Peripheral Blood Progenitor Cell Yield Research Articles

Selection and use of chemotherapy with hematopoietic growth factors for mobilization of peripheral blood progenitor cells.

Peripheral blood progenitor cells (PBPCs) have become the preferred means of stem cell support for high-dose chemotherapy in recent years. The biology of PBPC mobilization is complex and may be influenced by several variables. Signals from both stromal and hemopoietic cells may induce downregulation of adhesion molecules and upregulate the expression of metalloproteinases. Cytokines alone can mobilize PBPCs but a synergistic effect has been shown when they are used in conjunction with chemotherapy. Disease-specific mobilization strategies appear to have the advantage of less toxicity, greater stem cell yield, and enhanced antitumor activity. Studies have demonstrated that the number of peripheral blood CD34+ cells can be used as a predictor for the timing of apheresis and for estimating PBPC yield. Similarly the CD34+ cell dose is the strongest predictor of hematologic recovery after PBPC transplant. Age, prior radiotherapy, marrow involvement, and prior chemotherapy (especially with alkylating agents) are important factors influencing the yield of stem cells.

Stem Cell Factor in Combination With Filgrastim After Chemotherapy Improves Peripheral Blood Progenitor Cell Yield and Reduces Apheresis Requirements in Multiple Myeloma Patients: A Randomized, Controlled Trial

AbstractStem cell factor (SCF) has been shown to synergize with filgrastim to mobilize CD34+ cells into the peripheral blood. To determine if addition of SCF to chemotherapy and filgrastim reduces the number of leukaphereses required to achieve a target yield of 5 × 106 CD34+ cells/kg, 102 patients with multiple myeloma were randomized to receive mobilization chemotherapy with cyclophosphamide (4 g/m2) and either SCF (20 μg/kg/d) combined with filgrastim (5 μg/kg/d) or filgrastim alone (5 μg/kg/d), administered daily until leukaphereses were completed. After collection, patients were treated with myeloablative therapy supported by autologous peripheral blood progenitor cell (PBPC) infusion and filgrastim (5 μg/kg/d). There was a significant difference between the treatment groups in the number of leukaphereses required to collect 5 × 106 CD34+ cells/kg (median of 1 v 2 for SCF + filgrastim and filgrastim alone, respectively, P = .008). Patients receiving the combination of SCF plus filgrastim had a 3-fold greater chance of reaching 5 × 106 CD34+ cells/kg in a single leukapheresis compared with patients mobilized with filgrastim alone. The median CD34+ cell yield was significantly increased for the SCF group in the first leukapheresis (11.3 v 4.0 × 106/kg, P = .003) and all leukaphereses (12.4v 8.2 × 106/kg, P = .007). Total colony-forming unit–granulocyte-macrophage (CFU-GM) and mononuclear cell counts were also significantly higher in the SCF group in the first leukapheresis and in all leukaphereses. As expected for patients mobilized to an optimal CD34+ cell yield, the time to engraftment was similar between the 2 treatment groups. Cells mobilized with the combination of SCF plus filgrastim were thus considered effective and safe for achieving rapid engraftment. Treatment with SCF plus filgrastim was well tolerated, with mild to moderate injection site reactions being the most frequently reported adverse events. There were no serious allergic-like reactions to SCF. The addition of SCF to filgrastim after cyclophosphamide for PBPC mobilization resulted in a significant increase in CD34+cell yield and a concomitant reduction in the number of leukaphereses required to collect an optimal harvest of 5 × 106CD34+ cells/kg.

Stem Cell Factor in Combination With Filgrastim After Chemotherapy Improves Peripheral Blood Progenitor Cell Yield and Reduces Apheresis Requirements in Multiple Myeloma Patients: A Randomized, Controlled Trial

