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.     

PBPC collection techniques: standard versus large volume leukapheresis (LVL) in donors and in patients.

Transplantations of autologous and allogeneic peripheral blood progenitor cells (PBPC) are able to assure a complete hematopoietic and immunologic reconstitution in patients. PBPC are collected by leukapheresis technique after prior mobilization therapy, but procedures and results remain still highly variable and are poorly characterized. An optimum regimen for PBPC collections has not yet been recommended, but 2-3 total blood volumes (TBV) of the donor or patient are regarded as a standard. Another promising technique is large volume leukapheresis (LVL) with processing of 3-6 TBV of donor or patient. The aim of this paper is to find the most efficient and safe collection technique for an individual donor or patient and, consequently minimize the number of procedures required. Finding the optimal collection procedure would be helpful while considering which method would be preferred in an individual donor or patient with respect to the result of mobilization, health state and required yield of CD 34+ cells for transplantation. We evaluated the results in a total of 134 standard and LVL procedures, which were performed in 21 well mobilized donors (Group I), in 65 well mobilized patients (Group II), and in 14 weakly mobilized patients (Group III) with hemato-oncological diseases. A precollection concentration of CD 34+ cells in peripheral blood higher than 20 x 10(3)/mL was considered to be the criterion for efficient mobilization. Such levels of concentration indicating the start of PBPC collections could be easily reached in Group I of donors and Group II of well mobilized patients. Heavily pretreated patients at advanced stages of disease (Group III) did not respond to mobilization sufficiently and had a concentration of CD 34+ cells lower than 20x10(3)/mL. LVL technique made it possible to obtain higher numbers of CD 34+ cells than in the standard collection in well mobilized donors (Group I), well mobilized patients (Group II), and even in weakly mobilized patients in Group III. In donors and well mobilized patients (Group I and Group II) it was possible to collect sufficient amounts of CD 34+ cells for allogeneic or for autologous transplantation from one LVL collection. The median yield of CD 34+ cells from one LVL collection was 5.5 x 10(6)/kg b.w. in donors, and 6.0 x 10(6)/kg b.w. in well mobilized patients. Due to the linear dependence of the yield of collected CD 34+ cells on the concentration of CD 34+ cells in blood, it can be used as a simple prediction of the success of collection in Group II (correlation coefficient 0.93 for standard procedures, and correlation coefficient 0.88 for LVL). In Group III of weakly mobilized patients the standard collections were usually ineffective and the relationship between the yield of CD 34+ cells/kg in the product and the precollection concentration of CD 34+ cells was much less significant (correlation coefficient 0.56 for standard procedures and correlation coefficient 0.66 for LVL). The median of CD 34+ cells collected from one standard procedure was only 0.7 x 10(6)/kg but using LVL the median increased to 1.4 x 10(6)/kg. Our results prove that the yield of CD 34+ cells in the product can be enhanced by large volume leukapheresis (LVL). Based on the results obtained, we recommend LVL in all donors and patients who can tolerate it due to a greater chance of collecting higher yields of progenitor cells while minimizing adverse reactions. LVL procedures should also be preferred in weakly mobilized patients where it is not possible to collect sufficient amounts of CD 34+ cells for transplantation using the standard regime. In weakly mobilized patients LVL provides a greater chance to at least collect a minimum amount of CD 34+ cells necessary. LVL should be used in circumstances where extremely high doses of CD 34+ cells has to be prepared, e.g. planned "tandem" transplantations or manipulations with a graft in which a significant loss of cells is expected.     

Large-volume leukapheresis for collection of mononuclear cells for hematopoietic rescue in Hodgkin's disease

