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1.
PURPOSE: Repeated high-dose chemotherapy (HDCT) followed by peripheral-blood progenitor cell (PBPC) transplantation can induce a complete remission in patients with metastatic breast cancer sensitive to standard chemotherapy (CT), but the majority of patients relapse within 1 to 2 years. The immune system is seriously compromised after HDCT, which precludes the development of effective immunotherapy. We investigated whether autologous lymphocytes, reinfused after HDCT, could induce a rapid recovery of T cells. PATIENTS AND METHODS: Three patients were monitored for immune recovery without reinfusion of lymphocytes. In the next 11 patients, stem cells were harvested after CT + granulocyte colony-stimulating factor (G-CSF) and lymphocytes were harvested after CT + granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-2. These patients received stem cells and G-CSF after the first HDCT; stem cells, G-CSF, and lymphocytes after the second; and stem cells, GM-CSF, and lymphocytes after the third HDCT. RESULTS: Patients not receiving lymphocyte reinfusion had a very slow recovery of lymphocytes. In particular, CD4 counts remained low (< 200/microL for 9 months). Lymphocyte reinfusion had a significant effect on the recovery of lymphocytes, T cells, and CD8+ T cells (normalized on day 25). Recovery of CD4+ T cells was significantly accelerated by lymphocyte reinfusion and GM-CSF, leading to counts of 500/microL at 25 days. CONCLUSION: Lymphocyte reinfusion with G-CSF had a significant effect on the recovery of CD8+ T cells, whereas rapid recovery of CD4+ T cells required lymphocyte reinfusion and GM-CSF, which possibly acts as a survival factor through activation of antigen presenting cells. Whether the rapid recovery of CD4+ and CD8+ T cells prevents or delays relapse of the disease should be further investigated.  相似文献   

2.
Administration of granulocyte colony-stimulating factor to patients undergoing high-dose chemotherapy and autologous peripheral blood stem cell transplantation accelerates neutrophil recovery and decreases hospitalization time. The optimal timing for granulocyte colony-stimulating factor infusion remains unknown. In this retrospective, case-controlled, two-armed study, we reviewed our experience at Hahnemann University Hospital to determine whether initiating granulocyte colony-stimulating factor infusions on posttransplant day 0 versus day 8 affects neutrophil recovery time, posttransplant discharge date, total hospital days after high-dose chemotherapy, and autologous peripheral blood stem cell transplantation. All patients hospitalized between 1994 and 1998 at Hahnemann University Hospital, Bone Marrow Transplantation Unit with breast cancer or non-Hodgkin's lymphoma, who underwent high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation and received granulocyte colony-stimulating factor either on posttransplant day 0 (16 patients) or day 8 (16 patients). The day 0 and day 8 groups had no statistically significant differences in age, sex, weight, height, body surface area, disease characteristics, pretransplant harvesting or conditioning regimens, or transplant CD34+ cell counts. Our main outcome measure was the mean time to reach absolute neutrophil count greater than or equal to 0.5 x 10(9)/l, the number of hospital days after transplant, and the total hospital days. The mean days to neutrophil recovery (10.56 versus 9.68, p = 0.48), posttransplant hospital days (13.62 versus 12.81, p = 0.39), and total hospital days (20.25 versus 20.25, p = 1.00) were not significantly different between day 8 and day 0 groups, respectively. No significant effects on neutrophil recovery time, posttransplant hospital days, or total hospital days were observed with the initial granulocyte colony-stimulating factor infusion on day 0 versus day 8 after transplant. Delayed administration may allow substantial cost savings (US$200 x 8 approximately equal to US $1,600 per patient) without affecting clinical outcome. More studies are needed to determine whether greater delay is feasible.  相似文献   

3.
The advent of granulocyte colony-stimulating factor, in particular filgrastim, in clinical use more than 10 years ago made a significant impact on the management of neutropenia and its complications. More recently, the application of pegylation technology has created a second-generation molecule, pegfilgrastim, with significantly altered pharmacokinetic properties. This has allowed for a once per chemotherapy cycle dosing in contrast to the requirement of daily subcutaneous administration for filgrastim. Several randomized trials in nonmyeloid malignancies have proven that a fixed dose of pegfilgrastim 6 mg is at least equivalent to daily filgrastim therapy. Emerging evidence also suggests that pegfilgrastim may be equally employed in the setting of chemotherapy for acute myeloid leukemia, dose-dense chemotherapy and peripheral stem cell mobilization. If confirmed in subsequent Phase III trials, it is likely that pegfilgrastim will eventually succeed filgrastim as the colony-stimulating factor of choice in clinical practice.  相似文献   

