Ancestim (r-metHuSCF) in Combination with Filgrastim To Rescue Mobilization and Collection of Peripheral Blood Progenitor Cells for Autologous Transplantation. Compassionate Use in 372 Patients at 68 Sites in France (1998–2004).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2923-2923 ◽  
Author(s):  
Jean-Francois Rossi ◽  
Karima Safsafi ◽  
Peter Royce ◽  
Jean Caraux ◽  
Keyword(s):  
Peripheral Blood ◽  
Autologous Transplantation ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Compassionate Use ◽  
Peripheral Blood Progenitor Cells ◽  
Cd34 Cells ◽  
The Mean ◽  
Cell Support ◽  
L 13

Abstract High-dose chemotherapy (HDC) requires hematopoïetic stem cell support. Failure of mobilization was defined by CD34+ cells <20/μL, and failure of collection by CD34+ collected cells <2.106 cells/kg. In one center, 92 of 742 mobilization candidates in 5 years failed in mobilization/collection (classical parameters including age & previous line(s)-mean: 12.2%, range/year: 8.1–19.3%). In addition, 44/92 pts had an estimation of their CD34+ cell bone marrow (BM) content by a 2 to 3-site BM aspirate, allowing to subdivide pts with a defect of mobilization with persisting CD34+ in BM from pts with a lack of CD34+ cells in BM, corresponding to a true BM failure. Ancestim (r-metHuSCF, Amgen, CA) functions synergistically with filgrastim to mobilize progenitors to the peripheral blood. To evaluate a combination ancestim + filgrastim as rescue in the generation of a PBPC autograft in pts with prior failure to mobilize CD34+ cells, or from whom insufficient CD34+ cells had been collected, we performed the following analysis. Ancestim was delivered with the ATU (named pt French Temporary Authorization for Use) program to 372 pts (median age 53 yrs [1–70]; females 49%). Diseases categories were: lymphomas (Ly: 50%), multiple myeloma (MM,29%); CLL (6%), Ewing’s sarcoma (4%), neuroblastomas (4%), ovarian carcinoma (1%), other tumor (6%). 357 pts were analyzed: 339 pts having prior collection failure (number of prior failure of leukapheresis: 1 to 5), and 18 pts for whom stem cells mobilization failed and no prior leukapheresis. Ancestim (20μg/kg/d) was combined with filgrastim alone (10μg/kg/d; median 7 days) or with chemotherapy + filgrastim (5μg/kg/d, median 12 days). An autograft appropriate to support HDC (>2x106 CD34+ cells/kg) was obtained in 144/357 pts (40%) following an ancestim administration − 9 of 18 pts with prior mobilization failure(s) &135 of 339 pts with prior collection failure(s) (including 56% MM and 29% Ly) - The mean of CD34+ cells obtained was 3.26 x106/Kg. In the 339 pts with prior collection failure, the ancestim + filgrastim association was efficacious concerning the collection in 65% pts. To date, 115 pts have undergone transplantation (106 pts in the group of prior collection failure and 9 pts in the second group). Median times to platelet and neutrophil recovery were comparable to those obtained with filgrastim-mobilized PBPCs (platelets > 20 x 109/L-13 days; neutrophils > 0.5 109/L-12 days). Of the 22 evaluate pts with CLL who experienced mobilization failure, an adequate autograft was obtained in 10 pts, followed by an autotransplantation in 5 pts. Safety Amgen data report (459 pts with prior mobilization or collection failure have been exposed to ancestim) 2 experienced anaphylactoid symptoms with systemic histamine release, after inadvertant IV injection. In this population with prior failure for an autograft, an additional mobilization of progenitors using ancestim + filgrastim was tried to obtain an appropriate collection for an autograft and allow HDC progression, even in pts who failed previous mobilization(s). With an appropriate premedication, use of ancestim was safe in this large multicenter series.

scholarly journals Selection and expansion of peripheral blood CD34+ cells in autologous stem cell transplantation for breast cancer

Blood ◽  
1996 ◽  
Vol 87 (5) ◽  
pp. 1687-1691 ◽  
Author(s):  
SF Williams ◽  
WJ Lee ◽  
JG Bender ◽  
T Zimmerman ◽  
P Swinney ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Peripheral Blood ◽  
Cultured Cells ◽  
Ex Vivo ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Platelet Counts ◽  
Cd34 Cells ◽  
The Mean