BACKGROUND: Peripheral blood mononuclear cells (MNCs) collected by leukapheresis contain hematopoietic stem and progenitor cells that provide autologous hematopoietic rescue after high-dose chemotherapy, an approach that offers a significant benefit to patients with recurrent Hodgkin's disease. However, patients with low MNC counts may require 10 or more standard leukapheresis procedures for the collection of sufficient cells for hematopoietic rescue. STUDY DESIGN AND METHODS: The effectiveness of steady-state large-volume leukapheresis (LVL; 15- 35 L blood processed) was evaluated as a method for collecting MNCs for hematopoietic rescue in seven patients with recurrent Hodgkin's disease. LVL was performed on 2 consecutive days per week to collect 7 × 10(8) MNCs per kg. The circulating MNC counts on the first day of LVL and the total numbers of LVL, of MNCs collected, and of liters of blood processed were determined per patient. After high-dose chemotherapy and MNC transfusion, days to granulocyte and platelet engraftment were recorded. RESULTS: On the first day of LVL, patients had median circulating MNCs of 1536 (range, 504–3950) × 10(6) per L. The median number of LVL procedures per patient was four (range, 1.25-6), and the median L per kg of blood processed was 1.57 (range, 0.38-4.03). Simple regression analysis plotting L per kg against initial MNCs gave a curve with the equation y = e(1.42-(6.31 × 10E-4)x) (correlation coefficient = -0.97, R2 = 0.95, exponential fit). Without posttransfusion growth- factor support, median days to granulocyte engraftment were 19 (range, 12–26) and those to platelet transfusion independence were 34.5 (range, 10–57). CONCLUSION: LVL provides a useful method of collecting MNCs for hematopoietic rescue in patients with Hodgkin's disease. The patient's baseline MNC count provides a useful estimate of the volume required for LVL.     

Midpoint CD34 measurement as a predictor of PBPC product yield in pediatric patients undergoing high-dose chemotherapy

High-dose chemo/radiotherapy of sensitive tumors requires PBPC rescue doses of >3 x 10(6) CD34/kg (range: 3-20 x 10(6) CD34/kg). Because of the diversity of stem cell treatment protocols and clinical presentation of patients at the time of peripheral blood progenitor cell (PBPC) harvest, the use of the mid-point CD34 positive cell measurement was initiated to predict the final CD34-positive cell product yield/stem cell harvest. The measurement of CD34-positive cells at the mid-point of the initial setting of 5 total blood volumes (TBV) allows for the extension, shortening, or no change in the TBV processing to achieve a maximum goal of CD34-positive cells/kg body weight required for stem cell transplantation. The estimation of mid-point CD34-positive cells guided our center to extend 22 procedures, shorten 26 procedures, and leave 20 procedures unchanged. This investigation addresses three aspects of PBPC collection in pediatric patients: (1) the processing of large blood volumes (more than the defined 3 TBV and maximum up to 13 TBV in one session) to achieve good efficiency of the procedure; (2) the use of the mid-point CD34 measurement at 2.5 of 5 TBV initially set to predict the maximum goal of CD34 cells /kg needed on the same day of PBPC collection; and (3) PBPC collection in pediatric patients <10 kg body weight (as low as 5.8 kg body weight).     

A prospective, randomized, sequential, crossover trial of large-volume versus normal-volume leukapheresis procedures: effect on progenitor cells and engraftment

BACKGROUND: The influence of leukapheresis size on the number of harvested peripheral blood progenitor cells is still unclear. A prospective randomized crossover trial was thus performed, to evaluate the effect of large-volume leukapheresis (LVL) versus normal-volume leukapheresis (NVL) on progenitor cells and engraftment in 26 patients with breast cancer and 15 patients with non-Hodgkin's lymphoma who were eligible for peripheral blood progenitor cell transplantation. STUDY DESIGN AND METHODS: Patients were randomly assigned to undergo either LVL on Day 1 and on Day 2 or vice versa. The number of progenitor cells was evaluated in the harvest and before and after leukapheresis in the peripheral blood. RESULTS: The number of harvested CD34+ cells (4.8 x 10(6) vs. 3.4 x 10(6)/kg body weight, p < 0.001) and colony-forming units-granulocyte-macrophage (3.1 x 10(5) vs. 2.4 x 10(5)/kg body weight, p = 0.0026) was significantly higher for LVL procedures than for NVL procedures. The median extraction efficacy, defined as the difference between the yield in the harvest and the decrease in the total number of CD34+ cells in peripheral blood during leukapheresis, was significantly (p < 0.0001) higher for LVL than for NVL (2.6 x 10(8) and 8 x 10(7), respectively). In patients with breast cancer, the median amount of CD34+ cells in the harvest and the median extraction efficacy were higher for LVL than for NVL (p < 0.0001). This was not found for patients with non-Hodgkin's lymphoma. CONCLUSION: LVL results in a higher yield of CD34+ cells and colony-forming units-granulocyte-macrophage than NVL, but only in patients with breast cancer and with high numbers of CD34+ cells in the peripheral blood before leukapheresis.     

