Efficacy of single-dose pegfilgrastim after chemotherapy for the mobilization of autologous peripheral blood stem cells in patients with malignant lymphoma or multiple myeloma

BACKGROUND: A single injection of pegfilgrastim has been shown to be equivalent to daily filgrastim in enhancing neutrophil recovery after chemotherapy, whereas the experiences with pegfilgrastim in mobilization of peripheral blood progenitor cells (PBPCs) are limited. STUDY DESIGN AND METHODS: Forty unselected patients with lymphoma or multiple myeloma were treated with different chemotherapy regimens followed by 6 mg of pegfilgrastim for mobilization of autologous PBPCs. Patients with an inadequate mobilization (blood CD34+ cells 相似文献   

Inverse relationship between patient peripheral blood CD34+ cell counts and collection efficiency for CD34+ cells in two automated leukapheresis systems

BACKGROUND: The purpose of this study was to analyze the CD34 cell collection efficiency (CE) of automated leukapheresis protocols of two blood cell separators (Spectra, COBE [AutoPBSC protocol] and AS104, Fresenius [PBSC-Lym, protocol]) for peripheral blood progenitor cell (PBPC) harvest in patients with malignant diseases. STUDY DESIGN AND METHODS: PBPCs were collected by the Spectra AutoPBSC protocol in 95 patients (123 collections) and the AS104 PBSC-Lym protocol in 87 patients (115 harvests). Patients underwent a median of one (range, 1-4) conventional-volume apheresis procedure of 10.8 L (9.0-13.9) to obtain a target cell dose of > or =2.5 x 10(6) CD34+ cells per kg. RESULTS: The median overall CD34 CE was significantly better on the AS104 than on the Spectra: 55.8 percent versus 42.4 percent (p = 0.000). This was also true below (59.2% vs. 50.1%; p = 0.022) and above (51.2% vs. 41.3%; p = 0.001) the preleukapheresis threshold of 40 CD34+ cells per microL needed to collect a single-apheresis autograft. However, at > or =40 circulating CD34+ cells per microL, both cell separators achieved the target of > or =2.5 x 10(6) CD34+ cells per kg. The CD34 CE dropped significantly, from 59.2 percent at <40 cells per microL to 51.2 percent at > or =40 cells per microL on the AS104 (p = 0.017) and from 50.1 percent to 41.3 percent on the Spectra (p = 0.033). CONCLUSION: Whereas the CD34 CE was significantly different with the AS104 and the Spectra, the CD34 CE of both machines correlated inversely with peripheral blood CD34+ cell counts, showing a significant decline with increasing numbers of circulating CD34+ cells. Nevertheless, at > or 40 preapheresis CD34+ cells per microL, sufficient hematopoietic autografts of > or =2.5 x 10(6) CD34+ cells per kg were harvested by a single conventional-volume (11 L) leukapheresis on both cell separators.     

Initiation of peripheral blood progenitor cell harvest based on peripheral blood hematopoietic progenitor cell counts enumerated by the Sysmex SE9000

BACKGROUND: The most reliable index for timing peripheral blood progenitor cell (PBPC) collection following mobilization is still to be determined. The techniques to enumerate peripheral blood (PB) CD34+ cells are expensive and time-consuming. The SE9000 (Sysmex) provides an estimate of immature cells, called hematopoietic progenitor cells (HPCs). The aim of this study was to prospectively evaluate the efficacy of PB HPC levels for timing PBPC harvest. STUDY DESIGN AND METHODS: Thirty-five patients (15 non-Hodgkin's lymphoma and 20 multiple myeloma) were enrolled. PB HPCs and harvested CD34+ cells were counted with the SE9000 and flow cytometry, respectively. Circulating HPCs were monitored daily. PBPC harvest was initiated when HPC levels reached at least 5 per mm(3). RESULTS: HPC levels reached 5 per mm(3) or more on Median Day 12 (range, days 9 to 16) of mobilizing chemotherapy. The median number of CD34+ cells collected per patient was 19.40 x 10(6) per kg (range, 1.94 x 10(6)-52.55 x 10(6) per kg). Both successful and optimal harvest was achieved in 97 percent of patients. PBPCs were successfully harvested in 25 patients (71%) in one session. An optimal harvest in a single session was attained in 16 patients (46%). CONCLUSION: This might be the first prospective study showing the PB HPC level for timing PBPC harvest.     