Abstract Cytopenia after high-dose chemotherapy and autologous stem cell reinfusion is a major cause of morbidity. Ex vivo cultured expansion and differentiation of CD34+ peripheral blood progenitor cells (PBPC) to neutrophil precursors may shorten the neutropenic period further. We explored the use of these ex vivo cultured PBPCs in nine patients with metastatic breast cancer. All underwent PBPC mobilization with cyclophosphamide, VP-16, and G-CSF. Subsequently, they underwent four to five apheresis procedures. One apheresis product from each patient was prepared using the Isolex 300 Magnetic Cell Separation System (Baxter Immunotherapy, Irvine, CA) to obtain CD34+ cells. These cells were then cultured in gas permeable bags containing serum-free X-VIVO 10 (BioWhittaker, Walkersville, MD) medium supplemented with 1% human serum albumin and 100 ng/mL PIXY321. At day 12 of culture the mean fold expansion was 26x with a range of 6 to 64x. One patient's cells did not expand because of a technical difficulty. The final cell product contained an average of 29.3% CD15+ neutrophil precursors with a range of 18.5% to 48.1%. The patients underwent high-dose chemotherapy with cyclophosphamide, carboplatin, and thiotepa. On day 0, the cryopreserved PBPCs were reinfused and on day +1 the 12-day cultured cells were washed, resuspended, and reinfused into eight of nine patients. One patient was not infused with cultured cells. The mean number of cultured cells reinfused was 44.6 x 10(6) cells/kg with a range of 0.8 to 156.6 x 10(6) cells/kg. No toxicity was observed after reinfusion. The eight patients have recovered absolute neutrophil counts > 500/microL on a median of 8 days (range 8 to 10 days); the median platelet transfusion independence occurred on day 10 (range 8 to 12 days) and platelet counts > 50,000/microL were achieved by day 12 (range 9 to 14) for the seven patients whose platelet counts could be determined. Expanded CD34+ selected PBPC can be obtained and safely reinfused into patients.

Fixed-Dose Single Agent Pegfilgrastim for Peripheral Blood Progenitor Cell Mobilization in Patients with Multiple Myeloma (MM).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2923-2923
Author(s):  
Chitra Hosing ◽  
Muzaffar H. Qazilbash ◽  
Partow Kebriaei ◽  
Sergio Giralt ◽  
Marilyn S. Davis ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Median Time ◽  
Peripheral Blood ◽  
Progenitor Cell ◽  
Autologous Transplantation ◽  
High Dose Chemotherapy ◽  
Fixed Dose ◽  
High Dose ◽  
Cell Dose ◽  
Cd34 Cells

Abstract High-dose chemotherapy and autologous peripheral blood progenitor cell (APBPC) transplantation is an effective treatment for MM. Progenitor cells are generally mobilized in to the blood by administration of filgrastim alone or after chemotherapy. Since the half-life of filgrastim is 3–4 hours, daily SC injections are required until completion of apheresis. Pegylated filgrastim (Neulasta™; Amgen Inc., Thousand Oaks, CA, USA) is a covalent conjugate of filgrastim and monomethoxypolyethylene glycol, with a half-life of about 33 hours. Preliminary data suggests that a single SC injection of pegfilgrastim may mobilize progenitor cells without added toxicity and thus avoid the need for repeated injections. We performed a phase II study of pegfilgrastim administered as a single SC injection to mobilize APBPC. PATIENTS AND METHODS. Patients with MM, who were to undergo high-dose chemotherapy and APBPCT were studied. Patients were required to have a PS of &lt; 3 (ECOG), adequate hematological (WBC &gt; 3.5 x 109/l; platelet count &gt; 100 x 109/l) and adequate organ function. Patients whose prior therapy included thalidomide, dexamethasone and bortezomib were eligible. The protocol was IRB approved and all patients signed informed consent. Because of the rare cases of splenic rupture associated with high-dose filgrastim, patients were also required to have a maximum spleen size of &lt; 12 cm in the greatest dimension by radiographic imaging as stipulated by the FDA. All patients were given single SC fixed-dose of 12 mg pegfilgrastim. Circulating CD34+ cell levels were assessed daily starting day +2 after the pegfilgrastim. Leukapheresis was started when the PB CD34+ count was greater than 15/μL. Leukapheresis employed standard procedures using 3 times the total blood volume. Daily leukapheresis was performed until the target pheresis cell dose of at least 6 x 106 CD34+ cells/kg was reached for patients planned for tandem APBPCT and at least 3 x 106 for single transplant procedure. High-dose chemotherapy comprised of melphalan (200 mg/m2) alone or in combination with arsenic trioxide. All patients received filgrastim 5 mcg/kg/day SC starting at day 0 after stem cell infusion. RESULTS: Between 1/04 and 3/05, 19 patients (13 M /6 F) with a median age of 57.5 years (range, 34.5–77.4) were entered on the study. The median time to reach a PB CD34 count of 15/μL was 3 days (range, 2–4). The median number of leukapheresis procedures required was 2 (range, 1–5). The median collection of CD34+ cells was 8.4 x 106 (range, 4.1–15.8). The median CD34+ cell dose collected/L of blood processed was 19.3 (range, 6.4 – 77.4). Most common toxicity was bone pain in 6/19 patients (maximum grade 3). Reversible liver enzyme elevations were seen in all patients. At the time of this report 15/19 patients have undergone autologous transplantation with a follow-up of 100 days. The median CD34+ cell dose infused was 4.2 x 106/kg (range, 2.6–9.4). Median time to ANC ≥ 0.5 x 109/l was 10 days (range, 9–11 days) and median time to platelet counts ≥ 20 x 109/l was 11 days (range, 0–17). CONCLUSIONS: A single fixed-dose of pegfilgrastim was effective in mobilizing adequate peripheral blood progenitor cells in patients with MM. The efficacy and toxicity profile was similar to that seen with filgrastim. Rapid and sustained engraftment was seen in all patients following autologous transplantation.