Large-volume leukapheresis using femoral venous access for harvesting peripheral blood stem cells with the Fenwal CS 3000 Plus from normal healthy donors: predictors of CD34+ cell yield and collection efficiency

The current paper reports on the predicting factors associated with satisfactory peripheral blood stem cell collection and the efficacy of large-volume leukapheresis (LVL) using femoral vein catheterization to harvest PBSCs with Fenwal CS 3000 Plus from normal healthy donors for allogeneic transplantation. A total of 113 apheresis procedures in 57 patients were performed. The median number of MNCs, CD3+ cells, and CD34+ cells harvested per apheresis was 5.3 x 10(8)/kg (range, 0.3-11.0 x 10(8)/kg), 3.0 x 10(8)/kg (range, 0.2-6.6 x 10(8)/kg), and 7.9 x 10(6)/kg (range, 0.1-188.9 x 10(6)/kg), respectively. The median collection efficiency of MNCs and CD34+ cells was 49.8% and 49.7%, respectively. A highly significant correlation was found between the collected CD34+ cell counts and the pre-apheresis WBC counts in the donors (P = 0.013), and between the collected CD34+ cell counts and the pre-apheresis peripheral blood (PB) CD34+ cell counts (P<0.001). Harvesting at least >4 x 10(6)/kg CD34+ cells from the 1st LVL was achieved in 44 (77.2%) out of 57 donors and in 19 (90.5%) out of 21 donors with a PB-CD34+ cell count of >40/microl. There was no significant difference in the harvested MNC and CD34+ cell counts between the 1st and 2nd apheresis. The catheter-related complications included catheter obstruction (n = 2) and hematoma at the insertion site (n = 3). Accordingly, LVL using femoral venous access for allogeneic PBSC collection from normal healthy donors would appear to be safe and effective.     

Large-volume leukapheresis for peripheral blood stem cell collection in patients with hematologic malignancies

Large-volume leukapheresis (LVL, 15-35 L) was performed in two groups of patients (n = 10) with hematologic malignancies to obtain peripheral blood stem cells for bone marrow rescue following high-dose chemotherapy. The target cell count was 7 x 10(8) mononuclear cells (MNCs = lymphocytes and monocytes) per kg of body weight. Group A patients (n = 4) were studied on Day 1 of LVL, and components were collected from them as four sequential samples. Total MNCs collected averaged 1.29 x 10(10), total colony-forming-units granulocyte-macrophage (CFU-GM) averaged 12.1 x 10(6), and a 1.8-fold mobilization of CFU-GM was observed (p < 0.05, Sample 1 vs. Sample 4). Group B patients (n = 6) were studied throughout the three consecutive planned days of 5-hour LVL. An average of three LVL procedures per patient was performed (range, 1.25-4), and an average of 27 L (range, 24-33) of blood per LVL was processed. The blood:ACD-A ratio was 24:1 with 3000 units of heparin per 500 mL of ACD-A; heparin was also added to the collection bags. The component had an average hematocrit (Hct) of 0.02 and MNC content of 93 percent. The patients' pre-LVL and post-LVL average Hct varied significantly (before Day 1, 0.36 +/- 0.08; after Day 3, 0.28 +/- 0.06; p < 0.05). Platelet counts also decreased, with post-Day 3 counts averaging 19 percent of the average pre-Day 1 counts (p < 0.05). A decrease in the average MNC count after LVL was significant on Day 1 only (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Allogeneic blood progenitor cell collection in normal donors after mobilization with filgrastim: the M.D. Anderson Cancer Center experience

BACKGROUND: Information on the safety and efficacy of allogeneic peripheral blood progenitor cell (PBPC) collection in filgrastim-mobilized normal donors is still limited. STUDY DESIGN AND METHODS: The PBPC donor database from a 42-month period (12/94-5/98) was reviewed for apheresis and clinical data related to PBPC donation. Normal PBPC donors received filgrastim (6 microg/kg subcutaneously every 12 hours) for 3 to 4 days and subsequently underwent daily leukapheresis. The target collection was > or =4 x 10(6)CD34+ cells per kg of recipient's body weight. RESULTS: A total of 350 donors were found to be evaluable. Their median age was 41 years (range, 4-79). Their median preapheresis white cell count was 42.8 x 10(9) per L (range, 18.3-91.6). Of these donors, 17 (5%) had inadequate peripheral venous access. Leukapheresis could not be completed because of apheresis-related adverse events in 2 donors (0.5%). Of the 324 donors evaluable for apheresis yield data, 221 (68%) reached the collection target with one leukapheresis. The median CD34+ cell dose collected (first leukapheresis) was 462 x 10(6) (range, 29-1463).The main adverse events related to filgrastim administration in donors evaluable for toxicity (n = 341) were bone pain (84%), headache (54%), fatigue (31%), and nausea (13%). These events were rated as moderate to severe (grade 2-3) by 171 (50%) of the donors. In 2 donors (0.5%), they prompted the discontinuation of filgrastim administration. CONCLUSION: PBPC apheresis for allogeneic transplantation is safe and well tolerated. It allows the collection of an "acceptable" PBPC dose in most normal donors with one leukapheresis, with minimal need for invasive procedures.     