4.
BackgroundFilgrastim decreases the time to neutrophil recovery after autologous peripheral blood stem cell transplantation (PBSCT). We hypothesized that single-dose pegfilgrastim would mimic multiple daily doses of filgrastim, resulting in an equivalent shortening of post-PBSCT neutropenia.Patients and MethodsPatients who were eligible for PBSCT and aged ≥ 18 years were identified before high-dose chemotherapy, after the harvesting and cryopreservation of peripheral blood progenitor cells (ie, > 2.5 × 106 CD34-positive cells/kg). Eligible patients received either standard carmustine/etoposide/cytarabine/melphalan (BEAM) or carmustine/etoposide/cytarabine/cyclophosphamide (BEAC) high-dose chemotherapy. Before high-dose chemotherapy, patients were randomly assigned to receive pegfilgrastim 6 mg on day 1 (arm A) or weight-based, dose-adjusted filgrastim beginning on day 1 (arm B) after transplantation until neutrophil engraftment.ResultsOne-hundred and one patients were enrolled between April 2003 and April 2007. Three patients were not treated. Demographics were well-balanced in terms of stage at diagnosis, Eastern Cooperative Oncology Group performance status, histology, and lines of previous therapy. Results (arm A/arm B) pertained to mean doses received (1.0/12.6), mean absolute neutrophil count recovery days (9.3/9.8), red blood cell transfusions (1.7/1.9), red blood cell transfusion units (3.1/3.8), platelet transfusions (3.1/2.8), positive blood culture rate (18%/29.2%), febrile neutropenia (FN; 18%/16.7%), and duration of FN (days; 7.1/6.9). Transplantation-related mortality and grade 3 or 4 adverse events were comparable between arms.ConclusionPegfilgrastim after PBSCT appears equivalent to multiple daily doses of filgrastim. This approach might be considered in lieu of filgrastim, thus obviating the need for multiple daily injections.  相似文献   

5.
  目的  比较化疗+G-CSF与化疗+G-CSF+GM-CSF方案对淋巴瘤患者外周血造血干细胞动员采集及造血重建的效果差异。  方法  回顾性分析2008年5月至2016年10月天津医科大学肿瘤医院血液科收治的61例行自体外周血造血干细胞移植(au-tologous peripheral blood stem cell transplantation,APBSCT)的淋巴瘤患者,分别采用化疗+G-CSF或化疗+G-CSF+GM-CSF方案动员外周血造血干细胞的临床资料。分析动员采集效果及移植后造血重建、发热、抗生素应用等情况。  结果  动员期间所有患者白细胞计数均降至1.0×109/L以下,血小板计数降至40×109/L以下。化疗+G-CSF组患者采集CD34+细胞数的成功率明显低于化疗+G-CSF+GM-CSF组(52.5% vs. 90.5%,P=0.003)。所有患者移植后均顺利完成造血重建,无移植相关死亡。化疗+G-CSF组和化疗+G-CSF+GM-CSF组中性粒细胞、血小板恢复时间及回输后发热、抗生素使用情况差异均无统计学意义(P>0.05)。  结论  化疗+G-CSF+GM-CSF组动员CD34+细胞产率虽然明显高于化疗+G-CSF组,然而移植成功率、中性粒细胞恢复时间、血小板恢复时间及不良反应均无显著性差异,本研究认为化疗+G-CSF+GM-CSF动员方案并未优于化疗+G-CSF动员方案。   相似文献   

