IL-3 plus GM-CSF Induced Recruitment of High Numbers of Peripheral Blood Progenitor Cells Following Standard Dose Chemotherapy

1993 ◽  
pp. 168-176 ◽  
Author(s):  
W. Brugger ◽  
R. Mertelsmann ◽  
L. Kanz
Keyword(s):  
Progenitor Cells ◽  
Peripheral Blood ◽  
Standard Dose ◽  
Gm Csf ◽  
Peripheral Blood Progenitor Cells

Mobilization of peripheral blood progenitor cells by sequential administration of interleukin-3 and granulocyte-macrophage colony- stimulating factor following polychemotherapy with etoposide, ifosfamide, and cisplatin [see comments]

Blood ◽  
1992 ◽  
Vol 79 (5) ◽  
pp. 1193-1200 ◽  
Author(s):  
W Brugger ◽  
K Bross ◽  
J Frisch ◽  
P Dern ◽  
B Weber ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Peripheral Blood ◽  
Standard Dose ◽  
Gm Csf ◽  
Peripheral Blood Progenitor Cells ◽  
Cd34 Cells ◽  
Sequential Administration ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Abstract We report on the requirements that have to be met to combine a standard- dose chemotherapy regimen with broad antitumor activity with the mobilization of peripheral blood hematopoietic progenitor cells. Thirty- two cancer patients were given a 1-day course of chemotherapy consisting of etoposide (VP16), ifosfamide, and cisplatin (VIP; n = 46 cycles), followed by the combined sequential administration of recombinant human interleukin-3 (rhIL-3) and recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF). Control patients received GM-CSF alone or were treated without cytokines. Maximum numbers of peripheral blood progenitor cells (PBPC) were recruited on day 13 to 17 after chemotherapy, with a median of 418 CD34+ cells/microL blood (range, 106 to 1,841) in IL-3/GM-CSF-treated patients, 426 CD34+/microL (range, 191 to 1,380) in GM-CSF-treated patients, and 46 CD34+/microL (range, 15 to 148) in patients treated without cytokines. In parallel, there was an increase in myeloid (10,490 colony-forming unit-granulocyte-macrophage [CFU-GM]/mL blood; range, 1,000 to 23,400), as well as erythroid (10,660 burst-forming unit-erythroid [BFU-E]/mL blood; range, 3,870 to 24,300) and multipotential (840 CFU-granulocyte, erythrocyte, monocyte, megakaryocyte [GEMM]/mL blood; range, 160 to 2,070) progenitor cells in IL-3 plus GM-CSF-treated patients. In GM-CSF-treated patients, significantly less precursor cells of all lineages were mobilized, particularly multipotential progenitors (400 CFU-GEMM/mL blood; range, 200 to 2,150). Only small numbers of CD34+ cells and clonogenic progenitor cells could be recruited in intensively pretreated patients. Our data document that after standard-dose chemotherapy-induced bone marrow hypoplasia, IL-3 plus GM-CSF can be used to recruit PBPC, which might shorten the hematopoietic recovery after high-dose chemotherapy in chemosensitive lymphomas or solid tumors.

scholarly journals Mobilization of peripheral blood progenitor cells by sequential administration of interleukin-3 and granulocyte-macrophage colony- stimulating factor following polychemotherapy with etoposide, ifosfamide, and cisplatin [see comments]

Blood ◽  
1992 ◽  
Vol 79 (5) ◽  
pp. 1193-1200 ◽  
Author(s):  
W Brugger ◽  
K Bross ◽  
J Frisch ◽  
P Dern ◽  
B Weber ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Peripheral Blood ◽  
Standard Dose ◽  
Gm Csf ◽  
Peripheral Blood Progenitor Cells ◽  
Cd34 Cells ◽  
Sequential Administration ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