Volume-dependent collection of peripheral blood progenitor cells during large-volume leukapheresis for patients with solid tumours and haematological malignancies

We investigated the efficacy of peripheral blood progenitor cell (PBPC) collection during large-volume leukapheresis (LVL) in patients with solid tumours and haematological malignancies (n = 18). The time- and volume-dependent harvest of leucocytes (WBC), mononuclear cells (MNC), CD34+ cells and colony-forming cells (CFU-GM) during LVL was analysed in six sequentially filled collection bags processing four times the patient's blood volumes. The amounts of leucocytes (WBC) and the purity of mononuclear cells (MNC%) did not show any significant changes during LVL. The percentage of CD34+ cells remained constant for the first three bags but consecutively decreased from initially 1.71% CD34+ cells in the beginning of LVL to finally 1.34% CD34+ cells (P = 0.02). The mean numbers of colony-forming cells (CFU-GM) decreased from 74 microL-1 to 59 microL-1 during LVL (P = 0.16). Furthermore, the comparison of volume-dependent PBPC collection for patients with high, medium and low total yields of CD34+ cells showed similar kinetics on different levels for the three groups. We concluded that - relative to the initial total amount of PBPC harvested - comparable numbers of progenitor cells can be collected during all stages of LVL with a slight decreasing trend processing four times the patient's blood volumes.     

Leukapheresis after high-dose chemotherapy and autologous peripheral blood progenitor cell transplantation: a novel approach to harvest a second autograft

BACKGROUND: Autologous peripheral blood progenitor cells (PBPCs) are usually collected after the administration of conventional-dose chemotherapy (CDCT) and growth factors. However, there are no data available concerning the collection of PBPCs after high-dose chemotherapy (HDCT) and autologous hematopoietic transplantation in a larger series. STUDY DESIGN AND METHODS: Patients (n = 30) underwent leukapheresis for PBPC harvest after CDCT. After HDCT and autografting, the collection of a second PBPC autograft was attempted. RESULTS: Leukapheresis was performed after CDCT in all cases at a median of 118 CD34+ cells per microL (range, 18-589) and resulted in 6.4 x 10(6) CD34+ cells per kg (range, 1.7-29.0). After HDCT and autografting, 24 patients (80%) underwent secondary leukapheresis, although they had a significantly lower median of peripheral blood (PB) CD34+ cells (30/microL; range, 10-171; p < 0.001). In these patients a median of 3.6 x 10(6) CD34+ cells per kg (range, 1.6-10.1) was collected in the post-transplantation course. In the remaining six patients (20%) with PB CD34+ cells < 10 per microL, no PBPC harvesting was performed. These so-called poor mobilizers had received significantly less CD34+ cells for autologous transplantation than patients with successful post-HDCT mobilization (median, 2.5 x 10(6)/kg [range, 1.7-3.0] vs. 6.5 x 10(6)/kg [range, 3.2-19.6]; p < 0.001). CONCLUSION: Collection of PBPCs is possible in most patients during the recovery phase of hematopoiesis after HDCT plus autografting, and the number of circulating PBPCs may be related to the CD34+ cell dose transfused by the preceding autograft.     