CD34+ cell mobilization for allogeneic progenitor cell transplantation: efficacy of a short course of G-CSF

BACKGROUND: G-CSF-mobilized PBPCs are considered the richest source of HPCs for both autologous and allogeneic transplantation, but, despite their wide use, the best dose and schedule for G-CSF administration have not been definitively established. STUDY DESIGN AND METHODS: With a target of collecting from the peripheral blood > or = 4 x 10(6) CD34+ cells per kg of body weight of the recipient, the short-course administration of glycosylated G-CSF (gly-G-CSF) in 30 healthy donors for an allogeneic transplantation was investigated. Gly-G-CSF was given subcutaneously at a dose of 10 microg per kg per day in two divided doses over 3 days and was followed by a leukapheresis (on the 4th day) 12 hours after the last dose. RESULTS: A median of 53.5 circulating CD34+ cells per microL (range, 19-190) was found in the 30 donors on the day of first leukapheresis, which allowed a median CD34+ cell collection of 6.0 x 10(6) per kg of body weight of the donor and 6.5 x 10(6) per kg of body weight of the recipient. In 25 (83%) of 30 donors, a single procedure was sufficient to collect the target CD34+ cells, while in the other 5, two leukapheresis procedures were required. Hematologic reconstitution was observed in all patients at a median of 14 days (range, 10-23) for neutrophils and 14.5 days (range, 11-46) for platelets. With a median infusion of 3.9 x 10(8) CD3+ T-lymphocytes per kg of body weight of the recipient (range, 1.3-7.8), acute and chronic GVHD occurred in 13 (43%) of 30 and 15 (60%) of 25 evaluable patients, respectively. After a median follow-up of 337 days from transplant, 22 (73%) of 30 patients are alive in complete remission. CONCLUSION: A schedule consisting of 3-day administration of gly-G-CSF followed by a single leukapheresis can be proposed and widely accepted by healthy donors, as 84 percent of them reach the target in the estimated time with a reduced drug exposure. The cost of the procedure is reduced, in terms of both the growth factor administration and the number of leukapheresis procedures. The search for the optimum methods of donor management may improve the acceptability of this procedure and increase the number of allogeneic transplantations from PBPCs.     

PBPC mobilization with paclitaxel, ifosfamide, and G-CSF with or without amifostine: results of a prospective randomized trial

BACKGROUND: The impact of amifostine on PBPC mobilization with paclitaxel and ifosfamide plus G-CSF was assessed. STUDY DESIGN AND METHODS: Forty patients with a median age of 34 years (range, 19-53) who had germ cell tumor were evaluated for high-dose chemotherapy. Patients were randomly assigned to receive either a single 500-mg dose of amifostine (Group A, n = 20) or no amifostine (Group B, n = 20) before mobilization chemotherapy with paclitaxel (175 mg/m(2)) given over 3 hours and ifosfamide (5 g/m(2)) given over 24 hours (TI) on Day 1. G-CSF at 10 microg per kg per day was given subsequent to TI with or without amifostine from Day 3 until the end of leukapheresis procedures. RESULTS: In 2 (10%) of 20 patients receiving amifostine and 3 (15%) of 20 patients not receiving it, no PBPC separation was performed because of mobilization failure. No significant differences were observed in the study arms with regard to the time from chemotherapy until first PBPC collection or the number of apheresis procedures needed to harvest more than 2.5 x 10(6) CD34+ cells per kg. Furthermore, leukapheresis procedures yielded comparable doses of CD34+ cells per kg (3.4 x 10(6) vs. 3.6 x 10(6); p = 0.82), MNCs per kg (2.7 x 10(8) vs. 2.6 x 10(8); p = 0.18), and CFU-GM per kg (15.9 x 10(4) vs. 19.3 x 10(4); p = 0.20). Patients in Group A had higher numbers of circulating CD34+ cells on Day 10 (103.0/microL vs. 46.8/microL; p = 0.10) and on Day 11 (63.0/microL vs.14.3/microL; p = 0.04) than did patients in Group B. CONCLUSION: Administration of a single dose of amifostine before chemotherapy with TI mobilized higher numbers of CD34 cells in the circulation, but did not enhance the overall collection efficiency in the present trial.     

