Bortezomib Does Not Impair Cytokine Induced Mobilization of Stem Cells Prior to Autologous Transplantation in Multiple Myeloma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2926-2926 ◽  
Author(s):  
Geoffrey L. Uy ◽  
Nicholas M. Fisher ◽  
Steven M. Devine ◽  
Michael H. Tomasson ◽  
John F. DiPersio ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Stem Cell ◽  
Induction Therapy ◽  
High Dose ◽  
Front Line ◽  
Post Transplant ◽  
Autologous Transplant ◽  
Cd34 Cells ◽  
Stem Cell Collection

Abstract Bortezomib (VELCADE®) is a selective inhibitor of the proteasome approved for the treatment of relapsed or refractory multiple myeloma (MM). Emerging evidence indicates that bortezomib is also effective alone or in combination with cytotoxic agents in the front-line treatment of myeloma. Given the superiority of high dose therapy with autologous transplant compared to conventional therapy in myeloma, the application of bortezomib to novel front-line therapies depends in part on its effects on subsequent stem cell mobilization and engraftment. Previous reports have demonstrated successful chemotherapy induced mobilization of stem cells following bortezomib. To determine the effects of bortezomib on cytokine mobilization and engraftment of stem cells, we conducted a study of bortezomib administered prior to high-dose melphalan with autologous stem cell transplant. Following induction therapy, 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 cells were mobilized with G-CSF 10 mcg/kg/day for 5 days and harvested by large volume apheresis (20 L/day) until a minimum of 2.5 x 106 CD34+ cells/kg were collected. Melphalan 100 mg/m2/day x 2 days was administered followed by reinfusion of peripheral blood stem cells 48 hours later. GM-CSF 250 mcg/m2/day was given post-transplant until the ANC ≥ 1,500/mm3 for 2 consecutive days. Forty patients were enrolled in this study with 37 continuing on to autologous transplant. Study population consists of 24 male and 16 female patients with the median age at enrollment of 56 years (range 38–69). Myeloma characteristics at diagnosis were as follows (number of patients): IgG (29), IgA (10), light chain only (1), with stage I (1), II (12), or stage III (27) disease. Prior to receiving bortezomib, 20 patients had been previously treated with an anthracycline containing regimen and 22 with thalidomide for induction therapy. Two patients did not receive any prior chemotherapy. Two patients did not proceed to stem cell harvest, one secondary to disease progression on bortezomib and the other because of a stroke suffered during G-CSF mobilization. Stem cell collection was successful in 37 of 38 patients with the first collection containing a median of 4.24 x 106 CD34+ cells/kg. The majority of patients (29) required a single pheresis session, 7 required two sessions, and 1 patient required 5 sessions. The only patient failing stem cell collection had received extensive radiation to the pelvis in addition to a prior history of breast cancer for which she received adjuvant chemotherapy. All transplanted patients successfully engrafted with a median time to neutrophil engraftment (ANC ≥ 500/mm3) of 11 days (range 9–14 days). Platelet engraftment (platelet count ≥ 20,000/mm3 sustained for 7 days without transfusion) occurred at a median of 11 days (range 9–31 days). In an intention-to-treat analysis at 100 days post-transplant, we observed a compete response (CR) in 6 patients (15%), a near CR in 10 patients (25%) with an additional 19 partial responses (48%) for an overall response rate of 88%. We conclude that pre-transplant treatment with 2 cycles of bortezomib following anthracycline or thalidomide containing chemotherapy does not adversely affect stem cell yield or time to engraftment and results in high CR / near CR rates.

A Comparison of Chemotherapy + G-CSF Versus Plerixafor (Mozobil®) + G-CSF for Stem Cell Mobilization In Patients with Multiple Myeloma Treated with Lenalidomide

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2258-2258
Author(s):  
Tomer M Mark ◽  
Adriana C Rossi ◽  
Roger N Pearse ◽  
Morton Coleman ◽  
David Bernstein ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Stem Cell ◽  
Board Of Directors ◽  
Research Funding ◽  
Cell Yield ◽  
High Dose ◽  
Advisory Committees ◽  
Cd34 Cells ◽  
Stem Cell Collection