Enhanced HPC recruitment in children using LVL and a new automated apheresis system

BACKGROUND: A new automated apheresis system has recently been reported as useful in improving peripheral blood HPC collection in adults. The aim of this study has been to verify the utility of this system (AutoPBSC, COBE BCT) for standard leukapheresis and for LVL in the pediatric setting. STUDY DESIGN AND METHODS: A prospective study was set up in 29 leukapheresis procedures carried out in 26 children with malignant diseases and body weight under 40 kg who had undergone mobilization with G-CSF or with G-CSF and chemotherapy. Leukapheresis procedures were performed under two protocols, depending on the total blood volume processed: standard leukapheresis (< or=3) and LVL (>3). The need to prime the tubing set with blood was determined, and the inlet flow rate, collection time, recruitment of CD34+ cells, CD34+ cell collection efficiency, component volume, leukapheresis cell composition, and preapheresis and postapheresis peripheral blood counts were measured. Paired t test, Spearman's correlation coefficient, and the Mann-Whitney U test were employed for statistical analysis. RESULTS: Because of the low extracorporeal volume (167 mL) of the tubing set of the automated blood processor, priming was necessary in only 2 of 26 patients, both weighing under 10 kg. LVL showed better CD34+ cell yield (7.5 vs. 2.3 x 10(6)/kg; p = 0.047), higher recruitment (2.1 vs. 0.9; p = 0.002), and greater collection efficiency (50% vs. 33%; p = 0.005) than standard leukapheresis. No significant differences were found between groups in collection time. In LVL procedures, CD34+ cell collection efficiency and recruitment were not significantly influenced by the inlet flow rate. CONCLUSION: The AutoPBSC is a reliable system for peripheral blood HPC collection in children mainly when used in combination with LVL. The major advantage of this software is a reduced need for priming. LVL allows better CD34+ cell collection efficiency, enhanced recruitment, and improved CD34+ cell yield.     

Kinetics of peripheral blood stem cell collection in large-volume leukapheresis for pediatric patients undergoing chemotherapy and adult patients before chemotherapy

The present study investigated the kinetics involved in collection CD34+ cells and colony-forming units-granulocyte-macrophages (CFU-GMs) during large-volume leukapheresis (LVL) in pediatric patients with malignancies and attempted to correlate the number of cells with the processed blood volume. In addition, adult cases were also examined using the same continuous flow blood cell separator to investigate the difference between children and adults. We examined 5 pediatric patients who had undergone chemotherapy before apheresis and 3 adult patients who were scheduled to undergo chemotherapy following apheresis. Collection was performed using a continuous-flow blood cell separator. Patients received granulocyte-colony-stimulating factor (G-CSF) to mobilize peripheral blood stem cells (PBSCs), except in the case of acute myelocytic leukemia. The processed blood volume was set to approximately 300 ml in children and 500 ml/kg of body weight in adults and the leukapheresis component was collected when approximately 50 ml of blood was processed. Six sequential samples were taken from each component in pediatric patients and 10 sequential samples from adults to obtain CD34+ cells and CFU-GMs. Counts of mononuclear cells (MNCs) and CD34+ cells in peripheral blood were measured just before and after each apheresis. Hemoglobin, hematocrit, and platelet counts in peripheral blood were monitored during apheresis. A total of 11 collections were performed for pediatric patients. The mean total CD34+ cells and CFU-GMs in each fractionated yield did not show a remarkable increase with increasing volume of blood processed. In adults, the kinetics of CD34+ cells in each fractionated yield were determined on a continuous basis and CFU-GMs increased during the course of apheresis. In pediatric patients, circulating MNCs and CD34+ cells were stable during apheresis, whereas in adult patients these cells decreased in the peripheral blood after apheresis. In both pediatric and adult patients, the platelet count in the peripheral blood decreased after apheresis. In contrast to adults, in pediatric patients who had been undergone chemotherapy, the collection efficiency did not appear to increase with increased volume of blood processed. Moreover, there was a marked platelet reduction in peripheral blood following apheresis. We conclude that the kinetics of collecting PBSCs by continuous flow blood cell separator is different between pediatric cases and adults cases. The application of LVL may be prudent in some children with malignancies, including those with a low platelet count and low body weight.     

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 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.     

