15.3). All pts achieved successful hematologic engraftment with a median time for neutrophil engraftment (ANC ≥500/µL) of 11 days and platelet engraftment (platelet ≥20000/microliter) of 12 days. Conclusion Fractionated high-dose CY and G-CSF is a highly effective chemo-mobilization strategy in MM in terms of successful rate of mobilization (100%), efficiency of stem cell collection (high yield), and timely hematologic engraftment (100%). However, the relatively high-rate of hospitalizations for febrile neutropenia requires an assessment of its cost-efficiency as compared to new mobilization strategies using G-CSF and preemptive plerixafor. Disclosures: No relevant conflicts of interest to declare.

Phase III Randomized Stem Cell Mobilization Trial Comparing Standard Vs Double-Dose G-CSF Vs Standard Doses of G-CSF Plus GM-CSF in Hard to Mobilize Patients Undergoing An Autologous Hematopoietic Stem Cell Transplant (HSCT).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3228-3228
Author(s):  
Elizabeth Berger ◽  
Christopher Seet ◽  
Mala Parthasarathy ◽  
Tulio Rodriguez ◽  
Scott E. Smith ◽  
...  
Keyword(s):  
Stem Cell ◽  
Standard Dose ◽  
Stem Cell Mobilization ◽  
Phase Iii ◽  
Control Group ◽  
High Dose ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Gm Csf ◽  
Cell Mobilization

Abstract Abstract 3228 Poster Board III-165 Introduction Using standard dose G-CSF (10 μg/kg) for stem cell mobilization, 25-40% of patients, deemed to be hard to mobilize based on prior therapy, will not collect sufficient HSC (> 2-2.5 × 106 CD34/kg) to proceed to a prompt autotransplant. Strategies to improve CD34/kg yields have included dose escalating G-CSF up to 30 μg/kg or combining G-CSF and GM-CSF. While dose escalated G-CSF is effective in increasing CD34 yields in normal donors as is the combination of G-CSF and GM-CSF, their comparative value in pre-treated patients has not been tested. To determine the value of these strategies, we performed a randomized comparison of high dose G-CSF (30 μg/kg as 2 doses 12 hours apart), to the combination of simultaneous single daily doses of G-CSF (10 μg/kg) plus GM-CSF (5 μg/kg), to a control group receiving G-CSF at an equivalent total dose of cytokine to the combination arm (15μg/kg) as a single dose. Patients and Methods Patients were eligible if heavily pre-treated, defined as: a minimum of 10 total cycles of combination chemotherapy and two prior regimens, or a total of 6 chemotherapy cycles if the patient also received RT to marrow bearing sites, platinum-based chemotherapy or 2 or more cycles of any BCNU or fludarabine containing regimen. Baseline WBC had to be > 3000/μl, ANC > 1500/μl and a platelets > 100,000/μl. Twelve liter aphereses began on day 5 of mobilization, and continued until ≥ 4 × 106 CD34/kg were collected or a maximum of 5 aphereses. Patients typically proceeded to transplant if they had ≥ 2.5 × 106 CD34/kg collected and were always re-mobilized if they collected < 2.0 × 106 CD34/kg. CD34 subsets (CD34+/CD33- and CD34+/CD38-) were also assessed for the 3 groups to determine if more primitive HSC were mobilized by the 2 novel strategies. The sample size was calculated based as follows: 60% of the control group would collect 2.5 × 106 CD34/kg and this would rise to 90% in one or both study arms. The detection of such differences with a power of 80% and a 2-sided alpha level of 0.025 required a total sample of 120 patients. Results A total of 120 patients were randomized; 119 were eligible. Patient demographics, shown in the Table, were matched among the three groups: The % of patients collecting ≥2.5 × 106 CD34/kg was: standard G: 60%, high dose G: 57% (p = 1.0), G + GM: 41% (p = 0.1). Median CD34 collected in first mobilization were, 3.6 × 106/kg, 3.0 × 106/kg (p = 0.22) and 2.0 × 106/kg (p = 0.05) respectively in a median of 4, 4, and 5 aphereses (p = NS). Re-mobilization rates: standard G; 37.5%, high dose G: 35%; G + GM: 50% (p = NS). Total median CD34 collected from first and any second mobilizations were: standard G: 4.8 × 106/kg, high dose G: 3.9 × 106/kg, and G + GM: 3.5 × 106/kg. One patient in the standard G arm and 3 in high dose G did not proceed to transplant due to poor initial mobilization and progression in 2, and one each for progression or poor mobilization alone. There were no significant differences in median engraftment times: for ANC, 10, 11 and 15 days respectively for the standard G-, high dose G- and G + GM arms and for platelets, 11, 13 and 14 days respectively. The overall survivals @ the median f/u time of 37 months were 59.8%, 61.8% and 48.1% respectively (p = 0.272) for the three groups. The % primitive HSC (CD34+/CD33- and CD34+/CD38-) from the first mobilization were identical in the 3 patient groups. Conclusions We found no advantage to dose escalated G-CSF nor to the combination of G-CSF and GM-CSF to mobilize HSC for autotransplantation in heavily pre-treated patients. We also did not find higher numbers of more primitive CD34 subsets mobilized by these newer strategies. Alternative approaches, e.g. the combination of plerixifor + standard dose G-CSF (Stiff et al: BBMT; 15:249-56, 2009) would appear to be the preferred method of initial HSC mobilization for heavily pre-treated patients. Disclosures Stiff: Genzyme: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Plerixafor and G-CSF For Autologous Stem Cell Mobilization In AL Amyloidosis: A Single Center Experience