Abstract Abstract 2258 Background: Prior use of lenalidomide beyond 6 cycles of therapy in the treatment of multiple myeloma (MM) has been shown to negatively impact stem cell yield, but this phenomenon can be overcome with the addition of high-dose cyclophosphamide to standard G-CSF mobilization. We hypothesized that the use of plerixafor (Mozobil®) would compare similarly to chemotherapy in rescuing the ability to collect stem cells in lenalidomide-treated myeloma. Methods: We performed a retrospective study comparing the efficacy of plerixafor + G-CSF mobilization (PG) to chemotherapy + G-CSF (CG) (either high-dose cyclophosphamide at 3g/m2 or DCEP [4-day infusional dexamethasone/ cyclophosphamide/ etoposide/cisplatin]) in 49 consecutive stem cell collection attempts in patients with MM exposed to prior lenalidomide. The primary endpoint was the ability to collect sufficient stem cells for at least two transplants (minimum 5×106 CD34+ cells/kg), comparing results in terms of total exposure to lenalidomide and time elapsed from lenalidomide exposure until the mobilization attempt. The secondary endpoint was number of apheresis days required to meet collection goal. Resilts: Twenty-four patients underwent PG mobilization and twenty-five with CG (21 with G-CSF + cyclophosphamide, 4 with G-CSF+DCEP). The two groups did not differ in terms of total amount of lenalidomide exposure: median number of lenalidomide cycles for patients mobilized with PG was 6.5 (range 1.2–86.6), vs. 6 (range 2–21.6), for patients mobilized with CG (P = 0.663). The median time between mobilization and last lenalidomide dose was also similar between the two groups: 57.5 (range 12–462) days for PG vs. 154 (range 27–805) days for CG (P = 0.101). There was an equivalent rate of successful collection of 100% for PG and 96% for CG, P = 0.322. One patient failed collection in the CG group due to emergent hospitalization for septic shock during a period of neutropenia; no patient collected with PG had a serious adverse event that interrupted the collection process. Stem cell yield did not differ between the two arms (13.9 vs. 18.8 × 106 million CD34+ cells/kg for PG vs. CG respectively, P = 0.083). Average time to collection goal was also equal, with a median of time of 1 day required in both groups, (range 1–2 days for PG, 1–5 days for CG, P = 0.073). There was no relationship between amount of lenalidomide exposure and stem cell yield with either PG (P = 0.243) or CG (P = 0.867). Conclusion: A plerixafor + G-CSF mobilization schedule is equivalent in efficacy to chemotherapy + G-CSF in obtaining adequate numbers of stem cells for two autologous stem cell transplants in patients with MM exposed to lenalidomide; however, PG may be a less toxic approach than chemomobilization. Number of lenalidomide cycles has no impact on chances of stem cell collection success using either method. Disclosures: Mark: Celgene Corp: Speakers Bureau; Millenium Corp: Speakers Bureau. Zafar: Celgene Corp: Speakers Bureau. Niesvizky: Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Millenium: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Onyx: Consultancy, Research Funding.

The Effect of Rituximab on Mobilization with AMD3100 Plus G-CSF in Patients with Relapsed or Refractory NHL or HD.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1912-1912
Author(s):  
Jonathan L. Kaufman ◽  
Amanda M. Cook ◽  
Christopher Flowers ◽  
Amelia A. Langston ◽  
Sagar Lonial ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Median Number ◽  
High Dose ◽  
High Dose Therapy ◽  
Hematopoietic Stem ◽  
Post Transplant ◽  
Dose Therapy ◽  
Cd34 Cells ◽  
Stem Cell Collection