6.
The purpose of this trial was to determine the effects of paclitaxel in patients with newly diagnosed metastatic breast cancer scheduled to receive high-dose chemotherapy with peripheral blood stem cell support. Eighty-four patients received anthracycline-based induction and two doses of paclitaxel at 170 mg/m2 (n = 52) or 250 mg/m2 (n = 32). Eighty-two (98%) received cyclophosphamide and etoposide (n = 50) or paclitaxel and cyclophosphamide (n = 32) with granulocyte colony-stimulating factor for mobilization of peripheral blood stem cells, and 79 (94%) received cyclophosphamide, thiotepa, and carboplatin with peripheral blood stem cell support. One patient (1%) died of infection and 56 (67%) died of progressive disease. For patients with measurable disease, the complete response rate was 21% after induction and 29% after paclitaxel (p = 0.54). Results were compared with those of 125 patients who received the same sequence of therapy without paclitaxel. The complete response rate after high-dose chemotherapy was 54% for patients receiving paclitaxel and 62% for those not receiving paclitaxel (p = 0.60). The probabilities of overall survival and event-free survival at 3 years for patients receiving paclitaxel were 46% and 24%, respectively, compared with 54% and 22%, respectively, for patients not receiving paclitaxel (p = 0.62). Further trials evaluating this dose and schedule of paclitaxel in patients with metastatic breast cancer receiving high-dose chemotherapy are not warranted.  相似文献   

7.
目的 探讨在高剂量治疗联合自体外周血干细胞移植的基础上,加用利妥昔单抗治疗侵袭性B细胞淋巴瘤的可行性和疗效.方法 12个癌症研究中心共入组28例侵袭性B细胞淋巴瘤患者,其中22例为新诊断患者,6例为复发患者.每例患者共接受4次利妥昔单抗静脉输注,即在外周血干细胞动员化疗的前1天、动员化疗的第7天、干细胞回输的前1天和回输后的第8天各给予1次,每次375 mg/m2,共1500 mg/m2结果 高剂量治疗后,所有患者均达到完全缓解.中位随访37个月时,全组患者的4年总生存率和无进展生存率分别为75.0%和70.3%,新诊断患者的4年总生存率和无进展生存率均为72.7%.全组患者对利妥昔单抗治疗的耐受性较好,不良反应多为1、2度.结论 在高剂量治疗联合自体造血干细胞移植的基础上加入利妥昔单抗治疗侵袭性B细胞淋巴瘤是可行的,并且可能使患者的生存获益.  相似文献   

8.
The purpose of this study is to determine outcomes for patients with high-risk nonmetastatic breast cancer undergoing high-dose chemotherapy with peripheral blood stem cell support. Forty-three patients with stage II-III disease, five to nine positive axillary lymph nodes, and a median age of 44 years (range, 27-60 years) were enrolled in a study that included: 1) standard dose doxorubicin, 5-fluorouracil, and methotrexate adjuvant therapy; 2) cyclophosphamide, etoposide, filgrastim, and peripheral blood stem cell harvest; and 3) high-dose cyclophosphamide, thiotepa, and carboplatin (CTCb) followed by peripheral blood stem cell infusion. All 43 patients received doxorubicin, 5-fluorouracil, and methotrexate, 42 (98%) received etoposide, and 41 (95%) received CTCb. Thirty-two patients (74%) are alive, 28 (65%) without relapse at a median of 55 months (range, 41-87 months). Two died (5%) of treatment-related causes, (subclavian catheter complication after etoposide and late radiation pneumonitis), and nine other deaths (21%) were associated with recurrent breast cancer. The probabilities of overall and event-free survival at 4 years were 0.77 and 0.67, respectively, compared with 0.82 and 0.69, respectively, for 72 similar patients with 10 or more positive axillary nodes receiving the same sequence of therapy. Thus, patients with five to nine positive axillary lymph nodes have a similar risk of failure after high-dose chemotherapy and peripheral blood stem cell support as patients with 10 or more positive axillary lymph nodes.  相似文献   

