Peripheral Blood Progenitor Cell Mobilization of CD34+ Cells with Combine G-CSF and GM-CSF in Pediatric Patient with Different Types of Cancer

Abstract Abstract 3223 Poster Board III-160 There are concerns that prolonged exposure to lenalidomide (len) impairs the peripheral blood progenitor cell (PBPC) yield in patients (pts) undergoing autologous peripheral blood stem cell transplant (ASCT) for multiple myeloma. To evaluate the effect of len on PBPC yield, we retrospectively analyzed 144 consecutive pts undergoing PBPC harvest prior to ASCT for multiple myeloma between July 1, 2007 and June 30, 2009. Exclusion criteria included prior ASCT or prior treatment with an alkylating agent. Of the evaluable patients, 67 pts received at least one cycle of len as part of their pre-harvest therapy (median # of cycles 4 (range 1-28)) and 63 received non-len containing regimens. Median age for all pts was 57 years and was similar between the two groups. Initial PBPC harvest was unsuccessful (defined as collection of <2.5 × 106 CD34+ cells/kg) in 6 of 52 (11.5%) G-CSF mobilized pts who had prior len exposure, compared to 4 of 49 (8.2%) non-len exposed pts mobilized with G-CSF (p = NS). One pt in each group underwent ASCT after collection of <2.5 × 106 CD34+ cells/kg and both engrafted normally. One other cyclophosphamide/G-CSF mobilized and len exposed pt failed initial harvest as well. Of the 11 total pts in whom initial PBPC harvest failed, a second attempt was successful in 10 (3 G-CSF/GM-CSF; 6 plerixafor/G-CSF; 1 cyclophosphamide/G-CSF) and not attempted in 1. The median number of PBPCs harvested in len exposed pts mobilized with G-CSF alone was 6.36 × 106 CD34+ cells/kg (range 2.1-20.62), compared to 8.22 × 106 CD34+ cells/kg (range 2.29-46.1) in non-len exposed pts mobilized with G-CSF alone (p=0.001 by Mann-Whitney test). Len treated pts required more apheresis sessions for adequate PBPC harvest (1.89 days vs 1.57 days (p<0.05)) than non-len treated pts when G-CSF was used alone as the mobilizing agent. Eleven (24%) of the len treated pts and 6 (13%) of the non-len treated pts were not able to collect ≥ 5.0 × 106 CD34+ cells/kg with G-CSF alone (p=0.42). Among 10 G-CSF mobilized pts who received >6 cycles (median # of cycles 11, range 7-28) of len prior to PBPC harvest, the median PBPC yield was 6.44 × 106 CD34+ cells/kg collected over a median of 2 days. Seven of the 10 collected enough PBPCs for two transplants. One pt receiving 7 cycles of len failed initial PBPC harvest with G-CSF alone and subsequently successfully harvested with plerixafor/G-CSF. Nineteen pts were initially mobilized for PBPC harvest with cyclophosphamide/G-CSF. Nine had prior len exposure (median # of cycles 4 (range 3-8)) and the PBPC yield for each pt was well above that required for tandem ASCT. There was no difference in the number of days to harvest between the len treated and non-len treated pts and most harvested in 1 apheresis attempt. One patient with 4 cycles of prior len therapy did not collect an adequate number of PBPCs but subsequently successfully harvested enough PBPCs for 2 ASCTs with plerixafor/G-CSF. In summary, most pts treated with len containing regimens prior to PBPC harvest were able to collect adequate numbers of PBPCs for tandem ASCT with G-CSF mobilization. All len treated pts in our series who failed G-CSF mobilization and underwent a second attempt at PBPC harvest using plerixafor/G-CSF or cyclophosphamide/G-CSF as the mobilizing agent were able to successfully harvest adequate numbers of PBPCs for ASCT. In this retrospective review, the difference in PBPC yield between len treated and non-len treated pts did not impact the ability to proceed to ASCT. Disclosures Off Label Use: Cyclophosphamide for stem cell mobilization. Zonder:Millennium: Research Funding; Amgen, Pfizer, Cephalon: Consultancy; Millennium, Celgene: Speakers Bureau. Abidi:Millennium: Speakers Bureau; Amgen, Merck: Research Funding; Genzyme, Millennium: Consultancy.

