Successful Stem Cell Mobilization with High-Dose Cytarabine Plus G-CSF after Lenalidomide Therapy for Multiple Myeloma - a Series of Four Cases

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5831-5831
Author(s):  
Jun Ishiko ◽  
Kazuaki Sato ◽  
Ruri Kato ◽  
Manabu Kawakami ◽  
Masashi Nakagawa ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Induction Therapy ◽  
Negative Impact ◽  
Stem Cell Mobilization ◽  
High Dose ◽  
Cell Harvesting ◽  
Cd34 Cells ◽  
High Dose Cytarabine ◽  
Cell Mobilization

Abstract Of late years, newly developed agents, such as bortezomib, lenalidomide, thalidomide, are widely used for treatment against multiple myeloma. After induction therapy, candidates for autologous stem cell transplantation are supposed to be followed by stem cell harvesting. There are several reports showing lenalidomide has a negative impact on stem cell mobilization. This opinion tends to let us refrain from using lenalidomide on the myeloma patients who are eligible for transplantation, even lenalidomide is expected promising. We experienced a series of three clinical cases presenting that stem cells were poorly mobilized with cyclophosphamide (CY) plus G-CSF after lenalidomide treatment, but sequential stem cell mobilization was incredibly improved with high-dose cytarabine plus G-CSF. One additional case who was treated with lenalidomide also presented successful stem cell mobilization with high-dose cytarabine plus G-CSF. Here we show all four cases in detail. Case 1: 66 years old male, symptomatic myeloma after smoldering period. After three course of bortezomib induction, the response was insufficient. Sequentially he was treated with lenalidomide (25mg/day, every day for three weeks with one week rest period) and dexamethasone (Dex) (40mg/day, weekly) for two courses, and finally achieved Partial response (PR). First peripheral blood stem cell harvesting was attempted with high-dose CY (2.0 g/m2, day1-2) + lenograstim (5mg/kg daily, on days 7 until leukapheresis), but mobilization was unsuccessful so harvesting was not performed. For subsequent mobilization, high-dose cytarabine was administered at a dose of 2.0 g/m2 twice daily (day1-2) + lenograstim. Second mobilization was markedly improved, and finally 33.0 x 106/kg CD34+ cells were obtained. Case 2: 63 years old male, symptomatic myeloma, IgG type. This patient was treated with bortezomib, CY and Dex but resulted in disease progression. As an alternative therapy, lenalidomide (10mg/day, daily for three weeks with one week rest) and Dex (40mg, weekly) were used for three cycles. The dose of lenalidomide was reduced due to renal dysfunction. PR was obtained, then first harvesting was attempted with high-dose CY + lenograstim, as case 1, and 0.088 x 106/kg of CD34+ cells were collected, which was not sufficient for transplantation. Second mobilization was performed with high-dose cytarabine as case 1, and consequently we could obtain 60.1 x 106/kg of CD34+ cells; the yield was dramatically improved. Case 3: 41 years old female, symptomatic myeloma after one year course of smoldering myeloma. As an induction therapy, bortezomib, CY and Dex were selected, but finally she could not achieved PR after three cycles. We gave up bortezomib-based induction, and then lenalidomide (15-25 mg on day1-21 with 1 week rest) and Dex (40 mg, weekly) were administrated for five courses, followed by PR. As previous two cases, the first peripheral stem cell collection was initiated with high-dose CY + lenograstim, and it was not sufficient (0.059 x 106/kg of CD34+ cells). And the second mobilization with high-dose cytarabine with lenograstim recovered the yield of stem cell up to 6.90 x 106/kg. Case 4: 63 years old male, symptomatic myeloma. He was treated with bortezomib, Dex with/without CY, but this regimen was not very effectual, and CY caused elevation of aminotransferase (CTCAE grade 3). Then lenalidomide (10-15 mg on day 1-21) and Dex (40 mg, weekly) were administrated for four courses, and the patient achieved PR. Due to the adverse effect of liver dysfunction, we could not use high-dose CY for mobilization. For this case, high-dose cytarabine was selected for first mobilization, and it was very successful, 50.2 x 106/kg of CD34+ cells were harvested. The yields of PBSC from all four cases are summarized on Table 1. These four cases suggest mobilization with high-dose cytarabine could be an alternative option for poor mobilizer of myeloma patient treated with lenalidomide-based induction. This fact may enable us to choose lenalidomide, not only bortezomib, for induction even for transplant-eligible cases. Figure 1 Figure 1. Disclosures Ishiko: Celgene: Honoraria.

