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   

The predictive value of white cell or CD34+ cell count in the peripheral blood for timing apheresis and maximizing yield

BACKGROUND: The collection of peripheral blood stem and progenitor cells (PBPCs) for transplantation can be time-consuming and expensive. Thus, the utility of counting CD34+ cells and white cells (WBCs) in the peripheral blood was evaluated as a predictor of CD34+ cell yield in the apheresis component. STUDY DESIGN AND METHODS: The WBC and CD34+ cell counts in the peripheral blood and the apheresis components from 216 collections were assessed. Sixty-three patients underwent mobilization with chemotherapy plus filgrastim, and 17 patients and 14 allogeneic PBPC donors did so with filgrastim alone. The relationship between the number of WBC and CD34+ cells in the peripheral blood and in the apheresis component was analyzed by using rank correlation and linear regression analysis. RESULTS: The correlation coefficient for CD34+ cells per liter of peripheral blood with CD34+ cell yield (x 10(6)/kg) was 0.87 (n = 216 collections). This correlation existed for many patient and collection variables. However, patients with acute myeloid leukemia had fewer CD34+ cells in the apheresis component at any level of peripheral blood CD34+ cell count. Components collected from patients with CD34+ cell counts below 10 x 10(6) per L in the peripheral blood contained a median of 0.75 x 10(6) CD34+ cells per kg. When the WBC count in the blood was below 5.0 x 10(9) per L, the median number of CD34+ cells in the peripheral blood was 5.6 x 10(6) per L (range, 1.0-15.5 x 10(6)/L). A very poor correlation was found between the WBC count in the blood and the CD34+ cell yield (p = 0.12, n = 158 collections). CONCLUSION: The number of CD34+ cells, but not WBCs, in the peripheral blood can be used as a predictor for timing of apheresis and estimating PBPC yield. This is a robust relationship not affected by a variety of patient and collection factors except the diagnosis of acute myeloid leukemia. Patients who undergo mobilization with chemotherapy and filgrastim also should undergo monitoring of peripheral blood CD34+ cell counts, beginning when the WBC count in the blood exceeds 1.0 to 5.0 x 10(9) per L.     

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.     

Expression of the adhesion molecules CD49d and CD49e on G-CSF-mobilized CD34+ cells of patients with solid tumors or non-Hodgkin's and Hodgkin's lymphoma and of healthy donors is inversely correlated with the amount of mobilized CD34+ cells

The yield of CD34+ PBPC and colony-forming units-granulocyte-macrophage (CFU-GM) in leukapheresis products and the expression of the adhesion molecules CD11a, CD31, CD49d, CD49e, CD54, CD58, CD62L, c-kit (CD117), Thy-1 (CD90), CD33, CD38, and HLA-DR on CD34+ PBPC were analyzed in patients with cancer of the testis (n = 10), breast cancer (n = 10), Hodgkin's disease (n = 20), high-grade (n = 20) and low-grade (n = 20) non-Hodgkin's lymphoma, and healthy donors (n = 20) undergoing G-CSF (filgrastim)-stimulated PBPC mobilization. For each disease entity, G-CSF was administered in two different doses, 10 microg G-CSF/kg body weight (BW)/day s.c. vs. 24 microg G-CSF/kg BW s.c./day in steady-state condition. Data were compared for each dose group separately. Patients with cancer of the testis and breast cancer mobilized significantly more CD34+ cells than patients with high-grade and low-grade non-Hodgkin's lymphoma and Hodgkin's disease (p<0.05). Correspondingly, expression of CD49d on CD34+ PBPC was significantly lower in the same patients with cancer of the testis compared with high-grade and low-grade non-Hodgkin's lymphoma and Hodgkins' disease and in patients with breast cancer compared with high-grade and low-grade non-Hodgkin's lymphoma, Hodgkins's disease, and healthy donors. Similar results were obtained for CD49e. These data suggest that the expression of the adhesion molecules CD49d and CD49e on G-CSF-mobilized CD34+ cells of patients with solid tumors, non-Hodgkin's lymphoma, Hodgkin's disease, and healthy donors is inversely correlated with the amount of mobilized CD34+ cells.     

