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.     

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.     

Equivalent mobilization and collection of granulocytes for transfusion after administration of glycosylated G-CSF (3 microg/kg) plus dexamethasone versus glycosylated G-CSF (12 microg/kg) alone

BACKGROUND: The aim of this study was to find a regimen for mobilization and collection of granulocytes that combines low-dose G-CSF administration with satisfactory PMN mobilization and apheresis at a low rate of donor adverse reactions. STUDY DESIGN AND METHODS: In a prospective study, 52 healthy unrelated volunteers received a single subcutaneous injection of glycosylated G-CSF (Lenograstim Chugai-Pharma, Frankfurt, Germany) at medians of 3.1 (range, 2.4-3.6) microg per kg plus dexamethasone (8 mg orally; n = 29) or at 11.8 (7.1-18.5) microg of lenograstim per kg (p < or = 0.0001) without dexamethasone (n = 23) and underwent standard apheresis using the PMN program of a cell separator (Spectra, COBE [now Gambro] BCT). WBC and PMN mobilization results and apheresis yields were compared and the severity and clinical significance of donor adverse reactions was evaluated. RESULTS: For the low-dose G-CSF plus dexamethasone versus the high-dose G-CSF alone group, similar mobilization results were observed for WBCs with 31.3 (19.1-44.9) x 10(9) per L versus 27.5 (19.2-44.0) x 10(9) per L (p = 0.21, NS) and PMNs with 29.0 (17.6-42.2) x 10(9) per L versus 25.2 (16.2-39.0) x 10(9) per L (p = 0.08, NS). The PMN apheresis yields were equal with 70 (39-139) x 10(9) per unit with low-dose G-CSF versus 68 (33-120) x 10(9) per unit in the high-dose G-CSF group (p = 0.83, NS). Regarding donor adverse reactions, 7 out of 29 (24%) and 8 out of 23 donors (35%) reported moderate or severe symptoms. The character of these reactions was different; symptoms of greater clinical significance and a higher need for analgesics were observed in the high-dose G-CSF group. CONCLUSIONS: A Lenograstim dose of 3 microg per kg plus DXM assures effective PMN mobilization and acceptable apheresis components. The combination of glycosylated G-CSF with DXM allows a significant dose reduction in G-CSF for PMN mobilization and collection as compared with higher G-CSF doses alone. In the high-dose G-CSF mobilization group, adverse reactions were more severe and required more analgesics.     

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.     

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.     

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.     

Donor age-related differences in PBPC mobilization with rHuG-CSF

BACKGROUND: Data on the administration of rHuG-CSF to normal donors <18 years old are very limited. STUDY DESIGN AND METHODS: The results of rHuG-CSF administration to 61 donors <18 years old (Group A) were retrospectively evaluated and compared with results from 353 donors > or = 18 years old (Group B) who are included in the Spanish National Donor Registry. The mean age (range) in Group A and B was 14 (1-17) and 38 (18-71) years, respectively (p<0.001). The mean dose of rHuG-CSF was 10 microg per kg per day (range, 9-16) during a mean of 5 days (range, 4-6). Central venous access was placed more frequently in younger donors (25% vs. 6%; p<0.001). RESULTS: The mean number of CD34+ cells collected was 7.6 and 6.9 x 10(6) per kg of donor's body weight in Group A and B, respectively. Fifty-six percent of Group A donors needed only one apheresis to achieve > or = 4 x 10(6) CD34+ cells per kg versus 39 percent of Group B donors (p = 0.01). Side effects were more common in Group B (71% vs. 41%; p<0.001). CONCLUSION: The administration of rHuG-CSF to donors <18 years old leads to CD34+ cell mobilization in a pattern similar to that observed in adults. Greater age was associated with a more frequent requirement for more than one apheresis to achieve a similar number of CD34+ cells.     

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.     

