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1.
The mobilization and collection of hematopoietic stem and progenitor cells (HSPC) is central to many potentially curative treatments for cancer and some non-malignant conditions. Recombinant human cytokines have been the mainstay of therapeutic HSPC mobilization, particularly G-CSF. Even with currently used mobilization regimens using G-CSF with or without chemotherapy, up to 60% of patients can fail to mobilize enough HSPC for a transplant procedure. Recombinant human stem cell factor (ancestim, rhSCF, Stemgen®) is another such cytokine, which has shown promising synergy when used in combination with G-CSF for HSPC mobilization. It provides a useful second-line option for prior failed-mobilizer patients and those who are anticipated to mobilize poorly due to recognised risk factors. It may also have utility in promoting bone marrow recovery in cases of refractory bone marrow failure such as aplastic anaemia and prolonged non-engraftment after allogeneic HSPC transplantation. We review the literature supporting the use of rhSCF in the context of HSPC mobilization and bone marrow failure. The emergence of other novel agents for HSPC mobilization such as plerixafor (AMD3100, Mozobil?) will further demarcate the role of Ancestim as a second- or third-line mobilization agent for the mobilization-refractory patient.  相似文献   

2.
In contemporary clinical practice, almost all allogeneic transplantations and autologous transplantations now capitalize on peripheral blood stem cells (PBSCs) as opposed to bone marrow (BM) for the source of stem cells. In this context, granulocyte colony-stimulating factor (G-CSF) plays a pivotal role as the most frequently applied frontline agent for stem cell mobilization. For patients classified as high-risk, chemotherapy based mobilization regimens can be preferred as a first choice and it is notable that this also used for remobilization. Mobilization failure occurs at a rate of 10%–40% with traditional strategies and it typically leads to low-efficiency practices, resource wastage, and delayed in treatment intervention. Notably, however, several factors can impact the effectiveness of CD34+ progenitor cell mobilization, including patient age and medical history (prior chemotherapy or radiotherapy, disease and marrow infiltration at the time of mobilization). In recent years, main (yet largely ineffective) approach was to increase G-CSF dose and add SCF, but novel and promising pathways have been opened up by the synergistic impact of a reversible inhibitor of CXCR4, plerixafor, with G-CSF. The literature shows to its favorable results in upfront and failed mobilizers, and it is necessary to use plerixafor (or equivalent agents) to optimize HSC harvest in poor mobilizers. Different CXCR4 inhibitors, growth hormone, VLA4 inhibitors, and parathormone, have been cited as new agents for mobilization failure in recent years. In view of the above considerations, the purpose of this paper is to examine the mobilization of PBSC while focusing specifically on poor mobilizers.  相似文献   

3.
PBSC are the preferred source of stem cells for autologous transplantation. However, regardless of the mobilization procedure used, 10%-20% of patients fail to collect an adequate number to ensure prompt engraftment. There is as yet no standard mobilization procedure for patients who fail a first mobilization attempt. Here, we describe a highly efficient strategy to obtain an adequate number of stem cells for patients who failed a first mobilization attempt. Seventy-four patients with various hematologic malignancies underwent initial mobilization with various regimens including hematopoietic growth factors with or without chemotherapy. In 72% of patients, > or =2 x 10(6) CD34+ stem cells/kg were collected in the initial mobilization attempt, and patients engrafted in a median of 10 days for neutrophils and 12 days for platelets. Eighteen patients failed to mobilize adequate numbers of stem cells, defined as the inability to collect 0.2 x 10(6) CD34+ stem cells/kg/day in the first 2-3 days. These patients had their apheresis halted. Patients were immediately given G-CSF (32 microg/kg/day) for 4 days as a second attempt at mobilization. Eighty-eight percent of these patients achieved the target of > or =2 x 10(6) CD34+ cells/kg, with a median duration of apheresis of 5 days (including the first and second mobilizations). The mean CD34+ cells/kg/day increased after administration of high-dose G-CSF from 0.16 after the first mobilization attempt to 0.61 (p = 0.0002) after the second mobilization. All patients engrafted in a median of 11 and 13 days for neutrophils and platelets, respectively. We conclude that patients whose apheresis yield is <0.4 x 10(6) CD34+ cells/kg after the first two apheresis collections can be successfully mobilized if high-dose G-CSF is administered immediately and continued until achieving > or =2 x 10(6) CD34+ stem cells/kg.  相似文献   