Factors affecting mobilization of CD34+ cells in normal donors treated with filgrastim

BACKGROUND: Multiple days of apheresis are required for some normal peripheral blood progenitor cell (PBPC) donors, to ensure a sufficient collection of CD34+ cells for allografting. It would be of practical value to be able to identify the patients with poor mobilization on the basis of simple pretreatment clinical or hematologic variables. STUDY DESIGN AND METHODS: Clinical characteristics and laboratory data for 119 normal PBPC donors who underwent apheresis on Days 4 to 6 of treatment with granulocyte-colony-stimulating factor (filgrastim) were analyzed for correlations with CD34+ cell yield from the first day of apheresis. RESULTS: The CD34+ cell yield was significantly lower in donors who were more than 55 years of age, who underwent apheresis on Day 4 of filgrastim therapy, or who were not obese. There were weak direct correlations between CD34+ cell yield and the baseline white cell count, preapheresis white cell count, and preapheresis mononuclear cell count, and there was a weak inverse correlation with age. Twenty- one donors (18%) were considered to have poor mobilization (< 20 × 10(6) CD34+ cells/L blood processed). In the multivariate analysis, the only significant factor was age greater than 55 years, which conferred a 3.8 times greater risk (95% CI, 1.1-13.7) of poor mobilization (p = 0.04). However, poor mobilization occurred in all age groups, so the predictive value of the model was low. CONCLUSION: Donor variables correlated with CD34+ cell yield only weakly, so no particular clinical characteristic can be used to exclude an individual as a PBPC donor if he or she is otherwise suitable for the apheresis procedure.     

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 μg 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] μg/kg/day). Group 2 included 45 patients who received a standard G–CSF dose of 6.0 (5.5-8.1) μg 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 × 10⁶ 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.     

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.     

Peripheral blood progenitor cell collection without close monitoring of peripheral blood CD34+ cells: A feasible strategy for multiple myeloma or pre-treated Non-Hodgkin’s Lymphoma patients mobilized with low-dose cyclophosphamide plus G-CSF

BackgroundDaily monitoring of peripheral blood CD34+ cells may not be necessary for all patients with hematologic malignancies for adequate peripheral blood progenitor cells (PBPC) mobilization and harvesting. We therefore designed a regimen for PBPC mobilization in patients with multiple myeloma or pre-treated Non-Hodgkin’s lymphoma based on a combination of low-dose cyclophosphamide (Cy) plus granulocyte colony-stimulating factor (G-CSF) without daily monitoring of peripheral blood CD34+ cells.Study design and methodsA prospective study was performed on patients with multiple myeloma (n = 22) or pre-treated Non-Hodgkin’s lymphoma (n = 17) whose PBPC were harvested according to the following regimen: 1.5 g/m² Cy at day 1, 12 μg/kg/day G-CSF from day +7 to +11 avoiding daily monitoring of peripheral blood CD34+ cells and two consecutive leukapheresis at days +12 and +13. The optimum threshold of 2 × 10⁶ CD34+ cells per kg was established.ResultsThe proportion of patients with higher CD34+ cell yield after two leukapheresis was similar: multiple myeloma (16/22–72.7%) and Non-Hodgkin’s lymphoma (12/17–70.6%). Exposure to radiotherapy and greater than two prior chemotherapy regimens were significantly associated with lower yield in multiple myeloma (p = 0.002) and Non-Hodgkin’s lymphoma patients (p = 0.002), respectively.ConclusionOur data suggested that adequate yields of CD34+ cells may be achieved in multiple myeloma or pre-treated Non-Hodgkin’s lymphoma mobilized with low-dose Cy plus G-CSF regardless of the daily monitoring of peripheral blood CD34+ cells.     

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.     

Optimization of CD34+ collection for autologous transplantation using the evolution of peripheral blood cell counts after mobilization with chemotherapy and G-CSF.