中剂量环磷酰胺或增大环磷酰胺剂量的常规化疗联合G-CSF动员恶性肿瘤患者外周血造血祖细胞

目的　多中心临床研究糖基化的G CSF联合中剂量环磷酰胺 (Cy)或增大针对性联合化疗中Cy剂量动员自体外周血造血祖细胞的效果。方法　北京地区 4所医院 30例患者纳入方案。其中非霍奇金淋巴瘤 (NHL) 2 1例 ,霍奇金病 (HD) 1例 ,乳腺癌 7例及卵巢癌 1例。采用中剂量Cy或以增大Cy剂量为基础的针对性化疗联合G CSF动员自体外周血造血祖细胞 (APBPC)。在化疗后白细胞计数达最低值时开始应用G CSF。当白细胞升至 5 .0× 10 9 L以上时 ,用血细胞分离机采集。结果　Cy平均实际使用剂量为 3.95g(2 .3g m2 ) ;G CSF的剂量分别为 2 5 0 μg d(2 9例 ) ,5 0 0 μg d(1例 ) ,实际剂量3 1～ 6 .4 μg·kg- 1 ·d- 1 。 30例患者平均采集 2 .7次 ,其中 13例采集 2次 ,14例采集 3次 ,3例采集 4次。达到目标采集量单个核细胞≥ 6× 10 8 kg为 2 1例 (70 .0 % ) ,CD34 + 细胞≥ 2× 10 6 kg为 30例 (10 0 % ) ,CFU GM≥ 2× 10 5 kg为 2 4例中 15例 (6 2 .5 % )。 1次采集后 2 7例 (90 .0 % )、2次采集后 2 9例 (96 .7% )患者达到了CD34+ 细胞数目标采集量。结论　G CSF 2 5 0 μg d联合中剂量Cy或以增大Cy剂量为基础的针对性化疗可采集到足够数量的APBPC。     

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.     

Combined administration of G-CSF and dexamethasone for the mobilization of granulocytes in normal donors: optimization of dosing

BACKGROUND: The clinical utility of neutrophil (polymorphonuclear leukocyte, PMN) transfusion therapy has been compromised, in part, by the inability to obtain sufficient quantities of functional neutrophils from donors. Mobilization of PMNs in the peripheral blood of normal volunteers has been shown to be superior when G-CSF is administered in conjunction with dexamethasone to that when either agent is administered alone. The current study was conducted to determine the optimal dosages of G-CSF and dexamethasone to be administered to donors in a granulocyte transfusion program. STUDY DESIGN AND METHODS: Five normal subjects were randomly assigned to each of the following single-dose regimens over five consecutive weeks: 1) subcutaneous (SC) G-CSF at 600 microg and oral (PO) dexamethasone at 8 mg; 2) SC G-CSF at 450 microg and PO dexamethasone at 8 mg; 3) SC G-CSF at 450 microg and PO dexamethasone at 12 mg; 4) SC G-CSF at 450 microg; and 5) PO dexamethasone at 12 mg. Venous blood was collected at 0, 6, 12, and 24 hours after drug administration for determination of absolute neutrophil count (ANC). Side effects of drug administration were recorded by using a standardized symptom questionnaire. RESULTS: Maximal ANC was achieved at 12 hours after administration of drugs under each regimen. All four regimens containing G-CSF caused greater than 10-fold increases in the ANC. When administered in conjunction with dexamethasone, G-CSF resulted in statistically similar PMN mobilization at dosages of 450 microg and 600 microg. The combined single-dose regimen of SC G-CSF at 450 microg and PO dexamethasone at 8 mg increased the mean ANC from a baseline value of 2800 per microL to 37,900 per microL at 12 hours after administration. This regimen was well tolerated by the normal volunteers. CONCLUSION: In a single-dose format designed for clinical granulocyte transfusion programs, optimal PMN mobilization can be achieved in normal donors with a combined regimen of SC G-CSF at 450 microg, and PO dexamethasone at 8 microg.     