4.
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.  相似文献   

5.
目的:分析普乐沙福联合G-CSF在浆细胞疾病自体造血干细胞中动员的效果及安全性。方法:回顾性分析2018年1月至2019年12月在北京大学人民医院使用普乐沙福联合G-CSF进行自体造血干细胞动员的浆细胞疾病患者的基线临床资料、采集成功率及不良反应。结果:共纳入49例浆细胞疾病患者,多发性骨髓瘤(MM)39例(79.6%...  相似文献   

6.
Background and objectivesConsolidation with autologous stem cell transplantation (ASCT) is recommended for patients with recurrent or refractory lymphoma after salvage chemotherapy. Stem cells which will be used in ASCT are provided by mobilization using granulocyte colony stimulation factor (G-CSF) or chemotherapy plus G-CSF. The aim of this study was to compare the effect of various mobilization regimens on the clinical parameters of lymphoma patients.Materials and methodsMobilization interventions of lymphoma patients were analysed retrospectively. The patients were divided into 3 groups according to the mobilization method implemented to collect stem cells before ASCT, (Group 1: Salvage chemotherapy plus G-CSF, Group 2: Cyclophosphamide plus G-CSF, Group 3: G-CSF alone).ResultsAnalysis of CD34+ cell counts of the 3 groups revealed a significant difference (p < 0.001). Although the number of CD34+ cells collected were different, the neutrophil and platelet engraftment of the 3 groups were similar (p > 0.05). Furthermore, the results were similar in the separate analysis of NHL and HL patients. While the mobilization success rate in group 1 was 97.8 %, it was 90.2 % in group 3. This difference showed a certain trend towards statistical significance (p = 0.074). Patients who received DHAP plus G-CSF had a higher CD34+ count, while neutrophil engraftment was shorter than with ESHAP plus G-CSF (p < 0.05).ConclusionAlthough the success rate of mobilization and number of CD34+ cell collected were higher in the salvage chemotherapy plus G-CSF than G-CSF alone, G-CSF alone group provided similar neutrophil and thrombocyte engraftment in most lymphoma patients.  相似文献   

7.
INTRODUCTION: More than 98% of autologous stem cell transplants are now performed with the support of mobilized blood stem cells, and the proportion of allogeneic blood stem cell transplants has risen to more than 70%. Blood stem cell mobilization strategies are therefore important components of all transplant programs. AREAS COVERED: Stem cell mobilization strategies are evaluated based on current literature, with special focus on the use of plerixafor, a CXCR4 chemokine receptor antagonist. Mobilization methods in autologous settings include the use of G-CSF alone or following chemotherapy (chemomobilization), and the use of G-CSF alone in allogeneic transplants. A combination of G-CSF + plerixafor has been shown to be effective in patients who have failed a previous mobilization. This combination has also been found to be superior to G-CSF alone in Phase III studies in myeloma and non-Hodgkin lymphoma patients as the first-line mobilization. EXPERT OPINION: Addition of plerixafor to chemomobilization or G-CSF mobilization may be more cost-effective than its routine use, and it is worth considering in predicted or proven poor mobilizers. Novel mobilization strategies have allowed more successful stem cell collection in autologous setting, although the effect of plerixafor on graft content and long-term patient outcomes needs further investigation.  相似文献   

8.
Stem cells harvested from peripheral blood are the most commonly used graft source in hematopoietic stem cell transplantation. While G-CSF is the most frequently used agent for stem cell mobilization, the use of G-CSF alone results in suboptimal stem cell yields in a significant proportion of patients undergoing autologous transplantation. Plerixafor (AMD3100, Genzyme Corporation) is a bicyclam molecule that antagonizes the binding of the chemokine stromal cell-derived factor-1 (SDF-1) to its cognate receptor CXCR4. Plerixafor results in the rapid and reversible mobilization of hematopoietic stem cells into the peripheral circulation and is synergistic when combined with G-CSF. In clinical studies of autologous stem cell transplantation, the combination of plerixafor and G-CSF allows the collection of large numbers of stem cells in fewer apheresis sessions and can salvage those who fail G-CSF mobilization alone.  相似文献   