BACKGROUND: Peripheral blood progenitor cells (PBPC) collection after high dose chemotherapy can be influenced by several factors. We searched for parameters that may predict the best day to start harvesting of PBPC in order to collect most CD34+ cells with the least number of aphereses. METHODS: We studied patients who underwent mobilization chemotherapy for autologous transplantation. The influence of age, sex, diagnosis, number of previous chemotherapy cycles, peripheral blood (PB) counts at day of mobilization (D0), day of neutrophils <1.0 x 10(9) l(-1) and day of nadir and interval between both (delta) on harvesting was investigated. Multivariate linear correlation models were built to predict the best harvesting with principles of parsimony. In patients where sequential CD34+ cell count was performed, the theoretical day of peak was calculated by interpolation in polynomial regression. RESULTS: One hundred and thirty four patients entered the analysis: 36 Hodgkin's lymphoma (HL), 65 B-large cell lymphoma (NHL) and 33 multiple myeloma (MM). Day of harvesting correlated with nr CHT, hemoglobin on D0, day of granulocytes <1.0 x 10(9) l(-1), delta and dosis of mobilization therapy. The day of CD34+ peak could be calculated by the formula = (-0.41) x Hemoglobin D0 + (day peripheral CD34+ cells = 10 x 10(6) microl(-1)) x 0.99 + 7.8. This model could explain 81% of the variance of the peak day and was stable by bootstrap resampling. Day of peripheral CD34+ cells = 10 x 10(6) microl(-1) preceded the calculated peak by 3-9 days. CONCLUSIONS: Although the day of best collection can be predicted using only sequential PB counts after mobilization chemotherapy, a model of prediction using peripheral CD34+ cell count is important especially for optimizing collection in poor mobilizing patients.     

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.     

Peripheral blood progenitor cell collection after epirubicin, paclitaxel, and cisplatin combination chemotherapy using EPO-based cytokine regimens: a randomized comparison of G-CSF and sequential GM-/G-CSF

BACKGROUND: The peripheral blood progenitor cell (PBPC) mobilization capacity of EPO in association with either G-CSF or sequential GM-CSF/G-CSF was compared in a randomized fashion after epirubicin, paclitaxel, and cisplatin (ETP) chemotherapy. STUDY DESIGN AND METHODS: Forty patients with stage IIIB, IIIC, or IV ovarian carcinoma were enrolled in this randomized comparison of mobilizing capacity and myelopoietic effects of G-CSF + EPO and GM-/G-CSF + EPO following the first ETP chemotherapy treatment. After ETP chemotherapy (Day 1), 20 patients received G-CSF 5 microg per kg per day from Day 2 to Day 13 and 20 patients received GM-CSF 5 microg per kg per day from Day 2 to Day 6 followed by G-CSF 5 microg per kg per day from Day 7 to Day 13. EPO (150 IU per kg) was given every other day from Day 2 to Day 13 to all patients in both arms of the study. Apheresis (two blood volumes) was performed during hematologic recovery. RESULTS: The magnitude of CD34+ cell mobilization and the abrogation of patients' myelosuppression were comparable in both study arms; however, GM-/G-CSF + EPO patients had significantly higher CD34+ yields because of a higher CD34+ cell collection efficiency (57.5% for GM-/G-CSF + EPO and 46.3% for G-CSF + EPO patients; p = 0.0009). Identical doses of PBPCs mobilized by GM-/G-CSF + EPO and G-CSF + EPO drove comparable hematopoietic recovery after reinfusion in patients treated with identical high-dose chemotherapy. CONCLUSION: The sequential administration of GM-CSF and G-CSF in combination with EPO is feasible and improves the PBPC collection efficiency after platinum-based intensive polychemotherapy, associating high PBPC mobilization to high collection efficiency during apheresis.     

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.     

A prospective randomized trial of two popular mononuclear cell collection sets for autologous peripheral blood stem cell collection in multiple myeloma

BACKGROUND: The COBE Spectra AutoPBSC collection set (AUTO-kit; CaridianBCT) is a popular dual-stage collection set for peripheral blood progenitor (PBPC) collection. Although the AUTO-kit is purportedly equivalent to the white blood cell (WBC) collection set (WBC-kit) for PBPC collection, improved CD34 yields after switching from the AUTO-kit to the WBC-kit were anecdotally observed, particularly in patients with higher WBC counts. A prospective, randomized trial of the AUTO- and WBC-kits for PBPC collection in multiple myeloma (MM) patients was therefore designed.
STUDY DESIGN AND METHODS: Sixty-eight MM patients were prospectively randomly assigned to either the WBC-kit or the AUTO-kit for PBPC collection. Primary study variables included the number of leukapheresis procedures per transplant, CD34/kg yield per procedure, and cumulative CD34/kg yield per mobilization cycle. Results were compared relative to collection kit and mobilization regimen. Statistics and graphics were performed with commercial software.
RESULTS: CD34/kg yields were higher with the WBC-kit, with 94% of chemotherapy-mobilized MM patients collecting 6 million CD34/kg in a single mobilization (p = 0.06). The WBC-kit also had a faster CD34 collection rate relative to peripheral CD34 counts. The AUTO-kit was significantly sensitive to high WBC counts, with a 50% decrease in CD34 collection efficiency and CD34 collection rate. This effect was specific to MM and not observed in lymphoma patients. Granulocyte–colony-stimulating factor mobilization and the AUTO-kit were associated with an increased incidence and severity of infusion reactions.
CONCLUSIONS: The WBC-kit performed consistently better than the AUTO-kit for PBPC collection in chemotherapy-mobilized MM patients, with fewer procedures per mobilization, superior collection rates, and a decreased incidence of infusion reactions.     