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.

Bortezomib Given in Sequence with Anthracycline and Thalidomide-Containing Regimens Does Not Adversely Affect Stem Cell Mobilization and Engraftment in Patients with Multiple Myeloma Undergoing Autologous Hematopoietic Stem Cell Transplantation.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 541-541
Author(s):  
Geoffrey L. Uy ◽  
Nicholas M. Fisher ◽  
Steven M. Devine ◽  
Hanna J. Khoury ◽  
Douglas R. Adkins ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Peripheral Blood ◽  
Stem Cell Mobilization ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Cd34 Cells ◽  
Cell Mobilization ◽  
High Dose Melphalan

Abstract Bortezomib (VELCADE®) is a selective inhibitor of the 26S proteasome proven to be safe and effective in the treatment of relapsed or refractory multiple myeloma (MM). While high-dose chemotherapy with autologous hematopoietic stem cell transplant (AHSCT) remains the standard of care, there is considerable interest in incorporating bortezomib into the initial treatment of MM. However, the role of bortezomib in frontline therapy for MM will depend in part on its effects on subsequent stem cell mobilization and engraftment. We conducted a pilot study of bortezomib administered pretransplant followed by high-dose melphalan with AHSCT. Two cycles of bortezomib 1.3 mg/m2 were administered on days 1, 4, 8, and 11 of a 21-day treatment cycle. One week after the last dose of bortezomib, stem cell mobilization was initiated by administering filgrastim 10 mcg/kg/day subcutaneously on consecutive days until stem cell harvest was completed. Stem cell collection began on day 5 of filgrastim via large volume apheresis (20 L/day) performed daily until a minimum of 2.5 x 106 CD34+ cells/kg were collected. Patients were subsequently admitted to the hospital for high-dose melphalan 100 mg/m2/day x 2 days followed by reinfusion of peripheral blood stem cells 48 hours later. Sargramostim 250 mcg/m2/day subcutaneously was administered starting day +1 post-transplant and continued until the absolute neutrophil count (ANC) ≥ 1,500/mm3 for 2 consecutive days. To date, 23 of a planned 40 patients have been enrolled in this study with 19 patients having completed their initial therapy with bortezomib followed by AHSCT. Patient population consists of 16 male and 7 female patients with the median age at diagnosis of 58 years (range 38–68). Myeloma characteristics at diagnosis were as follows (number of patients): IgG (16), IgA (7) with stage II (9) or stage III (14) disease. Prior to receiving bortezomib, 11 patients were treated with VAD (vincristine, Adriamycin and dexamethasone) or DVd (Doxil, vincristine and dexamethasone), 5 patients with thalidomide and 5 patients with both. Two patients did not receive any prior chemotherapy. All patients successfully achieved the target of 2.5 x 106 CD34+ cells/kg in either one (15/19 patients) or two (4/19 patients) collections with the first apheresis product containing a mean of 5.79 x 106 CD34+ cells/kg. Analysis of peripheral blood by flow cytometry demonstrated no significant differences in lymphocyte subsets before and after treatment with bortezomib. Following AHSCT, all patients successfully engrafted with a median time to neutrophil engraftment (ANC ≥ 500/mm3) of 11 days (range 9–14 days). Platelet engraftment (time to platelet count ≥ 20,000/mm3 sustained for 7 days without transfusion) occurred at a median of 12 days (range 9–30 days). Eleven patients were evaluable for response at 100 days post-transplant. Compared to pre-bortezomib paraprotein levels, 3 patients achieved a CR or near CR, 7 maintained a PR while 1 patient developed PD. We conclude that pretransplant treatment with 2 cycles of bortezomib does not adversely affect stem cell yield or time to engraftment in patients with MM undergoing AHSCT. Updated results and detailed analysis will be available at the time of presentation.