Factors affecting the efficacy of peripheral blood progenitor cells collections by large-volume leukaphereses with standardized processing volumes

BACKGROUND: Peripheral blood progenitor cell (PBPC) collections should be safe and efficient. Therefore, the influence and risk factors in large-volume leukaphereses (LVL) with standardized blood volumes was investigated. STUDY DESIGN AND METHODS: In a total of 724 autologous LVL performed at our center, either 4x or 6x the patient's blood volume (PBV) was processed. The group with processing 4x the PBV showed a median of 31 circulating CD34+ cells per microL, and the group with processing 6x the PBV had a median of 13 CD34+ cells per microL before LVL. Individual clinical factors, laboratory factors, and apheresis run variables influencing the yields of PBPCs were retrospectively analyzed. Furthermore, the changes of laboratory variables and adverse effects during LVL were investigated. RESULTS: Multivariate analysis identified "age,"circulating CD34+ cells," and "percentage of mononuclear cells" as only factors influencing the yields of PBPCs. Altogether, processing 6x versus 4x the PBV did not result in significantly higher yields of CD34+ cells for the total group, but requested PBPC yields were achieved more often after processing 6x the PBV in patients below 20 CD34+ cells per microL blood. Processing 6x versus 4x the PBV showed a significant difference for the decrease of platelets, but not for any other laboratory variable. Adverse effects were recorded in 4.97 percent of LVL without accumulation in one group. CONCLUSION: In particular, patients with low amounts of circulating CD34+ cells profited from enlarged LVL demonstrating higher PBPC yields but comparable rates of adverse effects.     

Kinetics of PBPC mobilization by cyclophosphamide, as compared with that by epirubicin/paclitaxel followed by G-CSF support: implications for optimal timing of PBPC harvest

BACKGROUND: Limited information is available on the mobilization kinetics of autologous PBPCs after induction with various chemotherapy regimens. With PBPC mobilization in patients with breast cancer used as a model for chemotherapy-induced PBPC recruitment, the kinetics of progenitor cells mobilized either with cyclophosphamide (CY) or epirubicin/paclitaxel (EPI-TAX) followed by the administration of G-CSF was compared. STUDY DESIGN AND METHODS: The study included a total of 86 patients with breast cancer (stage II-IV) receiving either CY (n = 39) or EPI-TAX (n = 47), both followed by G-CSF support. The progenitor cell content in peripheral blood and apheresis components was monitored by flow cytometric enumeration of CD34+ cells. PBPC collection was started when the threshold of >20 x 10(6) CD34+ cells per L of peripheral blood was reached. RESULTS: The PBPC collection was begun a median of 9 days after the administration of EPI-TAX followed by G-CSF support, as compared to a median of 13 days after mobilization with CY plus G-CSF. After treatment with CY, the total numbers of PBPCs peaked on Day 1 of apheresis, and they rapidly declined thereafter. In contrast, treatment with EPI-TAX followed by G-CSF administration led to a steady mobilization of CD34+ cells during leukapheresis. The difference in the mobilization patterns with CY and EPI-TAX resulted in a greater yield of CD34+ cells per L of processed blood volume. Compared to EPI-TAX, mobilization with CY required the overall processing of 30 percent less whole-blood volume to reach the target yield of > or = 10 x 10(6) CD34+ cells per kg of body weight. After a median of three apheresis procedures, however, both CY+G-CSF and EPI-TAX+G-CSF were equally effective in obtaining this target yield. CONCLUSION: These results imply that specific PBPC mobilization as part of a given chemotherapy regimen should be taken into consideration before the planning of a PBPC harvest.     

Large-volume leukapheresis yields more viable CD34+ cells and colony-forming units than normal-volume leukapheresis, especially in patients who mobilize low numbers of CD34+ cells

BACKGROUND: Large-volume leukapheresis (LVL) differs from normal-volume leukapheresis (NVL) by increased blood flow and altered anticoagulation regimen. LVL is now regarded as a safe procedure for collection of peripheral blood progenitor cells (PBPCs), but it is not known whether the procedure will alter CD34+ cell quality or will be useful for patients who mobilize few CD34+ cells into peripheral blood. STUDY DESIGN AND METHODS: The results from 82 LVL and 125 NVL (4.0-5.3 and 2.7-3.5 times the patients' blood volumes processed, respectively) were retrospectively analyzed in altogether 112 consecutive patients with malignant diseases. RESULTS: The LVL yielded significantly more CD34+ cells (4.2 x 10(6) vs. 3.1 x 10(6)/kg, p = 0.006, all patients; and 1.8 x 10(6) vs. 1.3 x 10(6)/kg, p = 0.004, bad mobilizers) and significantly higher colony-forming units (77 x 10(4) vs. 33 x 10(4)/kg; all patients and 33 x 10(4) vs. 20 x 10(4)/kg, p < 0.001, both groups). Significantly fewer leukapheresis procedures were required to obtain 2 x 10(6) CD34+ cells per kg (one vs. two, p = 0.001, all patients; and two vs. three, p = 0.009, bad mobilizers). No significant differences in CD34+ cell viability and time to hematologic recovery were observed between the patients who received PBPCs harvested by NVL and LVL. CONCLUSION: Although a median platelet loss of 36 percent can be expected, LVL can be recommended as the standard apheresis method for PBPC collections in patients with malignant diseases. LVL is particularly useful in patients who mobilize a low number of CD34+ cells into the peripheral blood.     