Abstract The optimal therapy for patients with chemotherapy sensitive relapsed or refractory lymphoma is high dose therapy followed by autologous hematopoietic stem cell rescue. Rituximab (R) has been added to salvage regimens to increase response rate, thereby making more patients eligible for high dose therapy. However, when R is used prior to the salvage regimen, it has been associated with a delay in platelet engraftment (Hoerr et al, J Clin Oncol. 2004 Nov 15;22:4561–6). We have previously noted in a retrospective review of 117 patients with lymphoma treated with high dose therapy and autologous HSC transplant that concurrent treatment with R did not impact stem cell collection or post transplant engraftment (Kaufman et al, BBMT, February 2005, Sup 1, [11.2] 6). AMD3100 (plerixafor) is a CXCR4 inhibitor that, when used with G-CSF, more effectively mobilizes stem cells than G-CSF alone. In order to test the hypothesis that R does not negatively impact stem cell collection or post-transplant engraftment when AMD3100 is used with G-CSF, we performed a prospective trial of the use of AMD3100, G-CSF and R for patients with CD20 (+) relapsed chemosensitive lymphoma versus the use of AMD3100 and G-CSF for patients with CD20 (−) relapsed chemosensitive lymphoma. Patients were treated with 2 cycles of ICE ± R depending on CD20 status of the malignant cell. Patients who had a response proceeded to mobilization with AMD3100 and G-CSF for the CD20 (−) group (Arm A) or AMD3100, G-CSF, and four weekly doses of R at 375 mg/m2 (two doses prior to G-CSF and AMD3100, and two doses after) for the CD20 (+) group (Arm B). After collection, patients were treated with high dose therapy with targeted intravenous busulfan, etoposide and cyclophosphamide followed by autologous HSC transplantation. Patient demographics, mobilization characteristics, graft yield, engraftment data, and toxicity were assessed. 21 patients have been accrued. 11 in Arm A (10 Hodgkin Lymphoma {HL} and 1 with Peripheral T Cell Lymphoma) and 10 in Arm B (2 HL and 7 NHL, and 1 with a composite HL/NHL). The median number of days of collection was 2 for each arm. The median CD34 (+) collected was 4.64 * 106 CD34+ cells/kg in Arm A compared to 5.25 * 106 CD34+ cells/kg in Arm B (p=0.6) The median number of CD34(+)/CD38(−) was similar for both arms. As expected from in vivo B-cell depletion, the percentage of CD19 (+) cells in the product was decreased in Arm B compared to Arm A (2.24% vs. 0.09%, p<0.002). R treated patients did not experience increased serious adverse events. All patients in both arms had durable and equivalent neutrophil and platelet engraftment (Table 1). In conclusion, rituximab can be administered safely to patients when AMD3100 and G-CSF are used for collection of hematopoietic stem cells. Importantly, no negative impact on graft characteristics or engraftment was perceived. Further trials are planned. Table 1: Engraftment Arm A Arm B p value N 11 10 CD 20 status negative positive Median Day to Neutrophil Engraftment 12 11.5 0.39 Median Day to Platelet Engraftment 17 17 0.72 Median Day 100 Total WBC 4.0 3.5 0.55 Median Day 100 Platelet Count 179 178 0.77

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.

Transplantation of Peripheral Blood Stem Cells Mobilized by Chemotherapy and Single Dose Pegylated G-CSF in Patients with Multiple Myeloma: Equivalence of 6 mg and 12 mg Pegfilgrastim.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2868-2868 ◽  
Author(s):  
Ingmar Bruns ◽  
Ulrich Steidl ◽  
Christof Scheid ◽  
Kai Hübel ◽  
Roland Fenk ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Stem Cell ◽  
Single Dose ◽  
Peripheral Blood ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Cytotoxic Therapy ◽  
Cd 34 ◽  
Cd34 Cells

Abstract To date the most effective treatment for patients (pts) with multiple myeloma consists of conventional induction chemotherapy followed by either single or tandem high-dose chemotherapy and autologous blood stem cell transplantation. Collection of sufficient numbers of hematopoietic stem cells is essential for high-dose chemotherapy. Current regimens for stem cell mobilization are based on daily subcutaneous injections of human recombinant G-CSF starting shortly after cytotoxic therapy. Here we examined the use of polyethyenglycole (PEG)-conjugated G-CSF (pegfilgrastim) at two different doses in patients with stage II or III multiple myeloma. Patients received induction therapy with 2–4 cycles ID or VAD. Following cytotoxic therapy with cyclophosphamide (4g/m2) we administered either a single dose of 6 mg pegfilgrastim (n=10 pts; median age: 55 years), 12 mg pegfilgrastim (n=12 pts; median age: 51 years) or daily doses of 8,5 μg/kg unconjugated G-CSF (filgrastim) (n=12 pts; median age: 51 years). The growth factor was given on day 4 (range 2–5 days) in the “6 mg pegfilgrastim group”, on day 5 (range 2–7 days) in the “12 mg pegfilgrastim group” and on day 4 (range 3–6 days) in the “filgrastim group” after cyclophosphamide. Numbers of CD34+ cells were determined during leukocyte recovery and harvested by large volume apheresis using a cobe spectra blood cell separator. Pegfilgratim was associated with an earlier leukocyte recovery both at the 6mg dose (median 12 days, range 8–16 days) and the 12mg dose (median 12 days, range 7–16 days) as compared to filgrastim (median 14 days, range 11–15 days, p=0.04). Similarily, the peripheral blood CD34+ cell peak occurred earlier in patients who received pegfilgrastim (median 12 days, range 11–18 days versus median 15 days, range 12–18). On the other hand the peripheral blood CD 34+ peak did not differ significantly between the three groups (median 129/μl with 6 mg pegfilgrastim, range 30–433, median 78/μl with 12 mg pegfilgrastim, range 20– 1055 and median 111/μl with filgrastim, range 28–760, p=0.95). With a median of 1.0x10E7 CD34+ cells per kg (range 5.8x10E6-1.9x10E7) in the “6 mg pegfilgrastim group”, 7.4x10E6 CD34+ cells per kg (median, range 4.9x10E6- 3.8x10E7) in the “12 mg pegfilgrastim group” and 10.8x10E6 CD34+ cells per kg (median, range 5.0x10E6-8.7x10E7) in the “filgrastim group” there were no significant differences in the total number of harvested CD34+ cells. Following high-dose therapy with melphalan (200 mg/m2) and autografting leukocyte and platelet reconstitution was similar within all groups. In summary, a single dose of pegfilgrastim after high dose cyclophosphamide is capable of mobilizing a sufficient number of CD 34+ cells for succesful autografting and sustained hematological reconstitution in patients with multiple myeloma. No difference could be observed between 6 mg and 12 mg of pegfilgrastim. Our data provide the basis for randomized studies evaluating the optimal dose and timing of pegfilgrastim as well as long-term outcome in larger cohorts of patients.