Stem cell factor (SCF) has been shown to synergize with filgrastim to mobilize CD34+ cells into the peripheral blood. To determine if addition of SCF to chemotherapy and filgrastim reduces the number of leukaphereses required to achieve a target yield of 5 × 106 CD34+ cells/kg, 102 patients with multiple myeloma were randomized to receive mobilization chemotherapy with cyclophosphamide (4 g/m2) and either SCF (20 μg/kg/d) combined with filgrastim (5 μg/kg/d) or filgrastim alone (5 μg/kg/d), administered daily until leukaphereses were completed. After collection, patients were treated with myeloablative therapy supported by autologous peripheral blood progenitor cell (PBPC) infusion and filgrastim (5 μg/kg/d). There was a significant difference between the treatment groups in the number of leukaphereses required to collect 5 × 106 CD34+ cells/kg (median of 1 v 2 for SCF + filgrastim and filgrastim alone, respectively, P = .008). Patients receiving the combination of SCF plus filgrastim had a 3-fold greater chance of reaching 5 × 106 CD34+ cells/kg in a single leukapheresis compared with patients mobilized with filgrastim alone. The median CD34+ cell yield was significantly increased for the SCF group in the first leukapheresis (11.3 v 4.0 × 106/kg, P = .003) and all leukaphereses (12.4v 8.2 × 106/kg, P = .007). Total colony-forming unit–granulocyte-macrophage (CFU-GM) and mononuclear cell counts were also significantly higher in the SCF group in the first leukapheresis and in all leukaphereses. As expected for patients mobilized to an optimal CD34+ cell yield, the time to engraftment was similar between the 2 treatment groups. Cells mobilized with the combination of SCF plus filgrastim were thus considered effective and safe for achieving rapid engraftment. Treatment with SCF plus filgrastim was well tolerated, with mild to moderate injection site reactions being the most frequently reported adverse events. There were no serious allergic-like reactions to SCF. The addition of SCF to filgrastim after cyclophosphamide for PBPC mobilization resulted in a significant increase in CD34+cell yield and a concomitant reduction in the number of leukaphereses required to collect an optimal harvest of 5 × 106CD34+ cells/kg.

Peripheral blood progenitor cell (PBPC) counts during steady-state haemopoiesis enable the estimation of the yield of mobilized PBPC after granulocyte colony-stimulating factor supported cytotoxic chemotherapy: an update on 100 patients.

Peripheral blood progenitor cells (PBPC) can be mobilized using chemotherapy and granulocyte colony-stimulating factor (G-CSF). We and others previously reported a correlation of steady-state PBPC counts and the PBPC yield during mobilization in a small group of patients. Here we present data on 100 patients (patients: 25 non-Hodgkin's lymphoma (NHL), five Hodgkin's disease, 35 multiple myeloma (MM), 35 solid tumour) which enabled a detailed analysis of determinants of steady-state PBPC levels and of mobilization efficiency in patient subgroups. Previous irradiation (P = 0.0034) or previous chemotherapy in patients with haematological malignancies (P = 0.0062) led to a depletion of steady-state PB CD34+ cells. A correlation analysis showed steady-state PB CD34+ cells (all patients: r = 0.52, P < 0.0001; NHL patients, r = 0.69, P = 0.0003; MM patients: r = 0.66, P = 0.0001) and PB colony-forming cells can reliably assess the CD34+ cell yield in mobilized PB. In patients with solid tumour a similar trend was observed in mobilization after the first chemotherapy cycle (r = 0.51, P = 0.05) but not if mobilization occurred after the second or further cycle of a sequential dose-intensified G-CSF-supported chemotherapy regimen, when premobilization CD34+ counts were 18-fold elevated (P = 0.004). When the patients with MM (r = 0.63, P = 0.0008) or with NHL (r = 0.65, P = 0.006) were analysed separately, a highly significant correlation of the steady-state PB CD34+ cell count to the mean leukapheresis CD34+ cell yield was found, whereas no correlation was observed for patients with a solid tumour. For patients with haematological malignancies estimates could be calculated which, at a specific steady-state PB CD34+ cell count, could predict with a 95% probability a defined minimum progenitor cell yield. These results enable recognition of patients who mobilize PBPC poorly and may assist selection of patients for novel mobilization regimens.

Technical aspects and performance in collecting peripheral blood progenitor cells.

The combination of effective mobilization protocols and efficient use of apheresis systems has led to a rapid growth of peripheral blood progenitor cell (PBPC) transplantation. The specifications for these procedures are changing towards more automated systems for standard collections to minimize operator interaction and to collect PBPC efficiently from donors and patients and also to reduce the collection of undesired cells such as polymorphonuclear cells and platelets using functionally closed, sterile environments for collection, in keeping with good manufacturing practice guidelines. The increasing need for pediatric procedures requires apheresis systems that run efficiently at low flow rates. It is also desirable to have a low extracorporeal volume. Technical considerations related to PBPC harvesting should include strategies facilitating more efficient collection such as large-volume leukapheresis, which is able to increase the PBPC yield. The most common complication related to apheresis is catheter occlusion, and care should be taken to prevent thrombosis and maintain vascular access. However, refinement and improvement of collection techniques continue to add to the armamentarium of current approaches for cancer and nonmalignant conditions and will enable the development of new strategies.