We report on the requirements that have to be met to combine a standard- dose chemotherapy regimen with broad antitumor activity with the mobilization of peripheral blood hematopoietic progenitor cells. Thirty- two cancer patients were given a 1-day course of chemotherapy consisting of etoposide (VP16), ifosfamide, and cisplatin (VIP; n = 46 cycles), followed by the combined sequential administration of recombinant human interleukin-3 (rhIL-3) and recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF). Control patients received GM-CSF alone or were treated without cytokines. Maximum numbers of peripheral blood progenitor cells (PBPC) were recruited on day 13 to 17 after chemotherapy, with a median of 418 CD34+ cells/microL blood (range, 106 to 1,841) in IL-3/GM-CSF-treated patients, 426 CD34+/microL (range, 191 to 1,380) in GM-CSF-treated patients, and 46 CD34+/microL (range, 15 to 148) in patients treated without cytokines. In parallel, there was an increase in myeloid (10,490 colony-forming unit-granulocyte-macrophage [CFU-GM]/mL blood; range, 1,000 to 23,400), as well as erythroid (10,660 burst-forming unit-erythroid [BFU-E]/mL blood; range, 3,870 to 24,300) and multipotential (840 CFU-granulocyte, erythrocyte, monocyte, megakaryocyte [GEMM]/mL blood; range, 160 to 2,070) progenitor cells in IL-3 plus GM-CSF-treated patients. In GM-CSF-treated patients, significantly less precursor cells of all lineages were mobilized, particularly multipotential progenitors (400 CFU-GEMM/mL blood; range, 200 to 2,150). Only small numbers of CD34+ cells and clonogenic progenitor cells could be recruited in intensively pretreated patients. Our data document that after standard-dose chemotherapy-induced bone marrow hypoplasia, IL-3 plus GM-CSF can be used to recruit PBPC, which might shorten the hematopoietic recovery after high-dose chemotherapy in chemosensitive lymphomas or solid tumors.

High- Versus Standard-Dose Filgrastim (rhG-CSF) for Mobilization of Peripheral-Blood Progenitor Cells From Allogeneic Donors and CD34+ Immunoselection

1999 ◽  
Vol 17 (7) ◽  
pp. 2160-2160 ◽  
Author(s):  
Monika Engelhardt ◽  
Hartmut Bertz ◽  
Matthias Afting ◽  
Cornelius F. Waller ◽  
Jürgen Finke
Keyword(s):  
Progenitor Cells ◽  
Peripheral Blood ◽  
Standard Dose ◽  
Allogeneic Transplantation ◽  
Selection Procedures ◽  
Once Daily ◽  
Cell Numbers ◽  
Peripheral Blood Progenitor Cells ◽  
Group A ◽  
Group B

PURPOSE: The efficacy of a high- versus a standard-dose filgrastim (recombinant human granulocyte colony-stimulating factor, or rhG-CSF) regimen to mobilize peripheral-blood progenitor cells (PBPCs) for allogeneic transplantation was investigated in 75 healthy donors. PATIENTS AND METHODS: From December 1994 to December 1997, 75 consecutive donors (median age, 38 years; range, 17 to 67 years) were assigned to two different schedules of rhG-CSF for PBPC mobilization. Fifty donors received 24 μg rhG-CSF/kg body weight (BW) divided into two daily subcutaneous injections (two doses of 12 μg, group A), whereas 25 were treated with 10 μg rhG-CSF once daily (group B). Apheresis was started on day 4 in group A and on day 5 in group B. Target CD34+ cell numbers in apheresis products were ≥ 4 × 106/kg recipient BW. RESULTS: Cytokine priming and collection of PBPCs were equally well tolerated in both groups. Significantly higher CD34+ cell numbers in group A with 3.7 × 106/kg recipient BW/apheresis (0.47 × 106/L apheresis) compared with 2 × 106/kg recipient BW/apheresis (0.25 × 106/L apharesis) in group B were obtained (P < .05). Using standard aphereses (median, 9 L), two doses of 12 μg rhG-CSF/kg allowed collection of ≥ 4 × 106/kg CD34+ cells with two aphereses (range, one to three) in group A versus three aphereses (range, one to six) in group B (P < .015). Donor age, sex, and BW influenced the collection of CD34+ cell numbers: in particular, significantly higher apheresis results were obtained in donors younger than 40 years compared with donors older than 40 years of age (P < .05). In 65 CD34+ selection procedures using avidin-biotin immunoabsorption columns (Ceprate SC System, CellPro, Bothell, WA), a median CD34+ purity of 53%, CD34+ recovery of 40%, and the collection of 2 × 106/kg CD34+ cells/selection were achieved. In group A with higher CD34+ cells/kg/apheresis, CD34+ purity, recovery, and cell yields were 60%, 45%, and 2.3 × 106/kg/selection, respectively, as compared with 48%, 31%, and 0.7 × 106/kg in group B (P < .05). CONCLUSION: Our results demonstrate that twice daily rhG-CSF (two doses of 12 μg/kg BM) compared with once daily rhG-CSF (10 μg/kg BW), in addition to being well tolerated, significantly improves PBPC mobilization, allows the collection of higher numbers of CD34+ cells with one or two standard aphereses, and facilitates subsequent selection procedures in healthy allogeneic donors.