The number of CD34(+) cells in peripheral blood as a predictor of the CD34(+) yield in patients going to autologous stem cell transplantation

The number of CD34(+) cells in peripheral blood (PB) is a guide to the optimal timing to harvest peripheral blood progenitor cells (PBPC). The objective was to determine the number of CD34(+) cells in PB that allows achieving a final apheresis product containing > or =1.5 x 10(6) CD34(+) cells/kg, performing up to three aphereses. Between March 1999 and August 2003, patients with hematological and solid malignancies who underwent leukapheresis for autologous bone marrow transplantation were prospectively evaluated. Seventy-two aphereses in 48 patients were performed (mean 1.45 per patient; range 1-3). PBPC were mobilized with cyclophosphamide plus recombinant human granulocyte-colony stimulating factor (G-CSF) (n = 40), other chemotherapy drugs plus G-CSF (n = 7), or G-CSF alone (n = 1). We found a strong correlation between the CD34(+) cells count in peripheral blood and the CD34(+) cells yielded (r = 0.903; P < 0.0001). Using receiver-operating characteristic (ROC) curves, the minimum number of CD34(+) cells in PB to obtain > or =1.5 x 10(6)/kg in the first apheresis was 16.48 cells/microL (sensitivity 100%; specificity 95%). The best cut-off point necessary to obtain the same target in the final harvest was 15.48 cells/microL, performing up to three aphereses (sensitivity 89%; specificity 100%). In our experience, > or =15 CD34(+) cells/microL is the best predictor to begin the apheresis procedure. Based on this threshold level, it is possible to achieve at least 1.5 x 10(6)/kg CD34(+) cells in the graft with < or =3 collections.     

Non-cryopreserved peripheral blood progenitor cells collected by a single very large-volume leukapheresis: a simplified and effective procedure for support of high-dose chemotherapy

High-dose chemotherapy with autologous peripheral blood progenitor cell (PBPC) support has become a widely used treatment strategy. In order to simplify the procedure, a single very large-volume leukapheresis programme combined with short-term refrigerated storage of the PBPC was developed. Seventy-two patients suffering from various relatively chemosensitive malignancies received high-dose chemotherapy, consisting of agents with short in vivo half-lives and 24 to 48 hours later, the refrigerated PBPC were reinfused. A single very large-volume apheresis was sufficient to obtain at least 2 x 10(6)/kg CD34+ cells in 58 patients (81%), and 63% had at least 2.5 x 10(6) CD34+ cells/kg. Only two patients (3%) were transplanted with less than 1 x 10(6) CD34+ cells/kg. In three patients (4%) leukapheresis was repeated because of insufficient number of PBPC. The median CD34+ cell count was 3 x 10(6)/kg. A median of 38.5 L blood (range, 21 to 59) was processed, which accounted for a median of 9 x patient's total blood volume. Very large-volume leukapharesis was well tolerated with symptomatic hypocalcemia being the most common (18%) side-effect. The median time to neutrophils >1.5 x 10(9)/L, and to self-supporting platelet count >25 x 10(9)/L, was 10 and 12 days after reinfusion of PBPC graft, respectively. There were no treatment-related deaths. Our results indicate that this simplified approach of PBPC transplantation can be associated with prompt hematologic recovery in most patients and that it can be useful in settings where facilities are limited or for certain diseases where conditioning regimens with short half-life are appropriate. J. Clin. Apheresis, 15:236-241, 2000.     