9.
Stem cells harvested from peripheral blood are the most commonly used graft source in hematopoietic stem cell transplantation. While G-CSF is the most frequently used agent for stem cell mobilization, the use of G-CSF alone results in suboptimal stem cell yields in a significant proportion of patients undergoing autologous transplantation. Plerixafor (AMD3100, Genzyme Corporation) is a bicyclam molecule that antagonizes the binding of the chemokine stromal cell-derived factor-1 (SDF-1) to its cognate receptor CXCR4. Plerixafor results in the rapid and reversible mobilization of hematopoietic stem cells into the peripheral circulation and is synergistic when combined with G-CSF. In clinical studies of autologous stem cell transplantation, the combination of plerixafor and G-CSF allows the collection of large numbers of stem cells in fewer apheresis sessions and can salvage those who fail G-CSF mobilization alone.  相似文献   

10.
Autologous stem cell transplantation (ASCT), supported by high-dose chemotherapy, is the prevalent option for multiple myeloma (MM) treatment in candidates suitable for transplantation. Although granulocyte colony-stimulating factor (G-CSF) supported cyclophosphamide (CY) is used as the pre-ASCT mobilization regimen, there is no consensus on the optimal dosage of CY. Thus, in this study, we examined the results of 47 MM patients, who underwent ASCT after mobilization with intermediate (ID) or low-dose (LD) CY treatment supported with G-CSF. As the mobilization regimen, we used ID (2.4 g/m2) of CY in 22 patients, and LD (1 g/m2) of CY in 25 patients. Adequate doses of CD34+ cells were collected in both groups. At the same time, febrile neutropenia was observed to be less common in patients in the LD-CY group. Additionaly 96% of patients in LD-CY group did not need to be hospitalized during the mobilization. In conclusion, we think that mobilization with LD-CY and G-CSF is advantageous since it results in a sufficient amount of stem cells in addition to being advantageous in terms of patient safety and cost.  相似文献   

11.
Introduction: More than 98% of autologous stem cell transplants are now performed with the support of mobilized blood stem cells, and the proportion of allogeneic blood stem cell transplants has risen to more than 70%. Blood stem cell mobilization strategies are therefore important components of all transplant programs.

Areas covered: Stem cell mobilization strategies are evaluated based on current literature, with special focus on the use of plerixafor, a CXCR4 chemokine receptor antagonist. Mobilization methods in autologous settings include the use of G-CSF alone or following chemotherapy (chemomobilization), and the use of G-CSF alone in allogeneic transplants. A combination of G-CSF + plerixafor has been shown to be effective in patients who have failed a previous mobilization. This combination has also been found to be superior to G-CSF alone in Phase III studies in myeloma and non-Hodgkin lymphoma patients as the first-line mobilization.

Expert opinion: Addition of plerixafor to chemomobilization or G-CSF mobilization may be more cost-effective than its routine use, and it is worth considering in predicted or proven poor mobilizers. Novel mobilization strategies have allowed more successful stem cell collection in autologous setting, although the effect of plerixafor on graft content and long-term patient outcomes needs further investigation.  相似文献   

12.
Jantunen E  Lemoli RM 《Transfusion》2012,52(4):906-914
Mobilized peripheral blood (PB) is the preferred source of stem cells (PBSCs) for autologous stem cell transplantation (ASCT). The use of cytokines, alone or in combination with chemotherapy (chemomobilization), is currently the most common strategy applied to collect PBSCs. However, a significant proportion of patients with lymphoid malignancies fail to mobilize enough PBSCs to proceed to ASCT. Plerixafor has been recently introduced for clinical use to enhance PBSC mobilization and has been shown to be more effective than granulocyte-colony-stimulating factor (G-CSF) alone in patients with multiple myeloma or non-Hodgkin's lymphoma. There is limited experience on combining plerixafor with chemotherapy plus G-CSF in patients who mobilize poorly. This review attempts to summarize the published experience on the preemptive use of plerixafor after chemomobilization or G-CSF mobilization to enhance stem cell collection and to prevent mobilization failure. Current evidence suggests that addition of plerixafor is safe and effective in the large majority of the patients with low blood CD34+ cell counts after mobilization and/or poor yield after the first collection(s). Circulating CD34+ cell counts can be increased by severalfold with plerixafor and the majority of the patients considered difficult to mobilize can be successfully collected. Although more studies are needed to evaluate proper patient selection and optimal timing for the addition of plerixafor after chemotherapy, its mechanism of action inducing the rapid release of CD34+ cells from the marrow to the PB makes this molecule suitable for its "preemptive" use in patients who are difficult to mobilize.  相似文献   