Cytokines and vascular cell adhesion molecule-1 in the blood of patients undergoing HPC mobilization

BACKGROUND: The mechanism of HPC mobilization in humans is unclear. In this study, the relationship between PBPC mobilization and blood levels of G-CSF, endogenous cytokines (IL-8, SCF, thrombopoietin [TPO]), and the vascular cell adhesion molecule-1 (VCAM-1) was analyzed in patients with malignancy who were undergoing a PBPC mobilization regimen. STUDY DESIGN AND METHODS: Fifty-four patients with multiple myeloma (MM) and 29 with breast cancer (BC) underwent a mobilization regimen combining conventional chemotherapy and G-CSF up to the last day of PBPC collection. The CD34+ cell count was determined on each day when leukapheresis was scheduled. Venous blood samples (n = 117) were drawn before apheresis for CD34+ cell count (flow cytometry) and cytokine (G-CSF, IL-8, SCF, TPO) and VCAM-1 measurements (ELISA). RESULTS: In multiple regression analysis, SCF was a significant determinant of CD34+ cell levels in BC patients (R = 0.50, p = 0.03) and of VCAM-1 levels in MM patients (R = 0.32, p = 0.02). SCF was negatively correlated with CD34+ cell count in patients with BC. SCF and VCAM-1 blood levels were correlated in MM and BC patients. CONCLUSION: SCF and VCAM-1 could play a role in PBPC mobilization in patients and could be useful measures by which to study patients undergoing a mobilization regimen.     

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.     

Collection of two consecutive neutrophil concentrates for transfusion from donors mobilized with glycosylated granulocyte-CSF plus dexamethasone

BACKGROUND: The objective of this study was to establish a mobilization and apheresis regimen for collection of two consecutive polymorphonuclear neutrophil (PMN) concentrates from the same donor. STUDY DESIGN AND METHODS: In this prospective study, 111 healthy unrelated volunteers underwent either one (Group 1, n = 57) or two consecutive granulocyte apheresis procedure (Group 2, n = 54) using the a cell separator (Spectra). Both Group 1 and 2 donors were initially mobilized with glycosylated G-CSF 6.0 micro g per kg (range, 5.2-7.0 micro g/kg) subcutaneously plus oral dexa-methasone (DXM, 8 mg) and underwent granulocyte apheresis (GA-1) 16 hours (range, 13-18 hr) after initial G-CSF+DXM. Group 2 donors were remobilized with a second DXM dose of 8 mg (n = 13), 4 mg (n = 15), 1.5 mg (n = 13), or none (n = 13), and a second apheresis (GA-2) was run 40 hours (range, 37-42 hr) after G-CSF+DXM administration and 12 hours after remobilization with DXM alone. RESULTS: Based on equivalent median preapheresis WBC and PMN counts of around 35 x 10(9) WBCs per L and 33 x 10(9) PMNs per L after initial mobilization the GA-1 yields were 85 x 10(9) PMNs per U (range, 34-150) in Group 1 and 75 x 10(9) PMNs per U (range, 35-135) in Group 2 (p = 0.14, NS). In Group 2, median preapheresis values of 19.6 x 10(9) WBCs per L (range, 9.5-37.0) and 16.6 x 10(9) PMNs per L (range, 8.8-34.8) were measured after remobilization and GA-2 yields of 49 x 10(9) WBCs per U (range, 26-113) and 42 x 10(9) PMNs per U (range, 21-95) were obtained. Borderline statistical differences in the GA-2 yields were observed from the remobilized donors: 8 mg: 36 x 10(9) PMNs per U (range, 23-60); 4 mg: 47 x 10(9) PMNs per U (range, 21-56) (p 相似文献   

Large-volume leukapheresis in pediatric patients: processing more blood diminishes the apparent magnitude of intra-apheresis recruitment