Ex-Vivo Expanded Peripheral Blood Stem Cells (EVEC) Compared with Un Manipulated Peripheral Blood Stem Cells (PBSC) Autologous Transplantation for Multiple Myeloma: A Pair Match Analysis.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 502-502 ◽  
Author(s):  
Noel-Jean Milpied ◽  
Gerald Marit ◽  
Bernard Dazey ◽  
Jean-Michel Boiron ◽  
Zoran Ivanovic ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Peripheral Blood ◽  
Ex Vivo ◽  
High Dose ◽  
Peripheral Blood Stem Cells ◽  
Cd34 Cells ◽  
Blood Stem Cells

Abstract Abstract 502 Autologous stem cell transplantation with PBSC after high-dose chemotherapy remains standard therapy for patients with symptomatic Multiple Myeloma (MM). Strategies to minimize complications could significantly reduce the morbidity of that procedure. One possibility could be to shorten the duration of induced neutropenia through the injection of an ex-vivo expanded graft. Nineteen patients (pts) received EVEC after high-dose Melphalan (HDM) (200 mg/m2) as the only graft. The ex-vivo expanded procedure has been described elsewhere (Boiron et al. Transfusion 2006 and Ivanovic et al. Transfusion 2006). Briefly, thawed peripheral blood CD 34+ cells collected after G-CSF mobilisation and selected with immunomagnetic devices were incubated for 10 days in a serum free medium (Maco Biotech HP01) with Stem Cell Factor (Amgen), G-CSF (Amgen) and TPO (Amgen: 7 pts; Cellgenix:12 pts). The expanded cells were then thoroughly washed and injected 48h after the HDM injection. The ex-vivo expansion lead to a median fold of 5,4 for CD34+ cells (1,3-11,8); 118 for CD33+ (1-703880); 3386 for CD14+ (4-101075); 28,5 for CD13+ (10-703880) and 13 for CFUs (6-21). The median N° of CD34+ cells injected was 14×10e6/kg (5,3-48). The results of these transplants were compared to those achieved in 38 pts who received unmanipulated PBSC after HDM. Pts and controls were matched for age, sex, stage of the disease, first line chemotherapy ( VAD or VD) status of the disease at time of transplant, year of transplant, time between diagnosis and transplant, CD34+ mobilisation technique (HD cytoxan + G-CSF or G-CSF alone) and the median N° of total nucleated cells and of CD34+ collected. The results are summarized on the table: There was no secondary neutropenia in the patients who received EVEC. With a median FU of the entire cohort of 30 m, the median OS for pts who received their first transplant with EVEC and with PBSC is 69 m and not reached respectively (p=NS), the median PFS is 18 m and 27 m (p = NS) and the median time to progression is 14 m and 15 m (p=NS). Conclusion: EVEC is feasible, safe and reduce significantly the morbidity of autologous stem cell transplantation after HDM for multiple myeloma. Disclosures: Milpied: Amgen France: Honoraria.