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4516-4516
Author(s):  
Esha Kaul ◽  
Gunjan L Shah ◽  
Chakra P Chaulagain ◽  
Raymond L. Comenzo
Keyword(s):  
Stem Cell ◽  
Research Funding ◽  
Median Number ◽  
Initial Therapy ◽  
Stem Cell Mobilization ◽  
High Dose ◽  
Al Amyloidosis ◽  
Cell Transplant ◽  
Cd34 Cells ◽  
Cell Mobilization

Background Risk-adapted melphalan and stem cell transplant (SCT) is standard initial therapy for a minority of patients with systemic AL amyloidosis (Blood 2013;121: 5124; Blood 2011;118: 4298). Stem cell mobilization is often accomplished with high dose G-CSF (16μg/kg/d) (Blood 2011;118:4346). In the current era with effective new agents such as bortezomib, many AL patients are receiving initial therapy and achieving profound rapid cytoreduction with organ improvement (Blood 2012;119:4391; Blood 2011;118:86). But not all patients respond and in some cases the duration of response is limited. In addition, the use of SCT for consolidation after an initial response, although reasonable, has not been systematically evaluated. Whether SCT is employed as consolidation or as a second- or third-line option, the efficacy and tolerance of mobilization become important issues. Because AL patients have organ involvement limiting chemotherapy-based mobilization options, we decided to explore the option of Plerixafor and G-CSF for stem cell mobilization, based on the phase III experience in MM (Blood 2009;113:5720). We now report the first experience with this mobilization approach in AL. Patients and Methods Patients were evaluated and diagnosed by standard criteria including, in all cases, tissue biopsies showing amyloidosis. They were mobilized and collected between 4/16/12 and 6/19/13 with G-CSF 10μg/kg/d subcutaneously (SC) for 5 days (continued through collection process) and Plerixafor adjusted for renal function starting on day 4 and continuing until collection was completed. Results We report on 10 patients whose median age at mobilization was 58 years (range 46-72), 60% of whom were men. Median number of organs involved was 2 (range 1-3). Heart and kidneys were the most frequently involved organs (7 patients in each group). Median time from diagnosis to mobilization was 9 months (range 2-123). Eight patients had received prior bortezomib-based therapy. The median number of cycles was 3 (range 0-6). One had received a prior MEL 140 transplant 10 years prior and had relapsed, and 2 were treatment naïve, one of whom was 1 year status post orthotopic heart transplant. At the time of mobilization, 3 patients had non-responsive hematologic disease, 3 had achieved PR, 1 VGPR and 1 had achieved CR. Five patients had a creatinine ≥ 1.5 mg/dL including 2 patients on hemodialysis. The target cell dose was 10x106CD34/kg for all but one patient (with previous history of transplantation). The median number of collections was 2 (range 2-3). On day one, the median number of CD34+ cells collected per kg was 3.6 x106 (0.4-6x106) and on day two 6.4 x106 (2.7-19x106). The median total CD34+ cells collected per kg was 12.5x106 (5-18x106). Two patients had grade 1 bleeding from the catheter site during apheresis and one patient had dyspnea with suspected fluid overload which responded to a single dose of intravenous furosemide. There were no significant toxicities observed with Plerixafor in mobilization. All patients went on to receive high dose chemotherapy with melphalan followed by autologous stem cell transplant. The median length of hospital stay was 25 days (18-32). The median stem cell dose infused was 7.6x106CD34/kg and median days to ANC > 500 was 11 (10-22), to platelets > 20K untransfused 22 (15-44) and to lymphocytes > 500/μl 14.5 (11-25). One patient who had VOD and persistent thrombocytopenia was given the remainder of his stem cells on day +31 with full recovery and normalization of the blood counts by day +65. Conclusions In the era of more effective initial therapies, an era in which AL patients are living longer, many with moderate organ damage, mobilization with Plerixafor and G-CSF was well tolerated and made it possible to collect ample numbers of CD34+ cells with limited leukaphereses in previously treated patients and in those with advanced renal failure. This approach not only allowed the collection of sufficient CD34+ cells for optimal immediate stem cell dosing but also permitted the cryopreservation of aliquots for post-SCT boost and potentially for future cell-based therapies. Disclosures: Comenzo: Millenium: Membership on an entity’s Board of Directors or advisory committees, Research Funding; Prothena: Research Funding; Teva: Research Funding.

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

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5823-5823
Author(s):  
Ahmad Antar ◽  
Zaher Otrock ◽  
Mohamed Kharfan-Dabaja ◽  
Hussein Abou Ghaddara ◽  
Nabila Kreidieh ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Peripheral Blood ◽  
Stem Cell Mobilization ◽  
Cell Yield ◽  
Fixed Dose ◽  
High Dose ◽  
Peripheral Blood Cd34 ◽  
Cd34 Cells ◽  
Cell Mobilization

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

Sign in / Sign up

Export Citation Format

Share Document