The absolute number of peripheral blood CD34+ cells predicts a timing for apheresis and progenitor cell yield in patients with hematologic malignancies and solid tumors

Retrospective analysis was conducted in 51 autologous peripheral blood progenitor cell (PBPC) collections using the Spectra AutoPBSC System from patients with hematologic malignancies and solid tumors to study the predictive value of CD34+ cell counts in the peripheral blood for the yield of CD34+ cells in the apheresis product. The correlation coefficients for CD34+ cells microL(-1) of peripheral blood with CD34+ cell yield (x 10(6) kg(-1) of body weight and x 10(5) kg(-1) of body weight L(-1) of blood processed) were 0.903 and 0.778 (n=51 collections), respectively. Products collected from patients with CD34+ cell counts below 15 microL(-1) in the peripheral blood contained a median of 0.49 x 10(6) CD34+ cells kg(-1) (range: 0.05-2.55), whereas those with CD34+ cell counts more than 15 microL(-1) contained a median of 3.72 x 10(6) CD34+ cells kg(-1) (range: 1.06-37.57). From these results, a number of at least 15 CD34+ cells microL(-1) in the peripheral blood ensured a minimum yield of 1 x 10(6) CD34+ cells kg(-1) as obtained by a single apheresis procedure. The number of CD34+ cells in the peripheral blood can be used as a good predictor for timing of apheresis and estimating PBPC yield. With regard to our results, apheresis with a possibly poor efficiency should be avoided because the collection procedure is time-consuming and expensive.     

Large-volume leukapheresis for peripheral blood progenitor cell collection in low body weight pediatric patients: a single center experience.

Peripheral blood progenitor cells (PBPC) have became the preferred source of stem cells for autologous transplantation because of easier accessibility, rapid engraftment, and lower tumor cell contamination. In pediatric patients is very important to optimize peripheral blood stem cells (PBSC) harvesting to obtain a sufficient number of cells with a reduced number of leukapheresis. In this study we prospectively analyzed data on 43 large volume leukapheresis (LVL) from 20 consecutive low body weight pediatric patients with various malignancies. Patients' mean body weight was 16.6 kg (range, 8.9-32.0 kg), and the median age was 4 years (range, 1-10 y ears). Instead of saline, it was used irradiated and leukoreduced red blood cell (RBC) units to prime the machine in 15 patients weighting 25 kg or less. The median number of LVL was 2 (range, 1-4) and a mean of 5.2 patient's blood volume was processed per session lasting 165 min (range, 118-239). The mean number of CD34+ cells, one day before leukapheresis was 49 mm(-3) (range, 9-219). The PBPC collection yielded 24.7 x 10(8) total nucleated cells/kg (range, 6.2-74.0), 10.7 x 10(6) kg(-1) CD34+ cells (range, 3.6-53.7); 49.8 x 10(4) CFU-GM/kg (range, 6.4-198.1), and 65.6 x 10(4) BFU-E/kg (range, 7.6-198.1). The platelet count decreased significantly after each procedure 39.8 +/- 9.1 x 10(9) mm(-3) (range, 18.000-76.000) (p < 0.001). In conclusion, our data show that LVL for collection of PBPC in low weight pediatric patients is a safe and efficient procedure, but it may expose the patient to the risk of thrombocytopenia.     

Phase III randomized study comparing 5 or 10 microg per kg per day of filgrastim for mobilization of peripheral blood progenitor cells with chemotherapy,followed by intensification and autologous transplantation in patients with nonmyeloid malignancies

BACKGROUND: It is not known whether increasing the dose of filgrastim after mobilizing chemotherapy improves collection of peripheral blood progenitor cells (PBPC) and leads to faster hematopoietic engraftment after autologous transplantation. STUDY DESIGN AND METHODS: A randomized, open-label, multicenter trial was carried out in patients with breast cancer, multiple myeloma, and lymphoma, in which patients were randomized to receive 5 or 10 microg per kg per day of filgrastim after standard chemotherapy to mobilize PBPCs. After high-dose chemotherapy, the components from the first two leukapheresis procedures were returned, and all patients received 5 microg per kg day of filgrastim after transplantation. RESULTS: A total of 131 patients were randomized, of whom 128 were mobilized (Group A, 5 microg/kg, n = 66; Group B, 10 microg/kg, n = 62) and 112 were transplanted. Only six patients were not transplanted because of insufficient CD34+ cell numbers. The median number of CD34+ cells collected in the first two leukapheresis procedures tended to be higher in Group B than in Group A (12.0 vs. 7.2 x 10(6)/kg, NS), but after transplantation there was no significant difference in median times to platelet (9 days in both groups) or neutrophil (8 days in both groups) engraftment or the number of platelet transfusions (three in both groups). A subsequent subgroup analysis separating patients transplanted after first- or second-line chemotherapy also showed no measurable impact of filgrastim dose on the median CD34+ cell yield or on platelet engraftment in either subgroup. CONCLUSION: PBPC mobilization with chemotherapy and 5 microg per kg of filgrastim is very efficient, and 10 microg per kg of filgrastim does not provide additional clinical benefit.     