Combination High-Dose Cyclophosphamide and Bortezomib Is Safe and Effective for Stem Cell Harvesting in Chemotherapy Refractory Multiple Myeloma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5459-5459 ◽  
Author(s):  
Miriam Katzman ◽  
Theresa George ◽  
Heather Doell ◽  
Patricia Danyluk ◽  
Sheri Briggs ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Stem Cell ◽  
Combination Chemotherapy ◽  
Plasma Cells ◽  
Stem Cell Mobilization ◽  
High Dose ◽  
Cell Harvesting ◽  
Cell Mobilization ◽  
Cell Harvest

Abstract Introduction: High-dose melphalan and autologous stem cell transplantation is the accepted therapy for most patients with multiple myeloma (MM) following steroid-based induction therapy. In a significant proportion of patients, however, the disease is refractory to standard induction. The use of dose-intense combination chemotherapy, such as D-PACE (dexamethasone, doxorubicin, cyclophosphamide, and cisplatin), may affect the ability to harvest an adequate number of hematopoeitic stem cells prior to transplantation. In addition, in those patients not achieving adequate cytoreduction despite combination chemotherapy, there is a theoretical risk of stem cell product contamination by malignant plasma cells. Bortezomib is a therapeutic agent with a novel mechanism of action, which in preliminary studies appears to be synergistic to alkylating agents and does not appear to affect stem cell yield. We piloted the addition of bortezomib to high-dose cyclophosphamide during stem cell harvesting in a series of patients failing to achieve an adequate response to D-PACE salvage. Patients and Methods: Between 2002 and 2006, fifteen MM patients refractory to standard dexamethasone-based induction therapy received ≥ 2 cycles of D-PACE prior to proceeding to autologous stem cell harvest and transplantation. 7/15 patients achieved adequate cytoreduction and proceeded to high-dose cyclophosphamide (3 g/m2) and filgrastim plus ancestim stimulation for stem cell mobilization. However, 8 patients in this cohort did not achieve adequate disease cytoreduction following D-PACE. Therefore, bortezomib was added to the mobilization regimen on days 1, 4, 8, and 11, in addition to high-dose cyclophosphamide given on day 11. Identical growth factor stimulation was provided. Response assessment included days to stem cell harvest, number of CD34 cells harvested, plasma cells in the product, disease response, and hematologic parameters. Results: Pre-treatment toxicities from D-PACE were similar in both groups. The addition of bortezomib to cyclophosphamide during stem cell mobilization did not lead to increased symptomatic toxicity. Grade 3/4 thrombocytopenia occurred in 5/8 patients receiving combination bortezomib/cyclophosphamide. No episodes of significant bleeding, peripheral neuropathy, or skin rash were noted. The average CD34-positive stem cell harvest in both groups was >5.0 × 106/kg. Time to stem cell harvesting was not significantly different between the groups. Flow cytometric examination of the harvested product from the bortezomib/cyclophosphamide group consistently demonstrated <2% cells bearing plasma cell markers. One patient in each group failed to mobilize sufficient stem cells. Bone marrow plasmacyte counts following combination therapy and harvesting decreased in all assessed patients. Time to engraftment was similar in both groups. Post-transplant disease control and survival remains to be assessed, as some patients in the combination group have only recently undergone transplantation. Conclusion: The addition of bortezomib to high-dose cyclophosphamide during stem cell mobilization does not increase toxicity or decrease stem cell harvest yield or quality, and appears to achieve adequate disease reduction in patients otherwise refractory to combination chemotherapy. This may result in improved relapse-free survival in patients with refractory MM.