scholarly journals Selection and expansion of peripheral blood CD34+ cells in autologous stem cell transplantation for breast cancer

Blood ◽  
1996 ◽  
Vol 87 (5) ◽  
pp. 1687-1691 ◽  
Author(s):  
SF Williams ◽  
WJ Lee ◽  
JG Bender ◽  
T Zimmerman ◽  
P Swinney ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Peripheral Blood ◽  
Cultured Cells ◽  
Ex Vivo ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Platelet Counts ◽  
Cd34 Cells ◽  
The Mean

Cytopenia after high-dose chemotherapy and autologous stem cell reinfusion is a major cause of morbidity. Ex vivo cultured expansion and differentiation of CD34+ peripheral blood progenitor cells (PBPC) to neutrophil precursors may shorten the neutropenic period further. We explored the use of these ex vivo cultured PBPCs in nine patients with metastatic breast cancer. All underwent PBPC mobilization with cyclophosphamide, VP-16, and G-CSF. Subsequently, they underwent four to five apheresis procedures. One apheresis product from each patient was prepared using the Isolex 300 Magnetic Cell Separation System (Baxter Immunotherapy, Irvine, CA) to obtain CD34+ cells. These cells were then cultured in gas permeable bags containing serum-free X-VIVO 10 (BioWhittaker, Walkersville, MD) medium supplemented with 1% human serum albumin and 100 ng/mL PIXY321. At day 12 of culture the mean fold expansion was 26x with a range of 6 to 64x. One patient's cells did not expand because of a technical difficulty. The final cell product contained an average of 29.3% CD15+ neutrophil precursors with a range of 18.5% to 48.1%. The patients underwent high-dose chemotherapy with cyclophosphamide, carboplatin, and thiotepa. On day 0, the cryopreserved PBPCs were reinfused and on day +1 the 12-day cultured cells were washed, resuspended, and reinfused into eight of nine patients. One patient was not infused with cultured cells. The mean number of cultured cells reinfused was 44.6 x 10(6) cells/kg with a range of 0.8 to 156.6 x 10(6) cells/kg. No toxicity was observed after reinfusion. The eight patients have recovered absolute neutrophil counts > 500/microL on a median of 8 days (range 8 to 10 days); the median platelet transfusion independence occurred on day 10 (range 8 to 12 days) and platelet counts > 50,000/microL were achieved by day 12 (range 9 to 14) for the seven patients whose platelet counts could be determined. Expanded CD34+ selected PBPC can be obtained and safely reinfused into patients.

scholarly journals High CD34+ Cell Counts Decrease Hematologic Toxicity of Autologous Peripheral Blood Progenitor Cell Transplantation

Blood ◽  
1998 ◽  
Vol 91 (9) ◽  
pp. 3148-3155 ◽  
Author(s):  
Nicolas Ketterer ◽  
Gilles Salles ◽  
Michel Raba ◽  
Daniel Espinouse ◽  
Anne Sonet ◽  
...  
Keyword(s):  
Peripheral Blood ◽  
Progenitor Cell ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Lymphoproliferative Diseases ◽  
High Group ◽  
Platelet Recovery ◽  
Neutrophil Recovery ◽  
Intermediate Group ◽  
Cd34 Cells

