普乐沙福用于外周血干细胞动员的研究进展

大剂量化疗联合自体外周血干细胞(peripheral blood stem cell,PBSC)移植是淋巴瘤和多发性骨髓瘤(multiple myeloma,MM)的有效治疗手段.PBSC的常规动员方案包括粒细胞集落刺激因子(granulocyte colony-stimulating factor,G-CSF)单用或...     

Engraftment and outcomes following autologous stem cell transplantation in Hodgkin lymphoma patients mobilized with plerixafor

Plerixafor has been used to improve peripheral blood stem cell (PBSC) mobilization in multiple myeloma, non‐Hodgkin lymphoma, and very recently in Hodgkin lymphoma (HL) patients. Because prior studies have suggested that mobilization with plerixafor affects the composition of mobilized cells, there are concerns that this may in turn adversely impact the immune reconstitution and longer term outcomes of transplanted patients. However, data on the engraftment characteristics and long‐term post‐transplant outcomes in patients transplanted with plerixafor‐mobilized PBSCs are lacking. This retrospective study examined the post‐transplant outcomes of 105 consecutive adult HL patients, and compared the post‐transplant outcomes of 21 patients who received plerixafor in addition to G‐CSF ± chemotherapy because of poor mobilization with those of 84 patients who mobilized well without plerixafor. Despite collecting significantly lower CD34+ cell doses (median of 3.41 vs. 6.05 × 10⁶/kg, p < 0.0001) than control patients and requiring more collection days, plerixafor‐mobilized patients showed comparable early engraftment characteristics, except for slightly delayed neutrophil engraftment (median: 11 vs.10 days, p = 0.002) and lower median neutrophil counts (2.1 vs. 2.6 × 10⁹/L, p = 0.04) at one month after transplant. No significant differences were observed in longer term post‐transplant outcomes, including cell counts at 3, 6, and 12 months, RBC and platelet transfusion support during the first 120 days, relapse incidence, overall and progression‐free survival rates up to two years post transplant. The use of plerixafor not only enabled poorly mobilizing HL patients to collect enough PBSCs to proceed to ASCT, but also to have similar post‐transplant outcomes compared to patients who mobilized well with conventional regimens. Copyright © 2016 John Wiley & Sons, Ltd.     

61例淋巴瘤患者自体外周血造血干细胞动员方案临床分析

  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。      

High dose therapy and autologous stem cell transplantation for human immunodeficiency virus-associated non-Hodgkin lymphoma in the era of highly active antiretroviral therapy

BACKGROUND: The advent of highly active antiretroviral therapy (HAART) has allowed the exploration of more dose-intensive therapy such as autologous stem cell transplantation (ASCT) in selected patients with human immunodeficiency virus (HIV)-associated non-Hodgkin lymphoma (NHL). METHODS: The authors report on the use of myeloablative chemotherapy with ASCT in two HIV positive patients with NHL. The first patient underwent ASCT at the time of first disease remission for poor risk, diffuse, large cell NHL and the second patient had multiply recurrent, chemosensitive Burkitt lymphoma. ASCT was performed in both patients using a transplant conditioning regimen of high dose cyclophosphamide, carmustine, and etoposide (CBV). RESULTS: The target dose of >/= 5 x 10(6)/kg CD34 positive peripheral blood stem cells (PBSC) utilized for ASCT was collected using granulocyte-colony stimulating factor (G-CSF) after chemotherapy for mobilization while both patients were receiving concomitant HAART for HIV infection. HAART was continued during CBV conditioning. Prompt hematopoietic recovery was observed after ASCT. Both patients remained in clinical disease remission from their lymphoma at 28 months and 20 months after transplant, respectively. CONCLUSIONS: ASCT is feasible in patients with HIV-associated NHL. Adequate numbers of CD34 positive PBSC can be procured from patients receiving HAART and chemotherapy for NHL. Selected patients with HIV-related lymphoma can tolerate the high dose CBV myeloablative chemotherapy regimen without increased acute regimen-related toxicity. Reinfusion of G-CSF-mobilized PBSC can lead to rapid recovery of hematologic function and sustained engraftment after ASCT. Given the poor prognosis of patients with HIV-associated NHL treated with conventional chemotherapy, further investigation of this approach should be considered.     

