Kinetics of Autologous Stem Cell Mobilization Failure: Comparison of AMD3100/G-CSF, G-CSF, GM-/G-CSF, and Chemotherapy/G-CSF on Remobilization Success.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3380-3380 ◽  
Author(s):  
John F. DiPersio ◽  
Angela Smith ◽  
Dianne Sempek ◽  
Albert Baker ◽  
Steven Jiang ◽  
...  
Keyword(s):  
Stem Cell ◽  
Surrogate Marker ◽  
Median Number ◽  
High Dose Chemotherapy ◽  
Disease State ◽  
High Dose ◽  
Factors Associated ◽  
Cd34 Cells ◽  
Cell Mobilization ◽  
Kinetics Of

Abstract Background: No standard approach for the mobilization of peripheral hematologic stem and progenitor cells (HSPCs) has been established. High levels of circulating CD34+ cells, a surrogate marker for mobilization efficiency, are associated with less apheresis days. A higher dose of CD34+ cell transfused after high-dose chemotherapy decreases time to hematologic recovery. Consequently, a better understanding of variables associated with mobilization kinetics may further optimize stem cell collection and reduce complications associated with autologous stem cell transplants. Methods: The Washington University (St. Louis, MO) transplantation database includes clinical parameters from 407 multiple myeloma (MM), 567 non-Hodgkin’s Lymphoma (NHL), and 164 Hodgkin’s disease (HD) pts who received an ASCT between 1995 and 2006. A retrospective analysis of this large pt population was conducted to determine factors associated with the mobilization kinetics of CD34+ cells. Results: Figure 1 summarizes the mobilization kinetics as defined by number of days to reach a target of 2 × 10^6 CD34+ cells/kg. Overall, the median number of aphereses to reach the target were 1, 2, and 2 in MM, NHL, and HD, respectively. Daily median CD34+ yields in MM pts were 3.8, 1.2, and 0.5 × 10^6 on day 1–3, respectively. In NHL pts, yields were 1.4, 0.8, and 0.4 × 10^6 on day 1–3. In HD pts, yields were 1.8, 0.8, and 0.3 × 10^6 on day 1–3, respectively. The addition of chemotherapy increased the % of pts requiring only a single apheresis to reach the mobilization target. Figure 2 summarizes the mobilization kinetics for each re-mobilization regimen. In general, a limited number of cells was collected with each aphereses; >70% of pts failed to mobilize 2 × 10^6 CD34+ cells/kg. In contrast, remobilization with AMD3100 allowed the collection of sufficient CD34+ cells in 67% of pts; median number of apheresis to reach the target was 3. Conclusions: Factors associated with mobilization kinetics of CD34+ cells include disease state and mobilization regimen. Re-mobilization is associated with high failure rates, re-mobilization regimens including AMD3100 are more successful. Figure 1: Mobilization kinetics by disease state Figure 1:. Mobilization kinetics by disease state Figure 2: Mobilization kinetics by re-mobilization regimen Figure 2:. Mobilization kinetics by re-mobilization regimen

Impact of Disease and Mobilizing Agents on Initial and Remobilization Failure.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5222-5222
Author(s):  
John F. DiPersio ◽  
Angela Smith ◽  
Dianne Sempek ◽  
Albert Baker ◽  
Steven Jiang ◽  
...  
Keyword(s):  
Failure Rate ◽  
Surrogate Marker ◽  
High Dose Chemotherapy ◽  
Disease State ◽  
High Dose ◽  
Failure Rates ◽  
Gm Csf ◽  
Scheffe Test ◽  
Cd34 Cells ◽  
Significant Difference