Use of peripheral-blood progenitor cells abrogates the myelotoxicity of repetitive outpatient high-dose carboplatin and cyclophosphamide chemotherapy.

1993 ◽  
Vol 11 (8) ◽  
pp. 1583-1591 ◽  
Author(s):  
I Tepler ◽  
S A Cannistra ◽  
E Frei ◽  
R Gonin ◽  
K C Anderson ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Peripheral Blood ◽  
Disease Onset ◽  
Dose Intensity ◽  
Outpatient Setting ◽  
High Dose ◽  
Hematologic Toxicity ◽  
Intensive Chemotherapy ◽  
Gm Csf ◽  
Peripheral Blood Progenitor Cells

PURPOSE Attempts to increase dose-intensity in clinical practice have been limited by cumulative hematologic toxicity despite the use of hematopoietic growth factors. To address this problem, we designed a study to determine whether four cycles of dose-intensive chemotherapy with carboplatin could be administered in the outpatient setting using granulocyte-macrophage colony-stimulating factor (GM-CSF) and peripheral-blood progenitor cells (PBPCs) that had been harvested before initiation of treatment. PATIENTS AND METHODS An initial cycle (cycle no. 0) of cyclophosphamide 4 g/m2 followed by GM-CSF was used to mobilize PBPCs harvested by leukapheresis for 6 consecutive days. Cycles no. 1 through 4 consisted of outpatient carboplatin 600 mg/m2 and cyclophosphamide 600 mg/m2 followed by GM-CSF 5 micrograms/kg subcutaneously (SC) twice per day every 28 days. In cycle no. 1, PBPC were not reinfused to assess the effects of GM-CSF alone. In cycles no. 2 through 4, PBPCs were reinfused on day 3 in an outpatient setting. RESULTS In eight assessable patients, the addition of PBPCs in cycle no. 2 resulted in a significant reduction in the median duration of thrombocytopenia less than 20,000/microL (6.5 v 1 day; P = .016), days to platelets more than 50,000/microL (20.5 v 15 days; P = .020), number of platelet transfusions (five v 1.5; P = .016), and duration of neutropenia (absolute neutrophil count [ANC] < 1,000/microL (7 v 2.5 days; P = .008) when compared with cycle no. 1. Dose-limiting hematologic toxicity, defined as more than 7 days of platelets less than 20,000/microL or ANC less than 500/microL, was observed in four of eight patients during cycle no. 1, but not during cycles no. 2, 3, and 4 of chemotherapy supported by PBPCs (a total of 19 cycles in eight patients). Five of eight patients completed all four cycles of high-dose therapy. Three patients did not complete four cycles due to late thrombocytopenia (n = 2) or tumor progression (n = 1). CONCLUSION These results indicate a benefit of PBPCs in addition to GM-CSF in alleviating myelosuppression of dose-intensive chemotherapy. Initial collection of PBPCs may allow administration of repetitive cycles of high-dose chemotherapy with acceptable toxicity to outpatients at disease onset.

Improvement of hematologic recovery after high-dose intensification using peripheral blood progenitor cells (PBPC) mobilized by chemotherapy and GM-CSF

1994 ◽  
Vol 69 (6) ◽  
pp. 297-302 ◽  
Author(s):  
T. Lamy ◽  
B. Drenou ◽  
I. Grulois ◽  
C. Leberre ◽  
C. Dauriac ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Peripheral Blood ◽  
High Dose ◽  
Dose Intensification ◽  
Gm Csf ◽  
Peripheral Blood Progenitor Cells

Sequential cycles of high-dose carboplatin administered with recombinant human granulocyte-macrophage colony-stimulating factor and repeated infusions of autologous peripheral-blood progenitor cells: a novel and effective method for delivering multiple courses of dose-intensive therapy.