9.
BACKGROUND: Peripheral blood progenitor cell transplantation is rapidlyreplacing autologous bone marrow transplantation as hematologicalsupport after high-dose chemotherapy for lymphoma or solid tumors.Controversy exists concerning the number of progenitor cellsrequired for rapid and sustained bone marrow recovery, and asto which of the widely available methods for estimating thisnumber should be employed. METHODS: Forty consecutive patients with solid tumors or lymphomas receivedhigh-dose chemotherapy followed by autologous peripheral stemcell reinfusion. All stem cell harvests had been performed aftermobilization with standard-dose chemotherapy followed by 300µg G-CSF daily. Hematopoietic reconstitution was studiedin relation to pertinent patient characteristics, to the sizeof the graft (in terms of the total number of mononuclear cells(MNC), the number of granulocyte/macrophage colony-forming units(CFU-GM) and the number of CD34+ cells, and to the use of G-CSFafter stem cell reinfusion. RESULTS: Both the numbers of CFU-GM and CD34+ cells reinfused, but notthose of the MNC, correlated with granu-locyte and plateletrecovery. Patients who received at least 5 x 106 CD34+ cells/kgbody weight achieved platelet transfusion independence on day12 after reinfusion (range: day 7–37), significantly earlierthan patients who had received less (p  相似文献   

10.
Macrophage inflammatory protein 1alpha (MIP-1alpha) inhibits haemopoietic stem cell proliferation. This property has been exploited in a murine chemotherapy model and has been shown to ameliorate cytotoxic-induced myelosuppression after S-phase-specific cytotoxic therapy. We have now shown that BB-10010, a stable mutant of MIP-1alpha, (a) is more effective when administered as a continuous infusion than when bolus injected and (b), when administered via a 7-day infusion during and after cyclophosphamide treatment, results in an earlier recovery of leucocyte numbers. This effect was accompanied by progenitor cell mobilization into the peripheral blood and included primitive cells with marrow-repopulating ability (MRA). Maximal mobilization and recovery of leucocytes occurred when MIP-1alpha was combined with granulocyte colony-stimulating factor (G-CSF) therapy. The findings suggest that MIP1-alpha used alone or in combination with G-CSF may allow delivery of a greater chemotherapy dose intensity as a consequence of both accelerated leucocyte recovery and maintenance of high-quality mobilized progenitor cells for harvesting and peripheral blood stem cell transplantation.  相似文献   

11.
The EAP combination of etoposide (ETP), doxorubicin (ADM) and cisplatin (CDDP) has been reported to be highly active for advanced gastric cancer. However, it is associated with severe myelotoxicity, and its use has declined. We examined whether peripheral blood stem cells (PBSCs) could be mobilized during hematopoietic recovery after EAP, and assessed the possibility of using multimodal cell therapy with PBSCs for the treatment of advanced gastric cancer. Five men with advanced gastric adenocarcinoma were enrolled. All patients were chemotherapy-na?ve. EAP (ETP, 360 mg/m2; ADM, 40 mg/m2; CDDP, 80 mg/m2) was given to each patient, and myelotoxicity was carefully monitored. Granulocyte colony-stimulating factor was administered after the neutrophil nadir, and PBSCs were collected by leukapheresis during hematopoietic recovery. The median nadir of the neutrophil count after EAP was 225/ml, occurring between day 17 and 20. Sufficient numbers of PBSCs [CD34(+) cells, CFU-GM] could be mobilized in 4/5 patients. A 45-year-old patient with extended lymph node metastasis received high-dose EAP with peripheral blood stem cell transplantation (PBSCT), followed by cancer vaccine therapy with dendritic cells (DCs), induced from cryopreserved PBSCs. Both high-dose EAP with PBSCT and DC-based immunotherapy was safely performed for the first time against gastric cancer. Although associated with severe myelotoxicity, EAP can mobilize sufficient numbers of PBSCs during hematopoietic recovery. Multimodal cell therapy combining high-dose chemotherapy with PBSCT and DC-based immunotherapy is feasible and can be a reasonable approach in advanced gastric cancer.  相似文献   

12.
13.
Mobilization techniques for peripheral blood stem cell (PBSC) collection include the administration of chemotherapy followed by hematopoietic growth factors or growth factors alone. Two forms of recombinant human granulocyte colony-stimulating factor (rhG-CSF) are available for PBSC mobilization: lenograstim and filgrastim which are the glycosylated and non-glycosylated forms respectively. In order to determine the influence of the two forms of G-CSF following chemotherapy on PBSC collection, we conducted a retrospective study in 126 patients with various hematological malignancies: 65 and 61 for the lenograstim and filgrastim groups respectively. No significant differences between the two groups were observed in terms of sex, age and diagnosis. Prior therapies and PBSC mobilization regimen were also equivalent. No significant difference was observed between the groups for the median CD34+ cells harvested. The number of leukapheresis necessary to obtain a minimal number of 3 x 10(6) CD34+ cells/kg was equivalent for the two groups. The proportion of patients affected by a failure in PBSC collection was similar in the two groups. Our data suggest that lenograstim and filgrastim are equivalent for PBSC mobilization after chemotherapy.  相似文献   