Optimal numbers of CD34+ cells to be reinfused in patients undergoing peripheral blood progenitor cell (PBPC) transplantation after high-dose chemotherapy are still unknown. Hematologic reconstitution of 168 transplantations performed in patients with lymphoproliferative diseases was analyzed according to the number of CD34+ cells reinfused. The number of days from PBPC reinfusion until neutrophil recovery (>1.0 × 109/L) and unsustained platelet recovery (>50 × 109/L) were analyzed in three groups defined by the number of CD34+ cells reinfused: a low group with less than or equal to 2.5 × 106 CD34+ cells/kg, a high group with greater than 15 × 106 CD34+cells/kg, and an intermediate group to which the former two groups were compared. The 22 low-group patients had a significantly delayed neutrophil (P < .0001) and platelet recovery (P < .0001). The 41 high-group patients experienced significantly shorter engraftment compared with the intermediate group with a median of 11 (range, 8 to 16) versus 12 (range, 7 to 17) days for neutrophil recovery (P = .003), and a median of 11 (range, 7 to 24) versus 14 (range, 8 to 180+) days for platelet recovery (P< .0001). These patients required significantly less platelet transfusions (P = .002). In a multivariate analysis, the amount of CD34+ cells reinfused was the only variable showing significance for neutrophil and platelet recovery. High-group patients had a shorter hospital stay (P = .01) and tended to need fewer days of antibotic administration (P = .12). In conclusion, these results suggest that reinfusion of greater than 15 × 106 CD34+ cells/kg after high-dose chemotherapy for lymphoproliferative diseases further shortens hematopoietic reconstitution, reduces platelet requirements, and may improve patients' quality of life.

scholarly journals High CD34+ Cell Counts Decrease Hematologic Toxicity of Autologous Peripheral Blood Progenitor Cell Transplantation

Blood ◽  
1998 ◽  
Vol 91 (9) ◽  
pp. 3148-3155 ◽  
Author(s):  
Nicolas Ketterer ◽  
Gilles Salles ◽  
Michel Raba ◽  
Daniel Espinouse ◽  
Anne Sonet ◽  
...  
Keyword(s):  
Peripheral Blood ◽  
Progenitor Cell ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Lymphoproliferative Diseases ◽  
High Group ◽  
Platelet Recovery ◽  
Neutrophil Recovery ◽  
Intermediate Group ◽  
Cd34 Cells

Abstract Optimal numbers of CD34+ cells to be reinfused in patients undergoing peripheral blood progenitor cell (PBPC) transplantation after high-dose chemotherapy are still unknown. Hematologic reconstitution of 168 transplantations performed in patients with lymphoproliferative diseases was analyzed according to the number of CD34+ cells reinfused. The number of days from PBPC reinfusion until neutrophil recovery (>1.0 × 109/L) and unsustained platelet recovery (>50 × 109/L) were analyzed in three groups defined by the number of CD34+ cells reinfused: a low group with less than or equal to 2.5 × 106 CD34+ cells/kg, a high group with greater than 15 × 106 CD34+cells/kg, and an intermediate group to which the former two groups were compared. The 22 low-group patients had a significantly delayed neutrophil (P < .0001) and platelet recovery (P < .0001). The 41 high-group patients experienced significantly shorter engraftment compared with the intermediate group with a median of 11 (range, 8 to 16) versus 12 (range, 7 to 17) days for neutrophil recovery (P = .003), and a median of 11 (range, 7 to 24) versus 14 (range, 8 to 180+) days for platelet recovery (P< .0001). These patients required significantly less platelet transfusions (P = .002). In a multivariate analysis, the amount of CD34+ cells reinfused was the only variable showing significance for neutrophil and platelet recovery. High-group patients had a shorter hospital stay (P = .01) and tended to need fewer days of antibotic administration (P = .12). In conclusion, these results suggest that reinfusion of greater than 15 × 106 CD34+ cells/kg after high-dose chemotherapy for lymphoproliferative diseases further shortens hematopoietic reconstitution, reduces platelet requirements, and may improve patients' quality of life.

Quantization of CD34+ Peripheral Blood Hematopoietic Progenitors for Autografting in Cancer Patients

1993 ◽  
Vol 16 (5_suppl) ◽  
pp. 80-82 ◽  
Author(s):  
M. Di Nicola ◽  
S. Siena ◽  
M. Bregni ◽  
F. Peccatori ◽  
M. Magni ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Peripheral Blood ◽  
Autologous Transplantation ◽  
High Dose Chemotherapy ◽  
Direct Immunofluorescence ◽  
High Dose ◽  
Hematopoietic Progenitors ◽  
Flow Cytometry Assay ◽  
Real Time Information ◽  
Time Information

After myeloablative regimens, combined reinfusion of peripheral blood hematopoietic circulating progenitor cells (CPC) and bone marrow, yields a very rapid hematopoietic recovery. Therefore, based on the knowledge that CPC express the CD34 and CD33 differentiation antigen, we have developed a direct immunofluorescence flow cytometry assay to detect the peak of CPC in the peripheral blood of patients treated with high dose chemotherapy and growth factors. This assay, compared to CFU-GM assay, has the following advantages: 1) easy to do 2) standardized method 3) real time information on CPC number. This work illustrates the practical aspects of this assay and substantiate the widespread use of the CD34/33 flow cytometry assay to guide harvesting of circulating hematopoietic progenitors for autologous transplantation.

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