No Influence of Previous Thalidomide Administration on Peripheral Blood Stem Cell Collection in Patients with Multiple Myeloma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4902-4902
Author(s):  
Iris Breitkreutz ◽  
Axel Benner ◽  
Friedrich W. Cremer ◽  
Doris Herrmann ◽  
Anthony D. Ho ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Total Dose ◽  
Induction Therapy ◽  
Peripheral Blood ◽  
Peripheral Blood Stem Cell ◽  
Blood Stem Cell ◽  
Cd34 Cells ◽  
To Receive ◽  
Stem Cell Collection

Abstract OBJECTIVES: In a joint study of the GMMG and HOVON groups, induction therapy with Thalidomide (Thal), doxorubicin and dexamethasone (TAD) is currently investigated in comparison with vincristin, doxorubicin and dexamethasone (VAD) followed by mobilisation therapy with cyclophosphamide, doxorubicin and dexamethasone (CAD) and peripheral blood stem cell collection (PBSC). Munshi et al. (Blood 1999, Abstract #2577) described a dampening of PBSC-mobilisation by Thal treatment. We therefore investigated a possible influence of PBSC after previous Thal administration. METHODS: Altogether, data on 112 patients were analyzed in terms of PBSC-mobilisation. 56 patients were randomized up-front to receive 3 cycles of TAD (Thal 400mg/d orally; doxorubicin 9mg/m2/d, 4 30-min. infusions, day 1–4; dexamethasone 480mg total dose orally). 56 patients received VAD (vincristin 0,4mg/d and doxorubicin 9mg/m2/d, 4 30-min. infusions, day 1–4.; dexamethasone 480mg total dose orally) followed by mobilisation with CAD (cyclophosphamide 1g/m2/d, 1h infusion, day 1; doxorubicin 15mg/m2/d, 4 short infusions, day 1–4; dexamethasone 160mg total dose orally) and G-CSF (Neupogen 600mg/d s.c. or Granocyte 526mg/d s.c., day 5 after the end of chemotherapy until PBSC). Thal was stopped two weeks before CAD. Low dose heparine was administered to prevent deep venous thromboses in the TAD group. RESULTS: The median time was 14 days after the first day of CAD until PBSC in patients in both the TAD (range 12–18 days) and VAD group (range 10–19 days). In the first leukapheresis, a median total PBSC yield of 8,1x106/kg CD34+ cells in the TAD/CAD (range 0,3–34x106 CD34+ cells) and 8,7x106/kg CD34+ cells in the VAD/CAD (range 0,5–30x106 CD34+ cells) group could be harvested (p=0.31). In the best leukapheresis, a median total PBSC yield of 8,1x106/kg CD34+ cells in the TAD/CAD (range 0,7–34x106 CD34+ cells) and 8,9x106/kg CD34+ cells in the VAD/CAD (range 2–30x106 CD34+ cells) group could be reached (p=0.24). CONCLUSIONS: No difference was found in stem cell collection and yield after TAD versus VAD. Thalidomide as a part of induction therapy does not seem to have an influence of the peripheral blood stem cell collection of patients with multiple myeloma.

Mobilisation of Autologous Stem Cells Using a Single Fixed Dose Injection of Pegfilgrastim; Feasibility in Extensively Pre-Treated Lymphoma and Myeloma Patients.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5220-5220 ◽  
Author(s):  
Paula F. Ypma ◽  
Arif A. Muradin ◽  
P.W. Wijermans
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Stem Cell ◽  
Single Dose ◽  
Optimal Dose ◽  
Fixed Dose ◽  
High Dose ◽  
Peripheral Blood Stem Cells ◽  
Cd34 Cells ◽  
Pre Treatment