In vitro collection and posttransfusion engraftment characteristics of MNCs obtained by using a new separator for autologous PBPC transplantation

BACKGROUND: A clinical study was performed to evaluate the peripheral blood progenitor cell (PBPC) collection, transfusion, and engraftment characteristics associated with use of a blood cell separator (Amicus, Baxter Healthcare). STUDY DESIGN AND METHODS: Oncology patients (n = 31) scheduled for an autologous PBPC transplant following myeloablative therapy were studied. PBPCs were mobilized by a variety of chemotherapeutic regimens and the use of G-CSF. As no prior studies evaluated whether PBPCs collected on the Amicus separator would be viable after transfusion, to ensure patient safety, PBPCs were first collected on another cell separator (CS-3000 Plus, Baxter) and stored as backup. The day after the CS-3000 Plus collections were completed, PBPC collections intended for transfusion were performed using the Amicus instrument. For each transplant, >2.5 x 10(6) CD34+ PBPCs per kg of body weight were transfused. RESULTS: Clinical data collected on the donors immediately before and after PBPC collection with the Amicus device were comparable to donor data similarly obtained for the CS-3000 Plus collections. While the number of CD34+ cells and the RBC volume in the collected products were equivalent for the two devices, the platelet content of the Amicus collections was significantly lower than that of the CS-3000 Plus collections (4.35 x 10(10) platelets/bag vs. 6.61 x 10(10) platelets/bag, p<0.05). Collection efficiencies for CD34+ cells were 64 +/- 23 percent for the Amicus device and 43 +/- 14 percent for the CS-3000 Plus device (p<0.05). The mean time to engraftment for cells collected via the Amicus device was 8.7 +/- 0.7 days for >500 PMNs per microL and 9.7 +/- 1.5 days to attain a platelet count of >20,000 per microL-equivalent to data in the literature. No CS-3000 Plus backup cells were transfused and no serious adverse events attributable to the Amicus device were encountered. CONCLUSIONS: The mean Amicus CD34+ cell collection efficiency was better (p<0.05) than that of the CS-3000 Plus collection. Short-term engraftment was durable. The PBPCs collected with the Amicus separator are safe and effective for use for autologous transplant patients requiring PBPC rescue from high-dose myeloablative chemotherapy.     

High platelet contamination in progenitor cell concentrates results in significantly lower CD34+ yield after immunoselection

BACKGROUND: Selection of CD34+ cells by specific immunoselection leads to a significant loss of those cells. The factors influencing the yield and purity are not well identified. The results of CD34+ selection from peripheral blood progenitor cells (PBPCs) with high and low platelet contamination that are harvested with two different cell separators are reported. STUDY DESIGN AND METHODS: A progenitor cell concentrator (Ceprate SC, CellPro) was used to select CD34+ cells from 41 PBPC concentrates from 23 consecutive patients with relapsed non-Hodgkin's lymphoma (n = 3), breast cancer (n = 17), and multiple myeloma (n = 3). PBPC collection was performed by using two cell separators (CS3000 Plus, Fenwal: Group A, n = 11; and Spectra, COBE: Group B, n = 9). To reduce platelet contamination in the Spectra PBPC concentrates, an additional low-speed centrifugation was performed before CD34+ cell selection (Group C, n = 3). Leukapheresis components were stored overnight at 4 degrees C and combined with the next day's collection before the CD34+ selection procedure in 19 patients. RESULTS: A median of 1.5 leukapheresis procedures per patient were performed. Pooled PBPC concentrates showed no statistical difference in median numbers of white cells and CD34+ cells in Groups A and B: 3.2 (0.8-9.2) versus 4.4 (1.6-8. 3) x 10(10) white cells per kg and 15.0 (4.7-24.0) versus 12.0 (5. 6-34.0) x 10(6) CD34+ cells per kg. Platelet contamination was significantly higher in Group B: 0.67 (0.15-2.4) versus 2.3 (0.5-7. 1) x 10(11) (p = 0.0273). After the selection process, there was a significantly greater loss of CD34+ cells in Group B than in Group A: 39.1 versus 63.2 percent (p = 0.0070), with a median purity of 78. 0 percent versus 81.0 percent. An additional low-speed centrifugation before CD34+ cell selection seemed to reduce CD34+ cell loss in Group C with 16.9, 31.9, and 37.5 percent, respectively. CONCLUSION: CD34+ cell selection from PBPC concentrates resulted in an increased loss of CD34+ cells in concentrates with a higher platelet content. To improve CD34+ yield, PBPC concentrates with an initially low platelet contamination should be used, or additional low-speed centrifugation should be performed.     