13.
IntroductionInduction treatment followed by autologous stem cell transplantation (ASCT) has been accepted as the standard treatment for multiple myeloma (MM) patients. Granulocyte colony stimulating agent (G-CSF), chemotherapy or agents likes plerixafor are being used for the mobilization of stem cells from bone marrow. In this study, we evaluated the impact of the mobilization methods on the outcome of MM patients after ASCT.MethodThe data of 205 MM patients who underwent ASCT at our center between December 2009 and January 2019 were retrospectively analyzed. Patients were divided into 2 groups as good mobilizers (patients who were mobilized with G-CSF alone) and poor mobilizers (patients who were failed to mobilize with G-CSF alone and mobilized with G-CSF + cylophosphomide or G-CSF + plerixafor).ResultsThe median progression free survival (PFS) was 18.27 ± 3.22 months in good mobilizers and 14.22 ± 3.7 months in poor mobilizers. In G-CSF + cyclophosphamide method median PFS was 15.4 ± 4.9 months wheras it was only 4 months in G-CSF + plerixafor method. We did not find a statistically significant difference between good and poor mobilizers regarding median PFS (p: 0.342). The median overall survival (OS) was found 34.48 ± 4.2 months in good mobilizers and 15.13 ± 5.78 months in poor mobilizers. In G-CSF + cyclophosphamide method median OS was 17 ± 14.01 months wheras it was 10.66 ± 7.68 months in G-CSF + plerixafor method. We found a statistically significant difference between good and poor mobilizers regarding median OS (p: 0.007*).ConclusionOur study shows that difficulty in stem cell mobilization is correlated with worse outcome.  相似文献   

14.
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.  相似文献   

15.
Although chemotherapy combined with G-CSF is an effective method for hematopoietic stem cell mobilization, standard chemotherapy protocol leading to best stem cell yield is not defined. In our study, we aimed to assess the impact of chemotherapy choice on mobilization outcome in lymphoma patients. Patients were mobilized with cyclophosphamide (n:15), ASHAP (n:11) or VGEPP (n:12) protocols. Groups were similar according to collected CD34+ cell count, total nucleated cell count and median apheresis days. Five out of fifteen (33%) patients could not be mobilized in Cy group but there was only one failed mobilization attempt in both salvage groups (9% with ASHAP vs 8% with VGEPP). In conclusion, we showed that VGEPP and ASHAP are safe protocols in terms of stem cell mobilization and have similar mobilization capacity as cyclophosphamide alone.  相似文献   

16.
Mobilization of hematopoietic stem cells, which has largely replaced bone marrow harvesting as a source of hematopoietic stem cells, using recombinant agents such as filgrastim or lenograstim has become a standard procedure in both patients and healthy donors prior to peripheral blood stem cell collection for autologous and allogeneic stem cell transplantation. Published literature data suggest that mobilization with recombinant granulocyte-colony stimulating factor (G-CSF) is safe and mobilization outcomes are satisfactory. In recent years, besides G-CSF originators, biosimilar G-CSF agents have been approved by the regulatory agencies for the same indications. Current data showed that by using the biosimilar G-CSF, similar results regarding safety and efficacy of hematopoietic stem cell mobilization may be achieved compared to the originator G-CSF. Although the issues such as the similarity to a licenced biological medicine, differences in manufacturing processes, the potential to cause immunogenicity, extrapolation and interchangeability of these biosimilar products are still being discussed by the scientific area, however, more experience with these agents now exists in approved endications and there seems to be no reason to expect significant differences between biosimilar G-CSF and originator G-CSF regarding their efficacy and safety in both patients and healthy donors. Also, the significant cost savings of biosimilars in real life setting may enhance the use of these agents in the future. Nonetheless, the collection of long-term follow-up data is mandatory for both patients and healthy donors, and multicentre randomized clinical trials that directly compare biosimilar G-CSF with the originator G-CSF are needed in order to allow the transplant community to make informed decisions regarding the choice of G-CSF.  相似文献   