14.
Hematopoietic growth factors are usually administered in autologous and allogeneic stem cell transplantation. RhuG-CSF and rhuEPO are the most frequently used, either for mobilization of peripheral stem cells or after transplantation for the improvement of hematologic recovery. G-CSF (filgrastim or lenograstim) can be administered alone or in combination with stem cell factor to enhance stem cells mobilization. IL-3 and sargramostim are not used anymore. The protocol of administration of rhuG-CSF is well established. Furthermore, stem cell transplantation with peripheral cells is less expensive than with bone marrow. RhuEPO (erythropoietin) is not effective in mobilization. After transplantation, filgrastim or lenograstim can shorten the neutropenic period and decrease infectious complications. The potential effect of these growth factors on the incidence and the severity of GvHD is still unknown and under debate. The use of rhuEPO after transplantation might be of interest to reduce the need of red blood cell transfusion. Some studies suggest that the administration of rhuEPO should start before delivering the conditioning regimen. The new long acting growth factors such as pegfilgrastim are still under evaluation and their use in mobilization seems promising.  相似文献   

15.
We have shown that large numbers of haemopoietic progenitor cells are mobilised into the blood after filgrastim [granulocyte colony-stimulating factor (G-CSF)] alone and filgrastim following cyclophosphamide chemotherapy in previously untreated patients with ovarian cancer. These cells may be used to provide safe and effective haemopoietic rescue following dose-intensive chemotherapy. Using filgrastim alone (10 micrograms kg-1), the apheresis harvest contained a median CFU-GM count of 45 x 10(4) kg-1 and 2 x 10(6) kg-1 CD34+ cells. Treatment with filgrastim (5 micrograms kg-1) following cyclophosphamide (3 g m-2) resulted in a harvest containing 66 x 10(4) kg-1 CFU-GM and 2.4 x 10(6) kg-1 CD34+ cells. There was no statistically significant difference between these two mobilising regimens. We have also demonstrated that dose-intensive carboplatin and cyclophosphamide chemotherapy can be delivered safely to patients with ovarian cancer when supported by peripheral blood progenitor cells and filgrastim. Carboplatin (AUC 7.5) and cyclophosphamide (900 mg m-2) given at 3 weekly intervals with progenitor cell and growth factor support was well tolerated in terms of haematological and systemic side-effects. Double the dose intensity of chemotherapy was delivered compared with our standard dose regimen when the treatment was given at 3 weekly intervals. Median dose intensity could be further escalated to 2.33 compared with our standard regimen by decreasing the interval between treatment cycles to 2 weeks. However, at this dose intensity less than a third of patients received their planned treatment on time. All the delays were due to thrombocytopenia.  相似文献   

16.
Seventy-one patients with poor-prognosis breast cancer were enrolled after informed consent in a multicentre randomized study to evaluate the use of selected peripheral blood CD34+ cells to support haematopoietic recovery following high-dose chemotherapy. Patients who responded to conventional chemotherapy were mobilized with chemotherapy (mainly high-dose cyclophosphamide) and/or recombinant human granulocyte colony-stimulating factor (rhG-CSF). Patients who reached the threshold of 20 CD34+ cells per microl of peripheral blood underwent apheresis and were randomized at that time to receive either unmanipulated mobilized blood cells or selected CD34+ cells. For patients in the study arm, CD34+ cells were selected from aphereses using the Isolex300 device. Fifteen patients failed to mobilize peripheral blood progenitors and nine other patients were excluded for various reasons. Forty-seven eligible patients were randomized into two comparable groups. CD34+ cells were selected from aphereses in the study group. Haematopoietic recovery occurred at similar times in both groups. No side-effect related to the infusion of selected cells was observed. The frequency of epithelial tumour cells in aphereses was low (8 out of 42 evaluated patients), as determined by immunocytochemistry. We conclude that selected CD34+ cells safely support haematopoietic recovery following high-dose chemotherapy in patients with poor-prognosis breast cancer.  相似文献   