Abstract Background: High-dose chemotherapy with autologous stem cell transplantation (ASCT) is a widely used treatment strategy in lymphoma and myeloma; however, no standard approach for the mobilization of peripheral hematologic stem and progenitor cells (HSPCs) has been established. Levels of circulating CD34+ cells, a surrogate marker for mobilization efficiency, vary widely between pts, and may be influenced by disease state, prior therapy, and/or mobilization regimen. Methods: The Washington University (St. Louis, MO) transplantation database includes clinical parameters from 407 multiple myeloma (MM), 562 non-Hodgkin’s Lymphoma (NHL), and 164 Hodgkin’s disease (HD) pts who received an ASCT between 1995 and 2006. A retrospective analysis of this large (1133 pts) population was conducted to determine factors associated with mobilization efficiency. Mobilization failure was defined as collection of < 2 × 10^6 CD34+ cells/kg within 5 apheresis days. Statistical analysis included analysis of variance (ANOVA) with Scheffe Test to determine differences in mobilization between the various mobilization regimens (G-CSF, G-CSF/chemotherapy, G-/GM-CSF, G-CSF/AMD3100). Results: All pts were included in the analysis; 87% received G-CSF alone as the initial mobilization regimen. Mobilization failure rates are summarized in Table 1. NHL and HD pts had an approx. 4-fold higher failure rate than MM pts. The combination of G-CSF with chemotherapy increased the median CD34+ yield compared to G-CSF alone, although no obvious impact on the failure rate was noted in this relatively small group of pts. Remobilization was associated with high failure rates in NHL (79.2%), HD (77.1%), and MM (73.3%). Pooled collections were <2 × 10^6 CD34+/kg in 33.6%, 37.1%, and 36.7% of failed mobilizers, respectively. ANOVA analysis indicated a significant difference in outcome based on remobilization regimen. A post hoc comparison using the Scheffe Test determined that G-CSF mobilization failures remobilized with G-CSF plus AMD3100 collected significantly more CD34+ cells than G-CSF-failures remobilized with either G-CSF, G/GM-CSF or G-CSF/chemo (1-way ANOVA: F(3, 233) = 27.878, F0.5(3, 233).05 = 2.643, p < .0001). The compared groups did not significantly differ in initial mobilization efficiency with G-CSF (as determined by ANOVA and Scheffe Test). Conclusions: The mobilization failure rate is substantially higher in NHL and HD pts than MM pts. Pts who fail initial mobilization are highly likely to fail a 2nd mobilization, regardless of disease state. As the combination of chemotherapy to G-CSF may not be sufficient to reduce failure rates, alternative mobilization strategies are needed to improve HSPC collection, particularly in NHL/HD pts and failed mobilizers. First mobilization failure rates (< 2×10^6 CD34+/kg) Mobilization regimen N Failures Median yield (×10^6) 95% C.I (×10^6) * Incl. pts mobilized w. alternative regimens NHL G-CSF 471 26.5% 2.89 2.76–3.04 G-CSF/Chemo 35 22.9% 4.68 2.8–8.53 All* 564 28.7% HD G-CSF 130 26.2% 3.01 2.75–3.37 G-CSF/Chemo 12 16.7% 5.38 2.35–9.52 All* 165 24.8% MM G-CSF 386 6.5% 4.62 4.16–4.98 G-CSF/Chemo 17 5.9% 8.52 4.46–16.3 All* 409 6.6%

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.

Autologous transplantation of granulocyte colony-stimulating factor–primed bone marrow is effective in supporting myeloablative chemotherapy in patients with hematologic malignancies and poor peripheral blood stem cell mobilization

Blood ◽  
2003 ◽  
Vol 102 (5) ◽  
pp. 1595-1600 ◽  
Author(s):  
Roberto M. Lemoli ◽  
Antonio de Vivo ◽  
Daniela Damiani ◽  
Alessandro Isidori ◽  
Monica Tani ◽  
...  
Keyword(s):  
Stem Cell ◽  
Peripheral Blood Stem Cell ◽  
High Dose Chemotherapy ◽  
Stem Cell Mobilization ◽  
High Dose ◽  
Myeloablative Chemotherapy ◽  
Hematopoietic Recovery ◽  
Cd34 Cells ◽  
Cell Mobilization ◽  
Stimulating Factor

AbstractWe assessed the hematopoietic recovery and transplantation-related mortality (TRM) of patients who had failed peripheral blood stem cell mobilization and subsequently received high-dose chemotherapy supported by granulocyte colony-stimulating factor (G-CSF)–primed bone marrow (BM). Studied were 86 heavily pretreated consecutive patients with acute leukemia (n = 21), refractory/relapsed non-Hodgkin lymphoma (n = 41) and Hodgkin disease (n = 17), and multiple myeloma (n = 7). There were 78 patients who showed insufficient mobilization of CD34+ cells (&lt; 10 cells/μL), whereas 8 patients collected less than 1 × 106 CD34+ cells/kg. BM was primed in vivo for 3 days with 15 to 16 μg/kg of subcutaneous G-CSF. Median numbers of nucleated cells, colony-forming unit cells (CFU-Cs), and CD34+ cells per kilogram harvested were 3.5 × 108, 3.72 × 104, and 0.82 × 106, respectively. Following myeloablative chemotherapy, median times to achieve a granulocyte count higher than 0.5 × 109/L and an unsupported platelet count higher than 20 and 50 × 109/L were 13 (range, 8-24), 15 (range, 12-75), and 22 (range, 12-180) days, respectively, for lymphoma/myeloma patients and 23 (range, 13-53), 52 (range, 40-120), and 90 (range, 46-207) days, respectively, for leukemia patients. Median times to hospital discharge after transplantation were 17 (range, 12-40) and 27 (range, 14-39) days for lymphoma/myeloma and acute leukemia patients, respectively. TRM was 4.6%, whereas 15 patients died of disease. G-CSF–primed BM induces effective multilineage hematopoietic recovery after high-dose chemotherapy and can be safely used in patients with poor stem cell mobilization.