The timing of granulocyte–colony-stimulating factor administration after chemotherapy does not affect stem and progenitor cell apheresis yield: a retrospective study of 65 cases

BACKGROUND: The optimal time for postchemotherapy granulocyte-colony stimulating factor (G-CSF) administration before peripheral blood stem and progenitor cell (PBPC) collection is not well defined. The impact of G-CSF scheduling on the number of CD34+ cells collected by leukapheresis from 65 patients with malignant disease was studied retrospectively. STUDY DESIGN AND METHODS: Chemotherapy was performed on Days 1 and 2 and was followed by G-CSF to mobilize PBPCs. In Group 1, 30 patients received the first dose of G-CSF immediately after the end of chemotherapy, as commonly recommended. In Group 2, 35 patients received the first G-CSF dose after the end of chemotherapy (Days 7 or 8). RESULTS: No difference was observed between the two groups in white cell recovery and the median number of CD34+ cells harvested. The number of leukapheresis procedures necessary to obtain the minimal number of 3 x 10(6) CD34+ cells per kg was the same. The proportion of patients with a failure of PBPC collection was similar, and G-CSF consumption was reduced in Group 2 without increasing infectious risks. CONCLUSION: Early administration of G-CSF after chemotherapy appears not to be a prerequisite for satisfactory PBPC collection. This approach could allow significant savings in terms of medical cost. A randomized and prospective study would be necessary, however, to assess the validity of these conclusions.     

Evaluation of an algorithm based on peripheral blood hematopoietic progenitor cell and CD34+ cell concentrations to optimize peripheral blood progenitor cell collection by apheresis

BACKGROUND: Quantification of peripheral blood (PB) CD34+ cells is commonly used to plan peripheral blood progenitor cell (PBPC) collection but is time-consuming. Sysmex has developed a hematology analyzer that can quickly identify a population of immature hematopoietic cells (HPCs) according to cell size, cell density, and differential lysis resistance, which may indicate the presence of PBPCs in PB. This prospective study has evaluated the potential of such method to predict the PBPC mobilization. STUDY DESIGN AND METHODS: A total of 141 patients underwent PBPC mobilization. PB HPCs and PB CD34+ cells were simultaneously quantified with a hematology analyzer (SE2100, Sysmex) and flow cytometry, respectively. The number of blood volumes processed was then based on PB CD34+ cell concentration. RESULTS: The optimal PB HPC level able to predict a minimal level of 10 x 10(6) PB CD34+ cells per L was 5 x 10(6) per L with positive and negative predictive values of 0.93 and 0.36 percent, respectively. For this cutoff point, sensitivity and specificity were 0.81 and 0.65, respectively. The median number of blood volumes processed according to the PB CD34+ cell count allowed us to perform only one apheresis procedure for a majority of patients. CONCLUSION: PB HPC quantification is very useful to quickly determine the initiation of PBPC apheresis especially for patients with higher concentrations. For patients exhibiting a lower HPC count (<5 x 10(6)/L), other parameters such as a CD34 test may be needed. Such a policy associated with a length of apheresis adapted to the richness in the PB CD34+ cells allows for optimizing the organization of centers with an improvement in patient comfort and economical savings.     