The COBE Spectra cell separator is more effective than the Haemonetics MCS‐3P cell separator for peripheral blood progenitor cell harvest after mobilization with cyclophosphamide and filgrastim

Peripheral blood is rapidly replacing bone marrow as a source of hematopoietic progenitor cells for autologous transplantation. The advantages of peripheral blood progenitor cell transplantation are enhanced by the ability to collect sufficient progenitor cells to ensure rapid neutrophil and platelet recovery in a single procedure on some cell separators. A prospective randomized study was undertaken to compare peripheral blood progenitor cell yields from two cell separators (MCS-3P, Haemonetics and Spectra, COBE). Fifteen consecutive patients were mobilized with cyclophosphamide 2 g per m2 (Day 0) and filgrastim 10 micrograms per kg (Days 1-11). Consecutive collections (Day 10, Day 11) were performed with each machine once: patients were randomly assigned to either machine for the initial collection. Collection time was longer on the MCS-3P (p = 0.001), and the volume processed was greater with the Spectra (p < 0.0001). Despite similar nucleated cell yield (p = 0.62), the yield of CD34+ cells (p = 0.001) and colony-forming units-granulocytic-monocytic (p = 0.0001) was significantly higher with the Spectra. The yield of nucleated cells per unit of blood volume processed was higher for the MCS-3P (p = 0.0007), while the CD34+ cell yield (p = 1) and colony-forming units-granulocytic-monocytic yield (p = 1) per unit of blood volume processed were similar for the two machines. The collection of CD34+ cells at levels > 2 x 10(6) per kg (p = 0.063), 5 x 10(6) per kg (p = 0.031), and colony-forming units-granulocytic-monocytic > 1 x 10(5) per kg (p = 0.25) after a single collection was superior for the Spectra. The yield of progenitor cells after collection on the Spectra was superior to that achieved with the MCS-3P, because of the larger volume of blood processed per procedure. This would permit more patients to undergo only one collection.

Preapheresis peripheral blood CD34+ mononuclear cell counts as predictors of progenitor cell yield.

Peripheral blood progenitor cells, harvested by apheresis after mobilization, provide rapid hematologic recovery after high-dose chemotherapy. However, because harvesting these cells is expensive and time-consuming, there has been much interest in optimizing collection protocols. An investigation was made to determine whether, in this clinical setting, peripheral blood progenitor cell yields may be predicted from preapheresis progenitor cell counts, allowing the length of each procedure to be "fine tuned" to achieve specific target goals. Preapheresis peripheral blood CD34+ cell and total colony-forming cell counts were assessed before 78 peripheral blood progenitor cell collections from 13 consecutive patients were performed. Preapheresis counts were correlated with actual progenitor cell yields. Factors affecting this correlation were analyzed. With the use of linear regression analysis preapheresis progenitor cell counts were found to correlate significantly but weakly with actual yields per kg of body weight per liter of blood processed (CD34+ cells: r = 0.43; colony-forming cells: r = 0.56). Further analysis revealed two possible causes: 1) circulating progenitor cell concentrations fluctuate widely during harvest, which implies that preapheresis counts are not representative of actual concentrations during apheresis, and 2) the efficiency with which apheresis machines extract mononuclear cells varies greatly between procedures. Preapheresis CD34+ and colony-forming cell counts correlated poorly with subsequent yields in this clinical setting, which suggests that it is not practical to use such counts to predict with certainty the length of apheresis needed to achieve a target yield.

Do Steady-State Peripheral Blood Progenitor Cell (PBPC) Counts Predict the Yield of PBPC Mobilized by Filgrastim Alone?

Do Steady-State Peripheral Blood Progenitor Cell (PBPC) Counts Predict the Yield of PBPC Mobilized by Filgrastim Alone?