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Hematological recovery and peripheral blood progenitor cell mobilization after induction chemotherapy and GM-CSF plus G-CSF in breast cancer

Bone Marrow Transplantation ◽

10.1038/sj.bmt.1702205 ◽

2000 ◽

Vol 25 (7) ◽

pp. 705-710 ◽

Cited By ~ 2

Author(s):

S Charrier ◽

P Chollet ◽

J-O Bay ◽

H Curé ◽

F Kwiatkowski ◽

...

Keyword(s):

Breast Cancer ◽

Induction Chemotherapy ◽

Peripheral Blood ◽

Progenitor Cell ◽

Peripheral Blood Progenitor Cell ◽

Gm Csf ◽

Cell Mobilization

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Plerixafor Salvage Is Safe and Effective in Hard-to-Mobilize Patients Undergoing Chemotherapy and Filgrastim-Based Peripheral Blood Progenitor Cell Mobilization

Journal of Oncology ◽

10.1155/2012/931071 ◽

2012 ◽

Vol 2012 ◽

pp. 1-5 ◽

Cited By ~ 7

Author(s):

Farrukh T. Awan ◽

S. Thomas Kochuparambil ◽

David DeRemer ◽

Aaron Cumpston ◽

Michael Craig ◽

...

Keyword(s):

Peripheral Blood ◽

Progenitor Cell ◽

Peripheral Blood Progenitor Cell ◽

Cell Mobilization

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Randomized comparison of progenitor-cell mobilization using chemotherapy, stem-cell factor, and filgrastim or chemotherapy plus filgrastim alone in patients with ovarian cancer.

Journal of Clinical Oncology ◽

10.1200/jco.1998.16.8.2601 ◽

1998 ◽

Vol 16 (8) ◽

pp. 2601-2612 ◽

Cited By ~ 33

Author(s):

A Weaver ◽

J Chang ◽

E Wrigley ◽

E de Wynter ◽

P J Woll ◽

...

Keyword(s):

Ovarian Cancer ◽

Stem Cell ◽

Peripheral Blood ◽

Stem Cell Factor ◽

Progenitor Cell ◽

Randomized Study ◽

Cd34 Cells ◽

Cell Mobilization ◽

High Yields ◽

Higher Doses

PURPOSE This was the first randomized study to investigate the efficacy of peripheral-blood progenitor cell (PBPC) mobilization using stem-cell factor (SCF) in combination with filgrastim (G-CSF) following chemotherapy compared with filgrastim alone following chemotherapy. PATIENTS AND METHODS Forty-eight patients with ovarian cancer were treated with cyclophosphamide and randomized to receive filgrastim 5 microg/kg alone or filgrastim 5 microg/kg plus SCF. The dose of SCF was cohort-dependent (5, 10, 15, and 20 microg/kg), with 12 patients in each cohort, nine of whom received SCF plus filgrastim and the remaining three patients who received filgrastim alone. On recovery from the WBC nadir, patients underwent a single apheresis. RESULTS SCF in combination with filgrastim following chemotherapy enhanced the mobilization of progenitor cells compared with that produced by filgrastim alone following chemotherapy. This enhancement was dose-dependent for colony-forming unit-granulocyte-macrophage (CFU-GM), burst-forming unit-erythrocyte (BFU-E), and CD34+ cells in both the peripheral blood and apheresis product. In the apheresis product, threefold to fivefold increases in median CD34+ and progenitor cell yields were obtained in patients treated with SCF 20 microg/kg plus filgrastim compared with yields obtained in patients treated with filgrastim alone. Peripheral blood values of CFU-GM, BFU-E, and CD34+ cells per milliliter remained above defined threshold levels longer with higher doses of SCF. The higher doses of SCF offer a greater window of opportunity in which to perform the apheresis to achieve high yields. CONCLUSION SCF (15 or 20 microg/kg) in combination with filgrastim following chemotherapy is an effective way of increasing progenitor cell yields compared with filgrastim alone following chemotherapy.

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Megakaryocytic Progenitors Can Be Generated Ex Vivo and Safely Administered to Autologous Peripheral Blood Progenitor Cell Transplant Recipients

Blood ◽

10.1182/blood.v89.8.2679 ◽

1997 ◽

Vol 89 (8) ◽

pp. 2679-2688 ◽

Cited By ~ 129

Author(s):

Francesco Bertolini ◽

Manuela Battaglia ◽

Paolo Pedrazzoli ◽

Gian Antonio Da Prada ◽

Annalisa Lanza ◽

...