DCEP chemotherapy followed by a single, fixed dose of pegylated filgrastim allows adequate stem cell mobilization in multiple myeloma patients

BACKGROUND: Pegylated filgrastim (PEG-f), a long-lasting granulocyte-colony-stimulating factor, has been used in different hematologic conditions to shorten chemotherapy-induced neutropenia and to mobilize peripheral blood stem cells. Data on mobilization efficacy in patients with multiple myeloma are, however, still limited. STUDY DESIGN AND METHODS: The feasibility and mobilizing capacity of DCEP chemotherapy followed by a single subcutaneous dose of 6 mg of PEG-f in 23 myeloma patients (11 females and 12 males) whose median age was 55 years (range, 31-67 years) were investigated. RESULTS: The median number of CD34+ cells collected was 5.72 x 10(6) per kg body weight with a range between 0 x 10(6) and 29.4 x 10(6) per kg body weight. Twenty patients (87%) yielded more than 2 x 10(6) per kg body weight CD34+ cells. Among the 22 patients who mobilized some CD34+ cells, 27 leukapheresis procedures were carried out (a single leukapheresis procedure in 17 patients and 2 leukapheresis procedures in 5). The median interval between the start of chemotherapy and the first leukapheresis procedure was 12 days (range, 11-16 days). With regard to tolerability, 7 patients complained of mild to moderate back pain, controlled with oral analgesics. No patient was hospitalized, and no fever or infections occurred. CONCLUSION: These results, compared with those previously reported for the DCEP-filgrastim combination, suggest that DCEP chemotherapy followed by PEG-f is a promising combination to mobilize peripheral blood stem cells in myeloma patients.     

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.     

Collection of mobilized blood progenitor cells for hematopoietic rescue by large-volume leukapheresis

BACKGROUND: Mobilized blood progenitor cells rapidly reconstitute hematopoiesis in patients after dose-intensive chemotherapy. However, optimal timing and methods of mobilized blood progenitor cell collection have yet to be fully defined. STUDY DESIGN AND METHODS: The utility of large-volume leukapheresis (LVL; > 15 L blood processed) in collecting target doses of mononuclear cells (7 × 10(8)/kg) for use in autologous hematopoietic rescue was investigated. LVL was begun at a standardized interval (14 days) after a course of limited chemotherapy and subsequent daily recombinant human granulocyte-macrophage-colony- stimulating factor administration to mobilize blood progenitor cells into the circulation. With each LVL procedure, mononuclear cells, colony-forming units-granulocyte-macrophage (CFU-GM), burst-forming units-erythroid, mixed colonies, total clonogenic progenitor cells, and CD34+ cells collected per kg of patient weight were counted. After high- dose chemotherapy and infusion of cryopreserved mobilized blood progenitor cells, the days needed for neutrophils to reach levels of > 0.5 × 10(9) per L and for platelets to reach levels of > 20 × 10(9) per L were recorded. RESULTS: In 14 previously treated cancer patients, an average of 28.9 +/? 4.9 L of blood was processed per LVL (n = 35) to collect medians of 2.5 × 10(8) mononuclear cells per kg (range, 1.0- 7.4), 14 × 10(4) CFU-GM per kg (0-208), 27 × 10(4) clonogenic progenitor cells per kg (0-370), and 2.8 × 10(6) CD34+ cells per kg (0- 112.5). Fifty-seven percent of patients (8/14) required one or two LVL procedures to collect adequate blood progenitor cells (range, 1–4). After dose-intensive chemotherapy, 13 patients received medians of 6.8 × 10(8) mononuclear cells per kg (range, 5.1-9.9), 53 × 10(4) CFU-GM per kg (9-208), and 12 × 10(6) CD34+ cells per kg (3.6-112.5). Rapid hematopoietic reconstitution occurred with 10 days (range, 8–12) and 9 days (6-15), respectively, for neutrophil and platelet recoveries. CONCLUSION: Scheduled LVL, beginning on Day 14 after the administration of granulocyte-macrophage-colony-stimulating factor following chemotherapy, is a convenient and efficient method of collecting blood progenitor cells. The mononuclear cells so obtained effected consistent and rapid hematopoietic reconstitution in a highly reproducible manner in a group of heavily treated patients.     

Application of whole blood and peripheral blood progenitor cells (PBPC) and new strategies for rescue after intensive cyclic chemotherapy in high-risk breast cancer