Abstract In patients with multiple myeloma and refractory or relapsed lymphoma consolidation high-dose chemotherapy combined with stem cell rescue is an established therapy in chemosensitive disease. A commonly used approach to mobilise CD34+ haematopoietic stem cells is the administration of granulocyte colony-stimulating factor following a course of chemotherapy. Pegylation of filgrastim decreases renal clearance of the molecule. Pegfilgrastim is subject to a distinct method of clearance compared to filgrastim. The clearance therefore depends almost solely on a neutrophil receptor mediated process. This means clearance is self-regulated and increases when the number of neutrophils with G-CSF receptors augments in the blood. In earlier series of patients, pegfilgrastim showed to be effective in mobilising blood progenitor cells in single fixed doses of 6 mg. as well as 12 mg. The optimal dose and scheduling of the injection and apheresis is not completely established in various patients groups with diverse extents of chemotherapeutic pre-treatment. In this study we compared the mobilisation kinetics of patients with different haematological malignancies using either filgrastim or one injection of pegfilgrastim in two different doses. 58 patients with various indications for autologous stem cell transplantation were studied. The transplantation indications were multiple myeloma, NHL and Hodgkin’s lymphoma. Patients received a single dose of either 6 mgs or 12 mgs of pegfilgrastim; a third group of patients was treated with filgrastim daily. Filgrastim administration was stopped as soon as sufficient numbers of stem cells were harvested. Harvesting in both groups started as soon as an absolute CD 34+ count of >1 × 107 per litre was reached. The required number of stem cells was 3 × 106/kg bodyweight (6 × 106/kg in multiple myeloma patients). Mobilisation kinetics and apheresis results were compared in the three groups. The one-way analysis of variance (ANOVA) was used to compare the data. 26 Patients received a single dose of 6 mgs pegfilgrastim and 10 patients received a dose of 12 mgs of pegfilgrastim. 22 Patients, matched for disease type and pre-treatment regimens, age and gender received filgrastim daily. The filgrastim was administered in an average total dose of 4,2 mgs. (7,7 m gr./kg/day). Table 1 shows results of the apheresis. Of 26 patients who received pegfilgrastim 6 mgs, 5 patients showed a failure mobilising stemcells (21%). In 2 of those 5 patients harvesting succeeded eventually after additional stimulation with filgrastim and another 2 patients were mobilised in a later stage after additional chemopriming and filgrastim in high dosage. One of the patients receiving 12 mgs. of pegfilgrastim also needed additional filgrastim administration. None of the filgrastim mobilisation procedures failed. The results indicate that a single dose pegfilgrastim of 6 mgs is not capable of mobilising sufficient peripheral blood stem cells in all patients. In this study, both doses of pegfilgrastim showed a reduced CD34 cells harvest and less efficient apheresis procedures. Table 1: Results Apheresis pegfilgrastim pegfilgrastim filgrastim 6 mg (n=26) 12 mg (n=10) (n=22) * p<0,05 day 1st apheresis, mean (SD) * 12.2 (1.4) 12.1 (0.9) 13.5 (2.4) max. blood CD34+ count (×107/L), mean (SD) 8.6 (7,7) 7.9 (6,6) 11.6 (10) number CD34+ cells (×106/kg), mean (SD) 8.2 (4.6) 8 (2,5) 11 (6,2) number CD34+ cells (×106/kg)per litre proc. volume, mean (SD) * 440 (290) 461 (350) 797 (650) failure apheresis 5 1 0

Peripheral Blood Stem Cell (PBSC) Harvest Is More Expensive Following Bortezomib-Based Therapy in Multiple Myeloma (MM), Related to Increase Number of Days of Collect.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1373-1373
Author(s):  
Matthieu Barthelemy ◽  
Florence Boulanger ◽  
Houria Debarri ◽  
Laurent Pascal ◽  
Pierre Samarcq ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Induction Therapy ◽  
Young Patients ◽  
Standard Of Care ◽  
Induction Treatment ◽  
High Dose ◽  
Front Line ◽  
History Of ◽  
The Cost