Cyclophosphamide Overcomes the Suppressive Effect of LenalidomideTherapy on Stem Cell Collection in Preparation for Autologous Stem Cell Transplantation for Multiple Myeloma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3024-3024
Author(s):  
Tomer Mark ◽  
David Jayabalan ◽  
Roger N. Pearse ◽  
Jessica Stern ◽  
Jessica Furst ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Induction Therapy ◽  
Stem Cell Mobilization ◽  
Cd34 Cells ◽  
Cell Mobilization ◽  
Stem Cell Collection

Abstract Multiple Myeloma (MM) therapy has evolved over recent years to include powerful new therapeutic agents. The goal for most patients with MM, however, still remains high-dose chemotherapy followed by autologous stem cell transplantations as this procedure has been proven to have a therapeutic benefit. Therefore, the selection of an induction therapy must take into consideration the potential impact on the ability to collect enough stem cells for future transplantation. Recent studies have discussed difficulty in collecting stem cells in patients receiving lenalidomide-based induction therapy using filgastrim (G-CSF) in preparation for autologous stem cell transplantation in MM. It also has been recommended that the duration of lenalidomide induction therapy be limited to 4–6 cycles, since longer treatment time can hinder collection yields. We sought to determine if the addition of cyclophosphamide (CTX) to G-CSF as a mobilization regimen could rescue the ability to collect adequate stem cells for at least two autologous stem cell transplants for patients who had induction therapy with the BiRD (Biaxin® [clarithromycin]/Revlimid® [lenalidomide]/dexamethasone) regimen. BiRD therapy is as follows for each 28-day cycle: Clarithromycin 500mg po BID for days 1–28, Lenalidomide 25mg po daily for days 1–21, and Dexamethasone 40mg po weekly on days 1, 8, 15, and 21. All patients had either Stage II or III MM by Salmon-Durie criteria and were treatment naïve. Patients were advised to undergo stem cell collection after either maximum disease response or disease plateau had been achieved. Prior to stem cell mobilization, BiRD therapy was held for a minimum of 14 days. Stem cell collection was performed after either G-CSF alone at a dose 10 mcg/kg/day for 5–10 consecutive days until a total of 10 × 106/kg CD34+ stem cells had been collected or with the addition of cyclophosphamide (CTX) at a dose of 3g/m2 once prior to the initiation of G-CSF therapy. A total of 28 patients underwent stem cell collection. Stem cell mobilization was attempted with G-CSF alone in 9 instances and with CTX+G-CSF in 20 instances (1 patient underwent mobilization with both G-CSF alone and CTX+G-CSF). In comparison to the G-CSF monotherapy, CTX+G-CSF yielded a significantly greater stem cell collection (mean CD34+ cells collected: 3.78 × 106/kg vs. 32.33 × 106/kg, P < 0.0001). Only 33% of patients who attempted stem cell mobilization with G-CSF alone obtained sufficient CD34+ cell yield vs. 100% of the patients mobilized with CTX+G-CSF (P < 0.0001). The extent of BiRD therapy prior to stem cell mobilization ranged from 2–27 cycles. The number of cycles of BiRD did not significantly impact the success rate of stem cell collection (P = 0.14). In conclusion, the patients mobilized with CTX+G-CSF had a higher number of CD34+ cells collected and were all able collect enough stem cells for two autologous transplants. There was no association with the duration of BiRD therapy and successful CD34+ cell collection. We therefore recommend continuing lenalidomide-based induction therapy until desired tumor reduction goal is achieved and using the CTX in addition to G-CSF to ensure successful stem cell harvest prior to autologous transplantation.

scholarly journals Evaluation of Stem Cell Mobilization in Patients with Multiple Myeloma after Lenalidomide-Based Induction Chemotherapy within the GMMG-HD6 Trial

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3373-3373 ◽  
Author(s):  
Patrick Wuchter ◽  
Uta Bertsch ◽  
Hans-Juergen Salwender ◽  
Markus Munder ◽  
Mathias Haenel ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Board Of Directors ◽  
Induction Therapy ◽  
Research Funding ◽  
Stem Cell Mobilization ◽  
Phase Iii ◽  
Advisory Committees ◽  
Cd34 Cells ◽  
Cell Mobilization