Steady State Mobilization of Autologous Blood Stem Cells Using G-CSF and AMD3100 in Patients with Multiple Myeloma (MM).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5219-5219
Author(s):  
Gerhard Ehninger ◽  
Stefan Fruehauf ◽  
Kai Hubel ◽  
Uwe Platzbecker ◽  
Karin Badel ◽  
...  
Keyword(s):  
Stem Cell ◽  
Autologous Blood ◽  
Fold Increase ◽  
Median Number ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Hematopoietic Growth Factors ◽  
Platelet Recovery ◽  
Significant Toxicity ◽  
Cd34 Cells

Abstract Background: High dose chemotherapy with autologous stem cell transplantation (ASCT) improves disease free and overall survival in pts with MM; tandem ASCT may further enhance clinical benefits. Mobilization with G-CSF alone fails to yield sufficient CD34+ cells for a tandem ASCT in the majority of MM pts. A mobilization regimen including G-CSF and cyclophosphamide is more effective, but associated with significant toxicity. This phase II study evaluated the efficacy and safety of a non-cytotoxic mobilization regimen of AMD3100 plus G-CSF for ASC mobilization in pts with MM. Methods: Mobilization treatment consisted of subcutaneous G-CSF (Filgrastim 10 μg/kg) given in the morning on 5 consecutive days and a single dose of AMD3100 (240 μg/kg) in the evening of day 4, 10–11 hours prior to leukapheresis. These procedures could be repeated for up to 5 additional days in order to collect an adequate number of cells for transplantation. Monitoring of CD34+ cells in peripheral blood (PB) was performed immediately prior to each AMD3100 administration and prior to the aphereses. Patients were treated with high dose chemotherapy in preparation for transplantation according to local standard of care guidelines. Pts did not receive hematopoietic growth factors following ASCT. The primary endpoint of the study was safety; secondary endpoints included 1) % of pts with >2-fold increase of CD34+ cells following AMD3100, and 2) % of pts in with hematopoietic recovery between day 14 and day 21. Results: 31 pts were evaluable, including 19 males (median age: 57 yrs, range: 40–73) and 12 females (median age: 61 yrs, range: 53–67). Pts had received a maximum of 4 prior chemotherapy cycles. The cumulative proportion of pts reaching a target of 5×10^6/kg CD34+ cells was 60% on day 1, 87% on day 2, and 93% on day 3. For the initial mobilization, AMD3100 increased absolute CD34+ counts ≥ 2-fold in 78% of pts (median fold increase: 2.8; range: 1.1–15.2). Additional aphereses showed a ≥ 2-fold increase in 21% of cases (median fold increase: 1.4; range: 0.7–6.5). Overall, the median number of CD34+ cells yielded was 7.1×10^6/kg (range: 3–28×10^6/kg). The majority of pts (n=19) underwent only a single apheresis, whereas additional procedures were needed in 12 cases. Nineteen pts received a single transplant, 11 pts a tandem transplant. Autografts contained a median of 3.1×10^6/kg CD34+ cells (range 2.4–9.2×10^6/kg). After first transplant, median time to neutrophil and platelet engraftment was 14 and 13 days, respectively. All patients had complete engraftment within 20 days except 1 pt who had neutrophil recovery at day 34 (single transplant) and 1 had platelet recovery at day 27 after the 2nd transplant. AMD3100 was well tolerated, drug-related adverse events (AEs) were limited to 2 cases of mild nausea/vomiting. Conclusions: The addition of AMD3100 to G-CSF doubled the number of mobilized CD34+ cells in the majority of pts, allowing the collection of sufficient CD34+ cells for tandem ASCT in 1–2 aphereses. Unlike chemotherapeutics commonly used to enhance stem cell mobilization, AMD3100 was not associated with any significant toxicity.