Keyword(s):

Cell Cultures ◽

Peripheral Blood ◽

Platelet Transfusion ◽

Progenitor Cell ◽

Ex Vivo ◽

Peripheral Blood Progenitor Cell ◽

Control Group ◽

Cell Transplant ◽

Transplant Recipients ◽

Cd34 Cells

Abstract We evaluated different culture conditions to obtain a lineage-selected proliferation of clonogenic megakaryocytic progenitors (MP). In low-density (LD) or CD34+ cell cultures, the best results were obtained in serum-free medium in the presence of megakaryocyte growth and development factor, stem cell factor, interleukin-3 (IL-3), IL-6, IL-11, FLT-ligand, and macrophage inflammatory protein-1α. In paired studies, expansion of LD cells was less effective than expansion of CD34+ cells, and pre-enrichment of CD34+ cells using negative depletion of lineage-positive cells produced significantly larger quantities of MP than pre-enrichment using positive selection. MP proliferation peaked on day 7 in culture, and an 8- ± 5-fold expansion of CD34+/CD61+ cells, a 17- ± 5-fold expansion of colony-forming units-megakaryocytes, and a 58- ± 14-fold expansion of the total number of CD61+ cells was obtained. In a feasibility clinical study, 10 cancer patients (8 with breast cancer and 2 with non-Hodgkin's lymphoma) undergoing autologous peripheral blood progenitor cell (PBPC) transplant received MP generated ex vivo (range, 1 to 21 × 105/kg CD61+ cells) together with unmanipulated PBPC. Eight patients received a single allogeneic platelet transfusion, whereas platelet transfusion support was not needed in 2 of the 4 patients receiving the highest doses of cultured MP. This result compares favorably with a retrospective control group of 14 patients, all requiring platelet transfusion support. Adverse reactions or bacterial contamination of cell cultures have not been observed. In conclusion, MP can be expanded ex vivo and safely administered to autologous transplant recipients. Further clinical trials will indicate the reinfusion schedule able to consistently abrogate the need for allogeneic platelet transfusion support in autologous transplantation.

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Sustained long-term hematopoiesis after myeloablative therapy with peripheral blood progenitor cell support

Blood ◽

10.1182/blood.v85.12.3754.bloodjournal85123754 ◽

1995 ◽

Vol 85 (12) ◽

pp. 3754-3761 ◽

Cited By ~ 72

Author(s):

R Haas ◽

B Witt ◽

R Mohle ◽

H Goldschmidt ◽

S Hohaus ◽

...

Keyword(s):

Bone Marrow ◽

Peripheral Blood ◽

Progenitor Cell ◽

Lymphoblastic Leukemia ◽

Peripheral Blood Progenitor Cell ◽

Myelogenous Leukemia ◽

High Dose ◽

Platelet Recovery ◽

Cd34 Cells

A retrospective analysis of long-term hematopoiesis was performed in a group of 145 consecutive patients who had received high-dose therapy with peripheral blood progenitor cell (PBPC) support between May 1985 and December 1993. Twenty-two patients had acute myelogenous leukemia, nine had acute lymphoblastic leukemia, 43 had Hodgkin's disease, 57 had non- Hodgkin's lymphoma, and 14 patients had multiple myeloma. Eighty-four patients were male and 61 female, with a median age of 37 years (range, 16 to 58 years). In 46 patients, PBPC were collected after cytotoxic chemotherapy alone, while 99 patients received cytokines either during steady-state hematopoiesis or post-chemotherapy. Sixty patients were treated with dose-escalated polychemotherapy, and 85 patients had a conditioning therapy including hyperfractionated total body irradiation at a total dose of 14.4 Gy. The duration of severe pancytopenia posttransplantation was inversely related to the number of reinfused granulocyte-macrophage colony-forming units (CFU-GM) and CD34+ cells. Threshold quantities of 2.5 x 10(6) CD34+ cells per kilogram or 12.0 x 10(4) CFU-GM per kilogram became evident and were associated with rapid neutrophil and platelet recovery within less than 18 and 14 days, respectively. These numbers were also predictive for long-term reconstitution, indicating that normal blood counts are likely to be achieved within less than 10 months after transplantation. Conversely, 12 patients were autografted with a median of 1.75 x 10(4) CFU-GM per kilogram resulting in delayed recovery to platelet counts of greater than 150 x 10(9)/L between 1 and 6 years. Our study includes bone marrow examinations in 50 patients performed at a median follow-up time of 10 months (range, 1 to 85 months) posttransplantation. A comparison with normal volunteers showed a 3.2-fold smaller proportion of bone marrow CD34+ cells, which was paralleled by an even more pronounced reduction in the plating efficiency of CFU-GM and burst-forming unit-erythroid. No secondary graft failure was observed, even in patients autografted with relatively low numbers of progenitor cells. This suggests that either the pretransplant regimens were not myeloablative, allowing autochthonous recovery, or that a small number of cells capable of perpetual self-renewal were included in the autograft products.