Abstract Introduction: The German-Speaking Myeloma Multicenter Group (GMMG) has initiated a randomized multicenter phase III trial on the effect of elotuzumab in VRD (bortezomib, lenalidomide, dexamethasone) induction/consolidation and lenalidomide maintenance in patients with newly diagnosed multiple myeloma (GMMG-HD6 trial, NCT02495922). The study compares four cycles induction therapy with VRD vs. VRD + elotuzumab, followed by standard intensification (i.e. mobilization and stem cell transplantation), two cycles consolidation with VRD/VRD + elotuzumab and lenalidomide maintenance +/- elotuzumab. The primary endpoint is determination of the best of four treatment strategies regarding progression-free survival. Here we present a first analysis of stem cell mobilization within this study. Patients and Methods: We performed a retrospective analysis of collection data on all patients who underwent peripheral blood stem cell (PBSC) collection between trial initiation in June 2015 and June 2016. Only patients with completely available datasets in respect of mobilization were considered (n=111). The vast majority of 99 patients (89%) received chemomobilization with CAD (cyclophosphamide, adriamycin, dexamethasone) followed by 5-10 µg G-CSF /kg body weight (bw) /d (starting day +9 until completion of PBSC collection), while in one case (1%) dexamethasone was omitted and in 10 cases (9%) cyclophosphamide mono was administered. One patient underwent steady-state mobilization with G-CSF only (10µg /kg bw /d). 55/111 patients received VRD (50%), whereas the remaining patients received VRD + elotuzumab. According to the recommendations of the study group, PBSCs for three stem cell transplants were to be collected. One transplant ideally consisted of ≥2.5 x10^6 CD34+ cells /kg bw, but in the event of poor mobilization as low as ≥2.0 x10^6 CD34+ cells /kg bw would be considered acceptable. Results: The median number of collected CD34+ cells was 10.4 x10^6 /kg bw (range 2.88 to 23.01 x10^6 /kg bw). Overall, 92 patients (83%) collected ≥7.5 x10^6 CD34+ cells /kg bw and another 12 patients (11%) collected between 6.0 and 7.5 x10^6 CD34+ cells /kg bw, resulting in three transplants, respectively. Only 7 patients (6%) collected below 6.0 x10^6 CD34+ cells /kg bw; 5 of them had been treated in the VRD-arm without elotuzumab. Due to insufficient PBSC mobilization after conventional treatment, 14 patients (13%) received a rescue mobilization with plerixafor, from which 12 patients collected ≥6.0 x10^6 CD34+ cells /kg bw. Overall, 7 serious adverse events (SAEs) occurred during mobilization phase, 4 of them in the study arm with elotuzumab. Conclusions: Cyclophosphamide-based chemomobilization after induction therapy with VRD is feasible. Efficient PBSC collection of ≥6.0 x10^6 CD34+ cells /kg bw could be performed in 104 of 111 patients (94%), with a low incidence of SAEs. The need for rescue mobilization was not higher than that of comparable previous GMMG treatment protocols. The addition of elotuzumab during induction phase did not impede PBSC collection. Disclosures Wuchter: Sanofi-Aventis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Hexal: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Bertsch:Janssen: Research Funding; Celgene: Research Funding; Chugai: Research Funding. Munder:Janssen: Honoraria; Takeda: Honoraria; Amgen: Honoraria; Bristol Myers Squibb: Honoraria. Fenk:Jansen: Honoraria, Other: travel support; Celgene: Honoraria, Other: travel support, Research Funding. Hillengass:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria; Celgene: Honoraria; BMS: Honoraria; Novartis: Research Funding; Sanofi: Research Funding. Raab:Novartis: Consultancy, Research Funding; BMS: Consultancy; Celgene: Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Ho:Sanofi-Aventis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Scheid:Medac: Other: Travel, accomodations or expenses; Baxalta: Honoraria; Amgen: Consultancy; Novartis: Consultancy, Honoraria, Other: Travel, accomodations or expenses; Janssen: Consultancy, Honoraria; Celgene: Other: Travel, accomodations or expenses; BMS: Consultancy, Honoraria. Weisel:Onyx: Consultancy; Amgen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Novartis: Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria. Goldschmidt:Takeda: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Chugai: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Millennium: Membership on an entity's Board of Directors or advisory committees, Research Funding; Onyx: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees.