Peripheral Blood Stem Cell Mobilization by G-CSF Alone and Engraftment Kinetics Following Autologous Transplantation in Children and Adolescents with Solid Tumor.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5197-5197
Author(s):  
Hiroyoshi Watanabe ◽  
Tsutomu Watanabe ◽  
Hiroko Suzuya ◽  
Yoshifumi Wakata ◽  
Toshihiro Onishi ◽  
...  
Keyword(s):  
Stem Cell ◽  
Autologous Transplantation ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Platelet Recovery ◽  
Irradiation Group ◽  
Cd34 Cells ◽  
Pediatric Cancer Patients ◽  
Group 3 ◽  
Cell Mobilization

Abstract The purpose of this study was to examine the yield of PBSC, mobilized with G-CSF alone, and engraftment kinetics after autologous transplantation in pediatric cancer patients. In 55 patients (median age; 7 years, range 0–21) with various pediatric and adolescent solid tumors, PBSC were mobilized with G-CSF alone, and the yields of PBSC and engraftment following autologous PBSCT were evaluated retrospectively. Patients were categorized according to prior treatment; patients who had received less than 4 or 4 cycles of chemotherapy with/without local irradiation (Group 1: N= 21), patients who received more than 4 cycles of chemotherapy or 3 or more cycles of chemotherapy with extended irradiation (Group 2: N= 23), and patients who received high-dose chemotherapy with stem cell support (Group 3: N= 11). Ten microgram per kg of G-CSF was injected subcutaneously for mobilization when patients showed no influence of previous chemotherapy, and administration was continued for five days. The peaks of CD34+ cells and CFU-GM were observed on day 5 of G-CSF administration essentially in all patients. Aphereses were performed on days 5 and 6 of G-CSF treatment. Mobilization failure was observed in four patients in all groups. Compared with the results in patients mobilized by chemotherapy plus G-CSF (N=18), the progenitor cell yields were lower in those mobilized with G-CSF alone. However, there were no significant differences in WBC engraftment speed compared to the chemotherapy plus G-CSF mobilization group, although platelet recovery was delayed in patients with G-CSF alone, especially in patients in Group 3. The median time taken for ANC and platelet counts to reach 500 and 20K was 12 days (range 8–28) and 15 days (8–55), respectively, in all patients who were mobilized by G-CSF alone except for patients with progressive disease. In summary, mobilization with G-CSF alone can mobilize a sufficient number of CD34+ cells for successful autografting and sustained hematological reconstitution in pediatric patients with cancer, even in heavily pre-treated patients. Mobilization with G-CSF alone might offer some advantages, such as ease of determining a collection schedule without a daily determination of CD34+ cells in the blood, and the avoidance of neutropenic fever and additional transfusion.

DCEP (Dexamethasone, Cyclophosphamide, Etoposide, Cisplatin) Followed by High-Dose G-CSF Is a Highly Efficient and Safe Regimen for Stem Cell Mobilization for Multiple Myeloma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3284-3284
Author(s):  
Jason P. Gonsky ◽  
Nikoletta Lendvai ◽  
Michele L. Donato ◽  
Scott D. Rowley ◽  
Andrew L. Pecora ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
High Dose Chemotherapy ◽  
High Yield ◽  
High Dose ◽  
Outpatient Basis ◽  
Stem Cell Rescue ◽  
Cd34 Cells ◽  
Cell Mobilization ◽  
Related Mortality

Abstract High dose chemotherapy with autologous stem cell rescue remains a standard therapy for multiple myeloma patients who can tolerate it. A mobilizing regimen for multiple myeloma should ideally allow for a high yield of CD34+ cells, provide anti-myeloma activity, be well tolerated, and have predictable kinetics regarding initiation of collection of stem cells. Higher numbers of infused autologous CD34+ cells allow for more rapid engraftment and lower incidence of transplant-related morbidity and mortality. The goal for patients with myeloma is to harvest enough CD34+ cells to provide at least two autologous transplants. Previous mobilization regimens utilized G-CSF alone or high-dose cyclophosphamide with G-CSF. However, high-dose cyclophosphamide (4–7g/m2) has only modest efficacy against myeloma and is associated with significant morbidity and up to 1–2% treatment-related mortality. DCEP (dexamethasone, cyclophosphamide, etoposide, cisplatin) is a well established regimen with good efficacy as salvage treatment for myeloma. Additionally, the use of DCEP with G-CSF for mobilization in myeloma has previously been reported to provide an average yield of approximately 6x106 CD34+ cells. We report our experience with DCEP and high-dose G-CSF in mobilizing 88 multiple myeloma patients since 2006. Our regimen consisted of 40 mg dexamethasone IV over 15 minutes x 4 days, cyclophosphamide 500 mg/m2, etoposide 40 mg/m2 (capped at 75 mg), and cisplatin 15 mg/m2 (capped at 25 mg), all continuous IV infusions over 24h x 4 days, with G-CSF starting 24–48h after completion of chemotherapy, administered SQ at 5 mcg/kg x 6 days followed by 10 mcg/kg daily until pheresis is completed. Over 80% of our patients were ready to initiate collection on day 14. Our goal for collection is 10–12x106 CD34+ cells to allow for two or three transplants using at least 4x106 CD34+ cells per transplant. Yields were excellent with a mean yield of 27x106 CD34+ cells, with a range of 7.3–130.5x106 CD34+ cells. 37/88 (42%) of patients required only one day of pheresis, with a mean yield of 34x106 CD34+ cells. 38/88 (43%) of patients required two days of pheresis. Only 15% of patients required more than two days of pheresis. Only 3 patients yielded fewer than 10x106 CD34+ cells (3%), and none yielded fewer than 5x106 CD34+ cells. In conclusion, this regimen is highly efficacious, offers excellent stem cell yields and predictable collection kinetics, can be administered on an outpatient basis, and is safe and well tolerated.