Patient Characteristics Associated With Successful Mobilizing and Autografting of Peripheral Blood Progenitor Cells in Malignant Lymphoma

For patients with advanced-stage or poor-prognosis malignant lymphoma, high-dose therapy with peripheral blood progenitor cell (PBPC) support may become a first-line treatment. The duration of severe cytopenia in this setting is inversely related to the number of PBPCs autografted. In a retrospective analysis, we therefore looked for factors influencing the yield of PBPCs in 61 patients (16 with high-grade and 29 with low-/intermediate-grade non-Hodgkin's lymphoma [NHL], and 16 with Hodgkin's disease) who received cytotoxic chemotherapy and filgrastim (R-metHuG-CSF, 300 micrograms/d; median, 4.2 micrograms/kg/d; range, 2.7 to 6.6 micrograms/kg/d; subcutaneously). Sixteen patients had active disease, while 45 were in partial remission (PR) or complete remission (CR) after conventional therapy. A median of three leukaphereses (range, one to 10) resulted in a median of 5.7 x 10(6) CD34+ cells/kg (range, 0.03 to 31.1 x 10(6)). Previous cytotoxic chemotherapy and irradiation adversely affected the yield of CD34+ cells. Each cycle of chemotherapy is associated with an average decrease of 0.2 x 10(6) CD34+ cells/kg per leukapheresis in nonirradiated patients, while large-field radiotherapy reduces the collection efficiency by an average of 1.8 x 10(6)/kg CD34+ cells. The collection efficiency was also significantly lower in patients with Hodgkin's disease. However, except for one, all had been previously irradiated. In contrast, age, sex, disease status, bone marrow involvement during mobilization, and the time since the last chemotherapy or radiotherapy were not significantly related to the collection efficiency. Following high-dose conditioning therapy, 42 patients were autografted with filgrastim-mobilized PBPCs. Hematological recovery (neutrophils > or = 0.5 x 10(9)/L and an unsupported platelet count > or = 20 x 10(9)/L) within 2 weeks was observed in patients autografted with > or = 2.5 x 10(6) CD34+ cells/kg. In seven patients, the quantity of CD34+ cells reinfused was below this threshold. They required a median of 17 days (range, 11 to 34) and 31 days (range, 13 to 141) for neutrophil and platelet recovery, respectively. If autografting with PBPCs in malignant lymphoma with poor prognosis is being considered, mobilization and harvesting should be planned early after initial diagnosis to avoid exhaustion of hematopoiesis by cumulative toxicity.

Patient characteristics associated with successful mobilizing and autografting of peripheral blood progenitor cells in malignant lymphoma

For patients with advanced-stage or poor-prognosis malignant lymphoma, high-dose therapy with peripheral blood progenitor cell (PBPC) support may become a first-line treatment. The duration of severe cytopenia in this setting is inversely related to the number of PBPCs autografted. In a retrospective analysis, we therefore looked for factors influencing the yield of PBPCs in 61 patients (16 with high-grade and 29 with low-/intermediate-grade non-Hodgkin's lymphoma [NHL], and 16 with Hodgkin's disease) who received cytotoxic chemotherapy and filgrastim (R-metHuG-CSF, 300 micrograms/d; median, 4.2 micrograms/kg/d; range, 2.7 to 6.6 micrograms/kg/d; subcutaneously). Sixteen patients had active disease, while 45 were in partial remission (PR) or complete remission (CR) after conventional therapy. A median of three leukaphereses (range, one to 10) resulted in a median of 5.7 x 10(6) CD34+ cells/kg (range, 0.03 to 31.1 x 10(6)). Previous cytotoxic chemotherapy and irradiation adversely affected the yield of CD34+ cells. Each cycle of chemotherapy is associated with an average decrease of 0.2 x 10(6) CD34+ cells/kg per leukapheresis in nonirradiated patients, while large-field radiotherapy reduces the collection efficiency by an average of 1.8 x 10(6)/kg CD34+ cells. The collection efficiency was also significantly lower in patients with Hodgkin's disease. However, except for one, all had been previously irradiated. In contrast, age, sex, disease status, bone marrow involvement during mobilization, and the time since the last chemotherapy or radiotherapy were not significantly related to the collection efficiency. Following high-dose conditioning therapy, 42 patients were autografted with filgrastim-mobilized PBPCs. Hematological recovery (neutrophils &gt; or = 0.5 x 10(9)/L and an unsupported platelet count &gt; or = 20 x 10(9)/L) within 2 weeks was observed in patients autografted with &gt; or = 2.5 x 10(6) CD34+ cells/kg. In seven patients, the quantity of CD34+ cells reinfused was below this threshold. They required a median of 17 days (range, 11 to 34) and 31 days (range, 13 to 141) for neutrophil and platelet recovery, respectively. If autografting with PBPCs in malignant lymphoma with poor prognosis is being considered, mobilization and harvesting should be planned early after initial diagnosis to avoid exhaustion of hematopoiesis by cumulative toxicity.