17.
The safety and efficacy of hematopoietic stem cell (HSC) mobilization was investigated in adult splenectomized (SPL) and non-SPL patients with thalassemia major, in two clinical trials, using different mobilization modes: granulocyte-colony-stimulating factor (G-CSF)-alone, G-CSF following pretreatment with hydroxyurea (HU), plerixafor-alone. G-CSF-mobilization was both safe and effective in non-SPL patients. However, in SPL patients the procedure resulted in excessive response to G-CSF, expressed as early hyperleukocytosis necessitating significant dose reduction, and suboptimal CD34(+) cells yields. One-month HU-pretreatment prevented hyperleukocytosis and allowed successful CD34(+) cell collections when an optimal washout period was maintained, but it significantly prolonged the mobilization procedure. Plerixafor resulted in rapid and effective mobilization in both SPL and non-SPL patients and was well-tolerated. For gene therapy of thalassemia, G-CSF or Plerixafor could be used as mobilization agents in non-SPL patients whereas Plerixafor appears to be the mobilization agent of choice in SPL adult thalassemics in terms of safety and efficacy.  相似文献   

18.
The collection efficiency (CE) of the Fenwal CS3000 in collecting peripheral blood stem cells during post-chemotherapy recovery phase ranges from 58% to 73%. Recently filgrastim (recombinant methionyl human granulocyte colony-stimulating factor [G-CSF]) has also been shown to be effective as a mobilization agent although mobilization occurs during elevated and not low normal leukocyte counts. We compared the mononuclear cell (MNC) CE and the myeloid progenitor cell (CFU-GM) CE among 11 patients with G-CSF mobilization (33 procedures) and 19 patients during recovery following myelosuppression chemotherapy (93 procedures). Pre-apheresis leukocyte, neutrophil, MNC, and PB CFU-GM counts were significantly higher in the G-CSF group, while the granulocyte percentage in the apheresis products was similar in both groups. Both MNC CE (81.8 ± 4.5% vs. 64 ± 2.4%) and CFU-GM CE (79.5 ± 10.5% vs. 55.8 ± 3.5%) were higher in the G-CSF group. Only the pre-apheresis MNC count showed an independently significant correlation for both CE (P <.001). The higher CE in the G-CSF group can only be partly explained by a rise in MNC count during apheresis. These data suggest that the blood cell separator works better with leukocytosis, and especially with a higher MNC count. The improvement in CE is another benefit of G-CSF mobilization over chemotherapy mobilization. © 1994 Wiley-Liss, Inc.  相似文献   

19.
Data regarding effects of cholesterol levels on hematopoietic stem cell mobilization are limited. We retrospectively reviewed the relationship between serum total cholesterol levels and peripheral blood CD34 (PBCD34) cell counts in 52 granulocyte colony stimulating factor (G-CSF) induced mobilization cycles with or without chemotherapy. The cholesterol levels between the poor and good mobilization groups (median 172mg/dl vs. 183.5mg/dl, respectively, p=0.18) were not different. No significant correlation was obtained between the cholesterol levels and PBCD34 counts (r=0.02, p=0.85). No significant correlation was obtained between cholesterol levels and PBCD34 counts in patients neither mobilized with G-CSF alone (r=-0.02, p=0.9) nor G-CSF plus chemotherapy (r=0.04, p=0.8). The results of the study indicate that there was no effect of cholesterol on hematopoietic stem cell mobilization. Prospective cohort studies are needed to demonstrate the effect of cholesterol on mobilization and its extent in humans.  相似文献   

20.
本研究比较CEP+G-CSF与CVP+G-CSF动员方案对非霍奇金淋巴瘤(NHL)患者外周血造血干细胞动员采集及造血恢复的效果。回顾性分析我科收治的57例NHL患者。分组采用CEP+G-CSF与CVP+G-CSF动员方案进行外周血干细胞动员采集,并于预处理结束后回输外周血干细胞,分析动员效果、不良反应及自身移植后造血恢复情况。结果表明:动员期间所有患者外周血白细胞(WBC)计数均降至1.0×109/L以下,血小板(Plt)数降至40×109/L以下。57例患者均采集成功,CEP+G-CSF动员方案组采集单个核细胞(MNC)数和CD34+细胞数明显高于CVP+G-CSF动员方案组(p=0.002和p=0.019)。预处理后所有病例均达到骨髓抑制,CEP+G-CSF和CVP+G-CSF动员方案组WBC数恢复到≥1.0×109/L的平均时间分别为11.4和12.3天(p﹥0.05),Plt数恢复到≥50×109/L的平均时间分别为18.6和19.3天(p﹥0.05)。结论:自体外周血干细胞移植治疗NHL疗效显著,CEP或CVP联合G-CSF方案行外周血干细胞动员均安全有效,临床效果满意,CEP+G-CSF方案动员外周血干细胞效果更好。  相似文献   

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