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.

Pegfilgrastim Versus Filgrastim To Accelerate Hematopoietic Recovery after High Dose Melphalan and Autologous Hematopoietic Stem Cell Transplant (ASCT) for Multiple Myeloma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5193-5193
Author(s):  
Rebecca L. Olin ◽  
Selina M. Luger ◽  
David L. Porter ◽  
Stephen J. Schuster ◽  
Donald Tsai ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Cohort Study ◽  
Stem Cell ◽  
Retrospective Cohort Study ◽  
Retrospective Cohort ◽  
Median Number ◽  
High Dose ◽  
Hematopoietic Recovery ◽  
Cd34 Cells ◽  
High Dose Melphalan

Abstract High-dose melphalan followed by ASCT is a common component of the early treatment for patients with multiple myeloma. Daily subcutaneous injections of filgrastim (Neupogen) at 5 ug/kg/day until ANC &gt; 500/ul are routinely administered at our center from day +4 following ASCT, in order to accelerate hematopoietic recovery and lessen neutropenic complications. Pegfilgrastim (Neulasta) as a single 6 mg fixed dose subcutaneous injection has been shown to have similar efficacy and ease of use when compared to filgrastim in the non-transplant setting, but little data is available in the transplant setting. We began using pegfilgrastim day +1 following ASCT for patients with multiple myeloma and performed a retrospective cohort study comparing those who received filgrastim (n=6) with those who received pegfilgrastim (n=11). Transplants occurred between July 2002 and January 2004 and included all patients transplanted for myeloma in that time period for whom sufficient data was available. All patients had at least 2 x 106 CD34+ cells/kg peripheral stem cells harvested after cytoxan and filgrastim mobilization. Main outcome measures were: days from stem cell infusion to WBC nadir, days to ANC&gt;500/ul, and days to ANC&gt;1000/ul. Subjects were excluded if CBCs were drawn less frequently than every four days. There were no significant differences between the filgrastim and pegfilgrastim groups with respect to the following demographic variables: age, gender, hemoglobin, creatinine, calcium, albumin and beta-2 microglobulin at diagnosis. The groups were also balanced with respect to SPEP, UPEP, presence of lytic lesions and number of prior lines of therapy. The median number of CD34+ cells infused was similar: 5.7 x 106 in the filgrastim group vs 4.8 x 106 in the pegfilgrastim group (p=0.28). After transplant, median number of days to WBC nadir in the filgrastim group (FG) was 7 (range 5–9) vs 6 (range 5–8) in the pegfilgrastim group (PG) (p=0.31). However, median number of days to ANC&gt;500/ul in the FG was 11.5 (range 11–17) vs 10 (range 9–12) for PG (p=0.02). Similarly, median number of days to ANC&gt;1000/ul was 12 (range 11–17) for FG vs 11 (range 10–13) for PG (p=0.03). Five of six patients in the FG had neutropenic fever after transplant, compared to five of eleven patients in the PG (p=0.30). Currently, no significant differences in infection or relapse rates between groups have been noted and there were no deaths in either group. In this retrospective cohort study, pegfilgrastim was safe and at least equivalent to filgrastim for accelerating hematopoiesis after ASCT for multiple myeloma. Furthermore, there was no significant difference in the incidence of neutropenic fever, infection and survival, suggesting a similar clinical utility.

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