1992 ◽  
Vol 10 (3) ◽  
pp. 464-473 ◽  
Author(s):  
T C Shea ◽  
J R Mason ◽  
A M Storniolo ◽  
B Newton ◽  
M Breslin ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Peripheral Blood ◽  
High Dose ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Peripheral Blood Progenitor Cells ◽  
Multiple Cycles ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

PURPOSE The trial was undertaken to study the effect of administering granulocyte-macrophage colony-stimulating factor (GM-CSF) with and without peripheral-blood progenitor cells (PBPC) on the hematologic and nonhematologic toxicity observed with multiple cycles of high-dose carboplatin chemotherapy. PATIENTS AND METHODS Eighteen patients with a variety of solid tumors received a total of 40 cycles of carboplatin, 1,200 mg/m2 per cycle, administered by continuous infusion over 96 hours. All 40 courses were administered with a daily 4-hour intravenous (IV) infusion of either 5 or 10 micrograms/kg/d of recombinant human Escherichia coli-derived GM-CSF. The first 20 courses were administered without PBPC support (treatment A). Because of severe neutropenia and thrombocytopenia, the next 20 courses of therapy were administered with GM-CSF, PBPC, and oral antibiotic prophylaxis (treatment B). RESULTS The addition of PBPC support led to a significant reduction in the duration of neutropenia (10.5 v 7.5 days; P = .027) and thrombocytopenia (12.4 v 5.2 days; P = .001), number of RBC transfusions (six v three; P = .01) and platelet transfusions (10.3 v 3.7; P = .013), number of hospital days (12.6 v 2.9; P = .01), and days of IV antibiotics (11.8 v 2.4; P = .007) per cycle. Significant increases in the weekly dose intensity (206 v 285 mg/m2/wk; P = .014) and total dose (2,287 v 3,600 mg/m2; P = .018) of carboplatin delivered were also observed with treatment B. The overall response rate in this study was 70%, with 11 of 16 assessable patients achieving either a complete (three patients) or partial (eight patients) remission. CONCLUSION This combination of GM-CSF and PBPC infusion represents an effective method for delivering multiple cycles of high-dose carboplatin chemotherapy and may serve as a model for the administration of high-dose chemotherapy in future trials.

Reinfusion and serial measurements of carboplatin-mobilized peripheral-blood progenitor cells in patients receiving multiple cycles of high-dose chemotherapy.

1994 ◽  
Vol 12 (5) ◽  
pp. 1012-1020 ◽  
Author(s):  
T C Shea ◽  
J R Mason ◽  
M Breslin ◽  
E Bissent ◽  
M Mullen ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Inverse Correlation ◽  
High Dose ◽  
Hematologic Toxicity ◽  
Gm Csf ◽  
Peripheral Blood Progenitor Cells ◽  
Multiple Cycles ◽  
The Impact

PURPOSE To examine the ability of carboplatin to mobilize peripheral-blood progenitor cells (PBPCs) and to examine the impact of infusing these cells on myelosuppression following multiple cycles of high-dose therapy. Fluctuations in circulating progenitor cell concentration following repeated cycles of this therapy were also measured. PATIENTS AND METHODS Eight patients received a total of 20 cycles of carboplatin 1,200 mg/m2 per course, granulocyte-macrophage colony-stimulating factor (GM-CSF) 5 micrograms/kg/d, and PBPC reinfusion every 28 days. PBPC were collected following 1 week of GM-CSF and following the first and second cycles of chemotherapy. Hematologic toxicity was correlated with the number of progenitor cells reinfused per cycle. The concentration of PBPC per milliliter of blood was measured at study entry, following GM-CSF priming, and after each cycle of chemotherapy. RESULTS We observed a strong inverse correlation between the number of PBPCs (CD34 and colony-forming unit granulocyte-macrophage [CFU-GM]), but not mononuclear cells (MNCs) reinfused and the days with neutropenia less than 500/microL and platelets less than 20,000/microL. Compared with baseline levels, the circulating PBPC concentration increased up to 27-fold following the first course of chemotherapy, but decreased toward, and eventually below, baseline following the second and third cycles of carboplatin. CONCLUSION PBPC reinfusion directly correlated with a reduction in myelosuppression following high-dose carboplatin chemotherapy. While high-dose carboplatin plus GM-CSF leads to a substantially greater mobilization of PBPC than GM-CSF alone, this effect is lost after multiple treatment cycles. These results emphasize the importance of early procurement and value of PBPC reinfusion in conjunction with multiple cycles of dose-intensive chemotherapy.

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