The efficacy of autologous peripheral stem cells given as mobilized whole blood or leukapheresis product for hematopoietic rescue after intensive chemotherapy was studied in 34 consecutive female patients with high-risk breast cancer. All patients received six cycles of chemotherapy regimen EC (epirubicin 150 mg/m2 and cyclophosphamide 1250 mg/m2) at 14-day intervals. In the first cycle, chemotherapy was given on day 1, and 24 h later mobilization of PBPC was started with G-CSF at a dose of 5 microg/kg/day for 13 days. In all other cycles, G-CSF was given at the same dose from day 7. On days 11, 12, and 13, leukaphereses were performed, and whole blood was collected on day 14 (the peak incidence of colony-forming units-granulocyte-macrophage [CFU-GM] burst-forming units-erythrocyte [BFU-E], and colony-forming unit-granulocyte-erythrocyte-macrophage-megakaryocyte [CFU-GEMM]). The second cycle of chemotherapy was started on day 15, and 24 h later, whole blood (collected in the first cycle) was reinfused, and the same was done in the third cycle. In the fourth to sixth chemotherapy cycles, leukapheresis product was used for hematopoietic rescue. The median increment of absolute values in both whole blood and leukapheresis product was as follows: CD34+ cells over baseline was approximately 17.4-fold, CFU-GM was 85.3-fold, BFU-E was 95.9-fold, and CFU-GEMM was 44.2-fold. In the cycles with whole blood support, the mean values of applied progenitors per cycle were CD34+ cells 1.52 x 10(6)/kg, CFU-GM, 1.18 x 10(5)/kg, BFU-E 2.54 x 10(5)/kg, CFU-GEMM 0.31 x 10(5)/kg. In the courses with PBPC support, the mean values of progenitors were CD34+ 2.04 x 10(6)/kg, CFU-GM 1.59 x 10(5)/kg, BFU-E 2.87 x 10(5)/kg, and CFU-GEMM 0.34 x 10(5)/kg. Leukopenia in patients supported with whole blood versus leukapheresed PBPC was as follows: grade 4, 13/6 (38.2%/17.6%), grade 3, 19/23 (55.9%/70.6%), and grade 2, 1/4 (2.9%/11.8%), respectively. Thrombocytopenia was grade 4, 11/6 (32.4%/17.6%), grade 3, 10/7 (29.4%/20.6%), grade 2, 7/13 (20.6%/38.2%), and grade 1, 6/6 (17.6%/17.6%), respectively. The median follow-up analysis was at 24.6 (7-36) months. High-risk patients previously treated with surgery and adjuvant chemotherapy (n = 5) were not evaluated for response. In 21 patients with locally advanced or inflammatory breast carcinoma the response rate (RR) was 94%, CR was 90%, and PR was 15%. No response to therapy was observed in 1 patient. In 8 patients with metastatic disease, RR was 75%, there was no CR, and PR was 75%. Two patients died during therapy. Relapse-free survival (RFS) in the adjuvant group was 23.7 (range 12-36) months and in the group with locally advanced disease was 18.2 (range 7-27) months. In the group with metastatic disease, time to tumor progression (TTP) was 12.1 (range 1-16) months. Mean duration of hospital stay for whole blood reinfusion in the second and third chemotherapy cycles was 6.7 (range 5-8) days and for PBPC in the fourth to sixth cycles was 6.2 (range 4-8) days, which at p < 0.001 was not statistically significant.     

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.     

A randomized trial of leukapheresis volumes, 7 L versus 10 L: an assessment of efficacy and patient tolerance

High-dose chemotherapy followed by autologous PBSC transplantation (PBSCT) has become an accepted form of therapy for a number of malignant hematologic diseases. The optimal method for the collection of PBSC is yet to be defined. Large-volume leukapheresis may be able to collect adequate numbers of PBSC with the patient undergoing fewer procedures. We routinely process 7 L of blood per leukapheresis. Hence, we elected to assess whether a modest increase in the blood volume processed would, on average, decrease the number of leukaphereses each patient needed to undergo to collect > or =2 x 10(6) CD34+ cells/kg body weight. Sixty patients were randomized to undergo 7 L leukaphereses (n = 31 patients; 87 leukaphereses) or 10 L leukaphereses (n = 29 patients; 81 leukaphereses). The median number of leukaphereses required per patient to collect the target number of CD34+ cells was two (range one to five) for both groups (p = 0.83). The median number of nucleated cells collected per patient was greater for the 10 L group (8.2 x 10(8)/kg versus 5.3 x 10(8)/kg, p = 0.005), as was the median number of mononuclear cells (MNC) (4.7 x 10(8)/kg versus 3.6 x 10(8)/kg, p = 0.0001), whereas there was no statistical difference between the groups for the median number of CD34+ cells collected per patient (3.2 x 10(6)/kg versus 3.7 x 10(6)/kg, p = 0.98). Therefore, over the 18-month period of this trial, the use of a 10 L leukapheresis volume did not decrease the number of leukaphereses performed compared with a 7 L leukapheresis volume.