Background: Recruitment of progenitors during a large-volume collection, as defined by increasing relative and absolute numbers of progenitors (colony-forming units-granulocyte-macrophage [CFU-GM] of CD34+ cells), has been reported previously. Study Design and Methods: To ascertain whether intra-apheresis recruitment occurs in pediatric patients who have undergone mobilization with chemotherapy and granulocyte-colony-stimulating factor (G-CSF), each hour's portion of a 4-hour leukapheresis was collected into separate bags, and assessed by complete blood count, CFU-GM, and CD34+ cell assays. Seven pediatric patients (median age, 7; range, 2–19) were studied in connection with 2 to 4 collections each, for a total of 21 collections (with hourly samples). The collections lasted for 4 hours, at an inlet rate of 1 to 3 mL per kg per minute, for daily processing totals of 5 to 12 blood volumes. (One blood volume [mL] is estimated by the patient's weight in kg × 70 mL/kg.) Smaller (younger) patients had inlet rates exceeding 2 mL per kg per minute, and larger (older) patients had rates of 1 to 1.5 mL per kg per minute. CFU-GM and CD34+ cell counts obtained each hour of the collection and divided by the first hour's value were compared by nonparametric repeated-measures ANOVA. Results: Second-, third- and fourth-hour CD34+ progenitor cell counts were arithmetically higher than first-hour counts, but the trend did not reach significance (p = 0.1561). Second-hour counts were higher than first-hour counts in the overall analysis (mean ± standard error [SE], 1.00 and 1.39 ± 0.1, respectively; p = 0.0525) and in children older than 5 years (1.00 vs. 1.70 ± 0.30, respectively; p = 0.0259), but not in children younger than 5 years (p = 0.8125). CFU-GM counts did not differ among the 4 hours of collection (p = 0.1717) or between the first and second hour (p = 0.9587). Conclusion: In larger (older) patients, from whom fewer blood volumes were collected, there is a trend toward intra-apheresis recruitment, although less than reported previously. In the smaller (younger) patients, from whom more blood volumes were collected, no trend was observed. Lack of (or submaximal) prior mobilization in previously reported studies may have facilitated intracollection recruitment. Alternatively, the larger number of blood volumes collected from the smaller (younger) patients may have masked intra-apheresis recruitment. The study documents the feasibility of large-volume, 4-hour leukapheresis in pediatric patients.     

化疗加G-CSF和GM-CSF联合动员自体外周血干细胞

目的　探讨化疗加粒细胞集落刺激因子 (G CSF)和粒 巨噬细胞集落刺激因子 (GM CSF)联合动员自体外周血干细胞 (APBSC)的效果。方法　卡铂 (CBP) 35 0mg m2 ,第 1天静滴 ;足叶乙甙(Vp16 ) 35 0mg m2 ,第 1～第 3天静滴 ;白细胞降至最低点又回升到 (2 .4～ 6 .4)× 10 9 L时 ,皮下注射G CSF 5 μg·kg- 1 ·d- 1 (早 6∶0 0 ) GM CSF 5 μg·kg- 1 ·d- 1 (晚 6∶0 0 ) 地塞米松 5mg d(采集日 10mg d)直到采集结束前 1天 ;白细胞上升到 (2 9.80± 5 .98)× 10 9 L ,开始用CS30 0 0plus血细胞分离机连续 2d采集APBSC。结果　 2 0例患者连续采集APBSC 2次 ,共采集到MNC(5 .93± 1.6 2 )× 10 8 kg ,CD34 细胞 (2 3.10± 11.5 3)× 10 6 kg ,CFU GM(3.44± 2 .85 )× 10 5 kg。无严重不良反应。 9例 10次自体外周血干细胞移植(APBSCT)造血功能均获满意重建。结论　以化疗联合G CSF和GM CSF能高效、安全地动员APBSC ,1次动员采集 2次可满足 1～ 2次的APBSCT。     

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.     

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.     

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)