Effect of filgrastim administration for steady-state mobilization of peripheral blood stem cells.

To obtain a better (optimal) schedule of peripheral blood stem cell (PBSC) collection by steady-state granulocyte colony-stimulating factor administrations for autologous or allogeneic transplantations, we compared the effect of doses of filgrastim (8 microg/kg/day versus 16 microg/kg/day) for the steady-state mobilization of PBSCs. The effects of a filgrastim dose of 8 microg/kg/day were not significantly different from those of a dose of 16 microg/kg/day. In the group of patients receiving 8 microg/kg/day, the CD34+ cells over 3 x 10(6)/kg donor body weight were harvested in 3 patients who did not have a long history of receiving combination chemotherapy. The administration of 8 microg/kg filgrastim was adopted also for allogeneic PBSC mobilization for 24 healthy donors. All healthy donors donated an adequate number of PBSCs (CD34+ cells over 4 x 10(6)/kg of recipient body weight) and tolerated this mobilization well with no serious complications. In PBSC mobilization with healthy donors, the maximal yields of CD34+ cells from Day 4 to Day 6 were seen on the fifth day in most cases.     

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.     

MAG方案对恶性血液病患者造血干细胞动员作用的研究

目的　研究米托蒽醌 (MTZ)联合大剂量阿糖胞苷 (Ara C)、重组人粒细胞集落刺激因子(rhG CSF)组成MAG方案对恶性血液病患者外周血干细胞的动员作用。方法　 1995年 12月至2 0 0 3年 4月 ,采用MAG方案对 14例恶性淋巴瘤和 2 9例急性白血病患者外周血干细胞进行动员 ,其用量为MTZ 10mg/m2 ,第 2 ,3天 ;Ara C 2 g/m2 ,每 12h 1次 ,第 1,2天 ;rhG CSF 30 0 μg/d。首先用MA方案联合化疗 ,白细胞 <1.0× 10 9/L时开始用rhG CSF ,白细胞回升时用CS 30 0 0plus或CobeSpectra血细胞分离机采集外周血干细胞。结果　 14例恶性淋巴瘤患者除 1例外周血干细胞采集失败外 ,其余 13例均 1次性采集成功 ,所得单个核细胞 (MNC) (3.91± 2 .70 )× 10 8/kg ,CD34 细胞 (17.79± 12 .90 )× 10 6/kg。采集 2 9例急性白血病患者外周血干细胞平均 2 .13次 ,2 4例采集成功 ,5例采集失败 ,所得MNC (3.6 2± 2 .89)× 10 8/kg ,CD34 细胞 (7.37± 6 .6 0 )× 10 6/kg。rhG CSF平均使用时间为 7d。经MAG方案动员后 ,除 8例患者有胃肠道反应、14例患者骨髓抑制期合并感染外无明显不良反应 ,无动员相关死亡。MAG方案动员后进行微小残留病检测 ,部分病例转为阴性。结论　MAG方案在恶性淋巴瘤和急性白血病患者外周血干细胞动员中安全     

Poor mobilizer and its countermeasures

Mobilization failure is a major concern in patients undergoing hematopoietic cell transplantation, especially in an autologous setting, as almost all donor harvests can be accomplished with granulocyte-colony stimulating factor (G-CSF) alone. Poor mobilizers, defined as those with a peripheral blood CD34⁺ cell count ≤20 cells/μl after mobilization preceding apheresis is a significant risk factor for mobilization failure. We recommend preemptive plerixafor plus G-CSF (filgrastim, 10?μg/kg daily) as a first mobilization strategy, which yields sufficient peripheral blood progenitor cells (PBPCs) in almost all patients and avoids otherwise unnecessary remobilization. Preemptive plerixafor is administered in patients with a day-4 peripheral blood CD34⁺ count <15, depending on the disease and the target PBPC amount. Cyclophosphamide is reserved for patients who fail the first PBPC collection. We recommend second mobilization for patients who could not achieve a sufficient PBPC amount with the first mobilization. In these patients, a second attempt with plerixafor plus G-CSF or mobilization with plerixafor in combination with cyclophosphamide and G-CSF is recommended. Increased dose and/or twice daily administration of G-CSF can be considered.     