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An analysis of engraftment kinetics as a function of the CD34 content of peripheral blood progenitor cell collections in 692 patients after the administration of myeloablative chemotherapy

Blood ◽

10.1182/blood.v86.10.3961.bloodjournal86103961 ◽

1995 ◽

Vol 86 (10) ◽

pp. 3961-3969 ◽

Cited By ~ 454

Author(s):

CH Weaver ◽

B Hazelton ◽

R Birch ◽

P Palmer ◽

C Allen ◽

...

Keyword(s):

Peripheral Blood ◽

Progenitor Cell ◽

Cox Regression ◽

Peripheral Blood Progenitor Cell ◽

High Dose ◽

Reference Laboratory ◽

Cell Content ◽

Platelet Recovery ◽

Cd34 Cells ◽

Kinetics Of

The CD34 antigen is expressed by committed and uncommitted hematopoietic progenitor cells and is increasingly used to assess stem cell content of peripheral blood progenitor cell (PBPC) collections. Quantitative CD34 expression in PBPC collections has been suggested to correlate with engraftment kinetics of PBPCs infused after myeloablative therapy. We analyzed the engraftment kinetics as a function of CD34 content in 692 patients treated with high-dose chemotherapy (HDC). Patients had PBPCs collected after cyclophosphamide based mobilization chemotherapy with or without recombinant human granulocyte colony-stimulating factor (rhG-CSF) until > or = 2.5 x 10(6) CD34+ cells/kg were harvested. Measurement of the CD34 content of PBPC collections was performed daily by a central reference laboratory using a single technique of CD34 analysis. Forty-five patients required a second mobilization procedure to achieve > or = 2.5 x 10(6) CD34+ cells/kg and 15 patients with less than 2.5 x 10(6) CD34+ cells/kg available for infusion received HDC. A median of 9.94 x 10(6) CD34+ cells/kg (range, 0.5 to 112.6 x 10(6) CD34+ cells/kg) contained in the PBPC collections was subsequently infused into patients after the administration of HDC. Engraftment was rapid with patients requiring a median of 9 days (range, 5 to 38 days) to achieve a neutrophil count of 0.5 x 10(9)/L and a median of 9 days (range, 4 to 53+ days) to achieve a platelet count of > or = 20 x 10(9)/L. A clear dose-response relationship was evident between the number of CD34+ cells per kilogram infused between the number of CD34+ cells per kilogram infused and neutrophil and platelet engraftment kinetics. Factors potentially influencing the engraftment kinetics of neutrophil and platelet recovery were examined using a Cox regression model. The single most powerful mediator of both platelet (P = .0001) and neutrophil (P = .0001) recovery was the CD34 content of the PBPC product. Administration of a post-PBPC infusion myeloid growth factor was also highly correlated with neutrophil recovery (P = .0001). Patients receiving high-dose cyclophosphamide, thiotepa, and carboplatin had more rapid platelet recovery than patients receiving other regimens (P = .006), and patients requiring 2 mobilization procedures versus 1 mobilization procedure to achieve > or = 2.5 x 10(6) CD34+ cells/kg experienced slower platelet recovery (P = .005). Although a minimal threshold CD34 dose could not be defined, > or = 5.0 x 10(6) CD34+ cells/kg appears to be optimal for ensuring rapid neutrophil and platelet recovery.

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