17.
Myeloid colony-stimulating factors (granulocyte colony-stimulating factor [G-CSF] and granulocyte-macrophage colony-stimulating factor) are commonly used in clinical practice for the prevention of anticancer chemotherapy-induced neutropenia and its potentially life-threatening complications. Pegfilgrastim is a novel recombinant human G-CSF pharmaceutically developed by covalent binding of a polyethylene glycol molecule to the N-terminal sequence of filgrastim. Due to its unique neutrophil-mediated clearance, pegfilgrastim can be administered once per chemotherapy cycle. Clinical trials have demonstrated that a single, fixed, subcutaneous dose of pegfilgrastim is comparable in safety and efficacy to daily injections of filgrastim for decreasing the incidence of infection following myelosuppressive chemotherapy in patients with cancer. Recent trials have been conducted to evaluate the use of pegfilgrastim in different clinical settings, including support of dose-dense regimens, mobilization and transplantation of hematopoietic stem cells.  相似文献   

18.
We studied the usefulness of rhG-CSF (filgrastim) administration in patients who received autologous peripheral blood stem cell transplantation (PBSCT) combined with super-high dose chemotherapy. Twenty patients received 0-8.3 micrograms/kg/day filgrastim after PBSCT. There was a significant relationship between G-CSF dose and the neutrophil recovery rate, and the highest levels of serum G-CSF tended to correlate with neutrophil recovery rate. The highest G-CSF level after 75 micrograms injection in normal volunteers is reported to be 1,500 pg/ml. On the other hand, as one patient in our series exhibited extremely high endogenous G-CSF of 11,500 pg/ml, measurements of G-CSF might reduce the over-administration of rhG-CSF.  相似文献   

19.
We studied the effect of granulocyte colony-stimulating factoron the magnitude of peripheral blood stem cell mobilizationin patients with malignancy. The leukapheresis products mobilizedwith granulocyte colony-stimulating factor alone at a steadystate (a period of full hematopoietic recovery) (group 1) werecompared with those obtained after cytotoxic chemotherapy usinggranulocyte colony-stimulating factor (group 2). In group 1,six patients underwent six courses of stem cell collection witha median of 20 l leukapheresis. In group 2, 10 patients underwent12 courses of stem cell collection with a median of 10 l leukapheresis.Median yields of group 1 vs. group 2 were mononuclear cells(x109), 21.9 vs. 11.6; CD34+ cells (x106/l), 14.5 vs. 17.1;colony-forming unit for granulocyte-macrophage (/ml), 223 vs.1193; burst-forming unit for erythroid (/ml), 29 vs. 71; colony-formingunit for erythroid (/ml), 42 vs. 29; colony-forming unit formegakaryocyte (/ml), 26 vs. 59. While there were no statisticallysignificant differences in the number of CD34+ cells betweenthe two groups, granulocyte-macrophage-committed progenitorcells were more enriched in the apheresis products of group2. The correlation between CD34+ cells and colony-forming unitfor granulocyte-macrophage was poor. Our results demonstratethat granulocyte colony-stimulating factor can mobilize a sufficientnumber of progenitor cells into the peripheral blood for stemcell transplantation with or without prior chemotherapy.  相似文献   

20.
Recombinant granulocyte colony-stimulating factor (G-CSF) has been shown to decrease the duration of severe neutropenia, the incidence of febrile neutropenic episodes, the overall duration of intravenous antibiotic therapy, and the length of hospitalization in patients receiving myelosuppressive chemotherapy. G-CSF has also been shown to accelerate myeloid recovery after autologous and allogeneic bone marrow transplantation, and to mobilize stem cells in peripheral blood for hematopoietic rescue. However, the optimal dose, schedule, and method of administration of G-CSF in these settings remain to be standardized. This review focuses on the role of G-CSF in bone marrow and peripheral blood stem cell transplantation, and in hematopoietic stem cell mobilization.  相似文献   

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