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.

The effect of induction therapy with novel agents on stem cell mobilization in multiple myeloma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8102-8102 ◽  
Author(s):  
A. Mazumder ◽  
S. Jagannath ◽  
D. Vesole
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Bone Marrow ◽  
Stem Cell ◽  
Induction Therapy ◽  
Stem Cell Mobilization ◽  
Stem Cell Markers ◽  
Number Of Patients ◽  
Cd34 Cells ◽  
Cell Mobilization

8102 Background: Thalidomide or bortezomib combined with dexamethasone (TD or BD respectively) are now being increasingly used as induction regimens for newly diagnosed multiple myeloma. There are conflicting reports on the effects of T on stem cell mobilization. Since we have used both these regimens at our center, we performed a retrospective analysis of stem cell mobilization after induction therapy with either TD (n = 22) or BD (n = 18). Methods: The patients were balanced with respect to initial Durie-Salmon stage, median number of cycles of induction therapy prior to collection, response to induction therapy, bone marrow cellularity and involvement, and time from end of therapy to collection. All patients were mobilized with G-CSF 10mcg/kg and collected in a large volume pheresis, with a goal of at least 6x10(6) CD34+ cells/kg (for tandem transplant). Results: To achieve our stem cell goal, the number of patients who required 3 or more phereses in the TD group was 17/22 whereas it was only 4/18 in the BD group. (p<0.005). 3/3 patients who had received lenalidomide also required 3 or more phereses. Also, the number of CD34+ cells/kg obtained in the TD group was less–mean of 2.8x10(6) per pheresis, as compared to a mean of 5.2x10(6) per pheresis in the BD group (p<0.01). Time to neutrophil engraftment was similar in both groups. However in the TD group there was a 1 day delay in platelets > 20,000/ul (p<0.05). Conclusions: Thus, thalidomide induction led to a lower yield of stem cells when compared to bortezomib. Differences in stem cell markers are being investigated. This may become especially important when limiting numbers of stem cells are available from elderly patients, those with prior radiation or bulk disease and when used for in vitro manipulation. It is possible that agents such as bortezomib may alter the bone marrow microenviroment differently from imids such as thalidomide. No significant financial relationships to disclose.

Clinical Impact and Resource Utilization After Stem Cell Mobilization Failure in Patients with Multiple Myeloma and Lymphoma.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2142-2142
Author(s):  
Morie A Gertz ◽  
Robert Wolf ◽  
Ivana N. Micallef ◽  
Dennis A. Gastineau
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Growth Factors ◽  
Hodgkin Lymphoma ◽  
Resource Utilization ◽  
Stem Cell Mobilization ◽  
Hodgkin Disease ◽  
Non Hodgkin Lymphoma ◽  
Cd34 Cells ◽  
Cell Mobilization

Abstract Abstract 2142 Poster Board II-119 High-dose chemotherapy in conjunction with autologous SCT is the preferred treatment of relapsed Hodgkin disease and non-Hodgkin lymphoma and newly diagnosed multiple myeloma. Failure to achieve optimal stem cell mobilization results in multiple subsequent attempts, which consumes large amounts of growth factors and potentially requires antibiotics and transfusions. We retrospectively reviewed the natural history of stem cell mobilization attempts at our institution from 2001 through 2007 to determine the frequency of suboptimal mobilization in patients with hematologic malignancy undergoing autologous transplant and analyzed the subsequent resource utilization in patients with initially failed attempts. Of 1,775 patients undergoing mobilization during the study period, stem cell collection (defined by the number of CD34+ cells/kg) was “ optimal” (≥5×106) in 53%, “low” (≥2 to 5×106) in 25%,“ poor” (<2×106) in 10%, and “failed” (<10 CD34+ cells/mL) in 12%. In the 47% of collections that were less than optimal, increased resource consumption included increased use of growth factors and antibiotics, subsequent chemotherapy mobilization, increased transfusional support, more apheresis procedures, and more frequent hospitalization. Other costs often omitted include the need for hospitalization, which was seen in 5% to 11% of the patients in our study. Parenteral antibiotics were needed when fever developed in 7% of patients with Hodgkin disease, 4% with non-Hodgkin lymphoma, and 24% with multiple myeloma who underwent mobilization using a chemotherapy pulse. When stem cell mobilization was not immediately optimal, subsequent attempts to mobilize failed completely in 3 of 42 patients (7%) with Hodgkin disease (3% of the original Hodgkin disease cohort), 56 of 157 (36%) with multiple myeloma (6% of the original myeloma cohort), and 50 of 328 (15%) with non-Hodgkin lymphoma (7% of the original non-Hodgkin lymphoma cohort). These usually unappreciated costs of stem cell mobilization failure highlight the need for more effective mobilization strategies. Disclosures: Gertz: genzyme: Research Funding.