Lenograstim versus filgrastim in mobilization before autologous hematopoietic stem cell transplantation in patients with multiple myeloma and lymphoma - Single center experience

ObjectivePeripheral blood stem cell transplantation is frequently used in the treatment of various hematological malignancies after intensive chemotherapy. The primary aim of our study is to compare the amount of collected CD34+ cells and engraftment times in patients mobilized with filgrastim or lenograstim.Material and MethodsDemographic and clinical data of multiple myeloma (MM) and lymphoma patients who underwent autologous transplantation and mobilized with G-CSF (filgrastim or lenograstim) without chemotherapy were collected retrospectively.ResultsOne hundred eleven MM and 58 lymphoma patients were included in the study. When mobilization with filgrastim and lenograstim was compared in MM patients, there was no significant difference in neutrophil and thrombocyte engraftment times of lenograstim and filgrastim groups (p = 0.931 p = 0.135, respectively). Similarly, the median number of CD34+ cells collected in patients receiving filgrastim and lenograstim was very similar (4.2 × 10⁶/kg vs 4.3 × 10⁶/kg, p = 0.977). When compared with patients who received lenalidomide before transplantation and patients who did not receive lenalidomide, the CD34+ counts of the two groups were similar. However, neutrophil and platelet engraftment times in the group not receiving lenalidomide tended to be shorter (p = 0.095 and p = 0.12, respectively). When lymphoma patients mobilized with filgrastim and lenograstim were compared, neutrophil engraftment time (p = 0.498), thrombocyte engraftment time (p = 0.184), collected CD34+ cell counts (p = 0.179) and mobilization success (p = 0.161) of the groups mobilized with filgrastim and lenograstim were similar.ConclusionThe superiority of the two agents to each other could not be demonstrated. Multi-center prospective studies with larger numbers of patients are needed.     

Pegfilgrastim‐ versus filgrastim‐based autologous hematopoietic stem cell mobilization in the setting of preemptive use of plerixafor: efficacy and cost analysis

BACKGROUND: Plerixafor enhances the ability of filgrastim (FIL) to mobilize CD34+ cells but adds cost to the mobilization. We hypothesized that replacing weight‐based FIL with flat‐dose pegfilgrastim (PEG) in a validated cost‐based mobilization algorithm for patient‐adapted use of plerixafor would add convenience without increased cost. STUDY DESIGN AND METHODS: A single‐center retrospective analysis compared two consecutive cohorts undergoing FIL or PEG mobilization before autologous hematopoietic stem cell transplantation for multiple myeloma or lymphoma. FIL dose was 10 µg/kg/day continuing until completion of collection and a 12‐mg flat dose of PEG. Peripheral blood CD34+ cells (PB‐CD34+) enumeration was performed on the fourth day after initiation of growth factor. Subjects surpassing a certain target‐specific threshold of PB‐CD34+ started apheresis immediately while subjects with lower PB‐CD34+ received plerixafor with apheresis starting on the fifth day. RESULTS: Overall 68 of 74 in the FIL group and 52 of 57 patients in the PEG group met the mobilization target. Only one patient in each cohort required remobilization. Median PB‐CD34+ on Day 4 was significantly higher in patients in the PEG group (18.1 × 10⁶ vs. 28.7 × 10⁶ cells/L, p = 0.01). Consequently, patients in the PEG group were less likely to require administration of plerixafor (67.5% vs. 45.6%, p = 0.01). Cohorts had near identical mean number of apheresis sessions and comparable CD34+ yield. The estimated cost associated with growth factor was higher in patients in the PEG group, but it was counterbalanced by lower cost associated with use of plerixafor. CONCLUSION: Single administration of 12 mg of PEG is associated with better CD34+ mobilization than FIL allowing for effective, convenient mobilization with less frequent use of plerixafor.