Abstract Abstract 1373 Poster Board I-395 Background: High-dose therapy is the front line treatment of reference in young patients with Multiple Myeloma (MM). Although induction therapy remains a matter of controversy, bortezomib-based therapy is considered more and more as a standard of care. Prior to autologous stem cell transplantation (ASCT), patients undergo PBSC collect, usually starting after cycle 2 to 4 of the induction treatment. Currently, patients receive one transplant at front line, but most of the patients will benefit throughout the MM disease history of a second or a third ASCT procedure. We have noticed that the number of days of collection vary from patient-to-patient following bortezomib-based induction therapy. This increase in collection procedures might increase the cost of PBSC harvest with more patients discomfort and staff unavailability. We have therefore further studied the quality, yields and days of collection in myeloma patients following bortezomib-based therapy as compared to other regimens-based treatment courses. Material and Method: We retrospectively studied 70 patients with myeloma that underwent PBSC harvestsafter mobilization with GCSF following debulking with bortezomib-based therapy (58 days of procedures – 26 patients) versus other agents-based therapy [65 days of procedure – 44 patients; VAD vincristine, adriamycin, dexamethasone). Results: -Yields. CD34 Mobilization is lower following bortezomib-based therapy as compared to other regimen-based therapy. Similarly, more days of collection are also needed to collect the requested yield of PBSC. -Engrafment. No significant differences regarding engraftment was noticed among the 2 groups studied. The days to neutrophil and platelet counts recovery, the number of days with fever and the number of red cell and platelet transfusions were not significantly different between the 2 groups, mobilization following bortezomib-based therapy versus other regimen-based therapy, respectively. Conclusion: In our series, bortezomib-based induction regimen does not increase the number of PBSC harvest failure and the quality of engraftment was identical to other regimen-based induction treatment. However, CD34 mobilization was lower following bortezomib-based therapy, which explains lower daily harvest counts and therefore an increase number of days of collection in bortezomib-based treated patients. Therefore, PBSC harvest procedure following bortezomib-based therapy significantly increases the cost of PBSC collection. These results need to be confirmed in larger studies. New agents in use for mobilization might be considered for future PBSC collection in bortezomib-based treated patients. Disclosures: Leleu: Janssen Cilag: Research Funding.

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 &gt; 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 &gt; 2 sessions (P= 0.005). The number of the patients who collected &gt; 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 &gt; 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.

Chemotherapy Combined with Granulocyte Colony Stimulating Factor (G-CSF) for Mobilization of CD34+ Cells in Lymphoma and Multiple Myeloma Patients

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5441-5441
Author(s):  
Gaofeng Zheng ◽  
Yanlong Zheng ◽  
Yi Luo ◽  
Jimin Shi ◽  
Weiyan Zheng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Stem Cell ◽  
Success Rate ◽  
Peripheral Blood ◽  
Hodgkin's Lymphoma ◽  
Collection Rate ◽  
Cd34 Cells ◽  
Stem Cell Collection ◽  
The Ideal

Abstract Objective: To investigate and analyze factors which effect autologous stem cell collection in patients with lymphoma and multiple myeloma (MM) during chemotherapy combined with G-CSF mobilization, for improving quality and effectiveness of autologous stem cell transplantation. Methods: A retrospective analysis was performed from April 1, 2006 to October 31, 2013 in our hospital and 128 lymphoma and MM patients whose autologous peripheral blood stem cells (PBSCs) were collected including 75 patients with malignant lymphoma,7 cases of Hodgkin's lymphoma and 68 non-Hodgkin's lymphoma (NHL) cases as well as 53 MM patients were enrolled. The stem cells of all patients were mobilized by chemotherapy combined with G-CSF and collected via a continuous flow cell separation instrument (COBE Spectra, Lakewood, CO). Mobilize failure was defined when the amount of CD34 + cells was less than 2.0 x 106 / kg, whereas ≥2.0 * 106 / kg was defined as successful mobilization. More than 5.0x 106 cells / kg or more was considrered as ideal mobilization. Univariate and multivariate regression analyses of factors for mobilization failure, successful mobilization and ideal mobilization acquisition were performed. Results: There were more CD34+ cells in MM patients than in lymphoma patients (P = 0.064). The collection rates of CD34 + cells in MM patients were ≥ 2.0 x106 / kg in 64.8% (83 cases) and ≥ 5.0 x 106 / kg in 35.2% (45 cases). MM patients with a success collection ratio was 73.6 % (39/53) and the ideal collection rate was 43.4% (23/53), which was higher than in the NHL group with a success rate and ideal rate of 58.7% (44/75) and 30.7% (23/75). A total of 35.2 % (45 cases, including 31MM cases and 14 lymphoma cases) a mobilization was not successful. Conclusion: In different chemotherapy regimens in patients with lymphoma, remission, ever use MTX and/or Ara-c treatment and collecting the outer peripheral hematocrit could significantly affect the success rate of stem cell collection; In MM patients, who received lenalidomide treatment and multiple courses of treatment, still not got CR, which these reasons were the factors of non- successful mobilization.Although Plerixafor and peripheral blood CD34-positive cell counts could help to improve the success collection rate and predict collection rate, but there is still a need for further improvement of the current mobilization protocols, recognizing the ideal stem cell collection dynamics, efficiency and cost in order to select the appropriate mobilization protocols. Disclosures No relevant conflicts of interest to declare.

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