High Number of Successful Mobilizations Associated with the Use of Plerixafor and Colony Stimulating Factors In Patients with Multiple Myeloma (MM) and Lymphoma Treated at Memorial Sloan-Kettering Cancer Center

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2263-2263
Author(s):  
Nelly G. Adel ◽  
Mathew Sherry ◽  
Stephen J. Harnicar ◽  
Emily Mccullagh ◽  
Heather Landau ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Adult Patients ◽  
Stem Cell Mobilization ◽  
Cancer Center ◽  
Published Data ◽  
First Line ◽  
Colony Stimulating Factors ◽  
Cd34 Cells ◽  
Cell Mobilization

Abstract Abstract 2263 Background: Autologous stem cell transplantation (ASCT) remains the only curative option for many lymphoma patients and it is an integral component of treatment for patients with multiple myeloma (MM). Stem cell mobilization has most commonly been performed using either chemotherapy and colony-stimulating factors or colony stimulating factors alone. This approach was challenged by the inability to collect enough CD 34 cell count to perform an ASCT. Plerixafor (Mozobil ®) previously known as AMD3100, a selective antagonist of CXCR4, has recently been approved for ASCT mobilization in combination with granulocyte- colony stimulating factor (G-CSF) for both multiple myeloma and lymphoma patients and is effective for patients who failed to mobilize enough CD34 cells with other modalities. Patients and Methods: This retrospective study examines all adult patients with MM and lymphoma who received plerixafor as a mobilization agent for ASCT at Memorial Sloan- Kettering Cancer Center between January 1st, 2009 and August 1st, 2010. Patient's information was obtained from the pharmacy data base and electronic medical records. Data included demographics, diagnosis, first line mobilization regimen, second and third line regimens, doses of plerixafor received, number of pheresis sessions and CD34 cells per kg collected per each session. The primary objective was to determine how many patients failed stem cell collection following mobilization at our center. Results: Fifty-six adult patients with lymphoma (N=23) and MM (N=33) were identified. Patients were excluded if they were treated for a pediatric malignancy or an alternate diagnosis. The average number of pheresis and CD34 cells/kg collected in each group are shown Table 1. Forty-three percent (10/23) patients with lymphoma received plerixafor and G-CSF as the first line option for mobilization and 57% (13/23) received plerixafor and G-CSF after failing other regimens. A total of 5 (22%) patients with lymphoma failed collection following mobilization with plerixafor, 1 as a primary mobilization failure and 4 having failed other mobilization strategies. Thirty-nine percent (13/33) of patients with MM received plerixafor and G-CSF as the first line option for mobilization and 61% (20/33)after failing other regimens, including cyclophosphamide (N=15) and G-CSF alone (N=5). Among the patients mobilized with plerixafor, 6% (2/33) failed collection, 1 who received plerixafor and G-CSF for primary mobilization and only 1 after failing other regimens. Conclusion: In lymphoma and MM patients plerixafor in combination with G-CSF is effective for stem cell mobilization and in this study we report higher success rates than in previously published data. The few number of failures with plerixafor plus G-CSF given as a primary mobilization regimen, supports its use in this setting and is attractive considering that it can reduce patient's exposure to chemotherapy. Disclosures: Matasar: Genzyme Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees.

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