Minimal number of circulating CD34+ cells to ensure successful leukapheresis and engraftment in autologous peripheral blood progenitor cell transplantation

BACKGROUND: The number of peripheral blood (PB) CD34+ cells has been widely used to monitor the timing of leukapheresis for autologous transplantation. However, no cutoff value for CD34+ cells in PB has been defined as a guideline for the identification of patients in whom the harvest would be effective and those in whom there was a high probability of failure. STUDY DESIGN AND METHODS: The present study investigated the best threshold of CD34+ cells in PB for successful harvesting and engraftment, using 263 PB samples with their corresponding leukapheresis components. In addition, that measure has been compared to other commonly used criteria such as the white cell count, the number of mononuclear cells, and the number of colony- forming units-granulocyte macrophage in PB. RESULTS : Time to engraftment of both granulocytes and platelets was significantly influenced by the number of CD34+ cells transfused, but all patients receiving > or = 0.75 × 10(6) CD34+ cells per kg achieved engraftment within a reasonable number of days (> 0.5 × 10(9)/L granulocytes by Day 11 and > 20 × 10(9)/L platelets by Day 13). A clear correlation between the number of CD34+ cells per microL in PB and of CD34+ cells per kg collected was found at each apheresis (r = 0.9, p < 0.0001). Moreover, the number of CD34+ cells per microL measured in PB the day the first leukapheresis was initiated displayed an excellent correlation with the total amount of CD34+ cells per kg finally collected (r = 0.81, p < 0.0001). On the basis of the regression curve obtained and the clinical engraftment results, it was found that the presence of > 5 CD34+ cells per microL in PB ensured a good yield from the harvest in 95 percent of patients and would avoid an unsuccessful harvest in 81 percent of cases. CONCLUSION: A dose of only 0.75 × 10(6) CD34+ cells per kg guarantees hematopoietic recovery within a reasonable number of days. To initiate a leukapheresis from which enough progenitor cells may confidently be obtained, a minimum of 5 CD34+ cells per microL in PB is required.     

The dose of granulocyte-colony-stimulating factor after chemopriming treatment does not influence apheresis yield of progenitor cells: a retrospective study of 91 cases

BACKGROUND: The optimal dose of post-chemotherapy granulocyte-colony-stimulating factor (G-CSF) administration before peripheral blood progenitor cell (PBPC) collection has not been determined as yet, although 5 microg per kg per day has been recommended as the standard dose. This study retrospectively analyzed the effect of G-CSF dose on peripheral blood CD34+ cell collection from 91 patients with hematologic malignancies. STUDY DESIGN AND METHODS: Various doses of G-CSF were administered after several chemotherapeutic PBPC mobilization regimens. According to the dose of G-CSF administered, patients were assigned to two groups. Group 1 included 46 patients who received a low dose of G-CSF (median, 3.6 [range, 2.8-4.6] microg/kg/day). Group 2 included 45 patients who received a standard G-CSF dose of 6.0 (5.5-8. 1) microg per kg per day. Patients in the two groups were matched for age, diagnosis, previous therapy, and chemotherapeutic PBPC mobilization regimens. RESULTS: No difference was observed in the median number of CD34+ cells harvested from each group.The number of leukapheresis procedures necessary to obtain a minimum of 3 x 10(6) CD34+ cells per kg was the same in both groups, and the percentage of patients who failed to achieve adequate PBPC collections was similar in the two groups. CONCLUSION: The administration of low-dose G-CSF after chemotherapy appears equivalent to administration of the standard dose in achieving satisfactory PBPC collection.This approach could allow significant savings in medical cost. A randomized and prospective study is necessary, however, to assess the validity of these conclusions.     

Harvesting peripheral blood progenitor cells from healthy donors with a short course of recombinant human granulocyte-colony-stimulating factor

A short-course administration of non-glycosylated granulocyte-colony-stimulating factor (G-CSF) was investigated in 68 healthy donors (HDs) in order to collect > or = 4 x 10(6) CD34+ cells per kilogram of recipient's body weight. G-CSF was given at 10 microg/kg per day administered in two divided doses for 3 days. Leukapheresis was scheduled on day 4, 12 h after the last dose of G-CSF. A median of 35.6 circulating CD34+ cells microL(-1) (range, 3.1-185) was found on the day of leukapheresis. This allowed a median collection of CD34+ cells of 4.2 x 10(6) per kilogram of recipient's weight (range, 1.0-17.4). One single procedure was sufficient to reach the target level of CD34+ cells in 36 (53%) of 68 donors; significant correlations were found between the number of CD34+ cells collected on day 4 and the patient's sex, body-weight and volume of blood processed. A retrospective analysis was made with a historical group of HDs collected on day 5. The day 5 schedule allowed a more consistent achievement of the target cell dose with one leukapheresis (P = 0.005) and resulted in the initial collection of a significantly larger number of CD34+ cells (P = 0.006).