Poor mobilization of peripheral blood stem cells is a risk factor for worse outcome in lymphoma patients undergoing autologous stem cell transplantation

The effect of poor blood stem cells mobilization on the outcome of autologous stem cell transplantation (ASCT) has not been well studied. Our aim is to evaluate poor mobilization as a prognostic factor in lymphoma patients undergoing ASCT. We analyzed 90 consecutive patients with Hodgkin's (HD) and non-Hodgkin's lymphoma (NHL) who underwent ASCT. Poor mobilization was defined as the inability to obtain > or = 1 x 10(6) CD34+ cells/kg ideal body weight with two large volume aphereses. Patients were divided into 2 groups: group 1 = poor mobilizers, and group 2 = good mobilizers. The poor mobilizers received lower median transplant CD34+ cell dose (2 x 10(6) vs. 4.5 x 10(6)/kg for good mobilizers, P = 0.001), were more heavily pretreated (P = 0.01), and required higher number of aphereses for PBSC collection (P = 0.0006). The median progression-free survival (PFS) in groups 1 and 2 was 10 and 41 months (P = 0.04), while the median overall survival (OS) was 38 months and not reached (P = 0.02), respectively. Univariate analysis showed that > or = 3 pre-transplant treatments, CD34+ cell dose < or = 2 x 10(6), elevated LDH before transplant, and poor mobilization were significant prognostic factors for poor PFS, while only the first three were significant for worse OS. Multivariate analysis using these same four factors revealed that number of pre-transplant treatments (HR = 6.03, P = 0.001), CD34+ cell dose (HR = 0.1, P = 0.0007) were the only independent predictive factors for worse overall outcome. In conclusion, our data show that poor mobilization could indicate poor outcome in lymphoma patients undergoing ASCT, however, it is more likely to be a reflection of the heavy pre-transplant therapy and lower CD34+ cell dose re-infused in this group of patients.     

The Hyper-CVAD chemotherapy regimen has an adverse long-term impact on the ability to mobilize peripheral blood stem cells, which can be readily circumvented by using the early cycles for mobilization

The Hyper-CVAD chemotherapy regimen is being increasingly applied to a number of haematological malignancies. We assessed the impact of Hyper-CVAD on peripheral blood stem cell (PBSC) yields and examined the optimal timing of PBSC collection when using this regimen. Seventy-four consecutive patients were identified in whom an attempt was made to collect PBSC, usually on recovery from cycle A or B. Where PBSC collection was attempted after cycle 3B, only 18% (3/17) of patients successfully mobilized. Fifty-seven patients were mobilized on recovery from cycle 1B (n = 13), 2A (n = 22), 2B (n = 14) or 3A (n = 8). Compared with cycle 2A, 1B was not superior in achieving the minimum of > or =2 x 10(6)/kg CD34+ cells (100% vs. 77%, p = 0.13), but was superior in terms of total CD34+ yield (21.4 vs. 3.2 x 10(6)/kg, p < 0.001), achieving the target CD34+ cell count of > or =5 x 10(6)/kg (92% vs 36%, p = 0.002), and obtaining both a minimum (92% vs. 18%, p < 0.001) and target (77% vs. 0%, p < 0.001) graft with a single apheresis. There were no significant differences in PBSC yields following cycles 2A, 2B and 3A. Hyper-CVAD has substantial stem cell toxicity which can be readily circumvented by using the early chemotherapy cycles for mobilization.     

Efficacy of first-line bleomycin, etoposide, and cisplatin chemotherapy for peripheral blood stem cell mobilization in patients with germ cell cancer

Background We assessed the efficacy of first-line bleomycin, etoposide, and cisplatin (BEP) chemotherapy for the mobilization of peripheral blood stem cells (PBSC) in patients with testicular cancer, and analyzed the predictive factors indicating the optimal time of PBSC harvest. Patients and Methods A total of 29 aphereses, performed during first-line BEP chemotherapy between 1994 and 1996 for 10 patients with metastatic germ cell cancer were analyzed. The predictive value for the optimal time of PBSC harvest was determined by analysis of the correlation between the rate of each cellular component in peripheral blood, and the number of CD34-positive cells harvested. Results The median number of CD34-positive cells obtained at a single apheresis was 11.2×10⁶/kg (range, 0.14 to 47.9×10⁶/kg), and the median cumulative number of CD34-positive cells collected during first-line BEP chemotherapy per patient was 31.9×10⁶/kg (range, 9.7 to 75.5×10⁶/kg). The percentage of immature leukocytes (myelocytes plus metamyelocytes) was significantly correlated with the number of harvested CD34-positive cells. Conclusion Adequate amounts of CD34-positive cells can be harvested during first-line BEP chemotherapy for patients with germ cell cancer. The monitoring of the percentage of immature leukocytes might be useful in ascertaining the optimal time of apheresis.     

High-dose rituximab does not negatively affect peripheral blood stem cell mobilization kinetics in patients with intermediate-grade non-Hodgkin's lymphoma

Rituximab, an anti-CD20 human-mouse chimeric monoclonal antibody has been shown to improve response rates when it is combined with standard salvage chemotherapy in patients with relapsed or refractory intermediate-grade B-cell non-Hodgkin's lymphoma. A vast majority of these patients subsequently undergo high-dose therapy followed by stem cell transplantation. However, the impact of rituximab on stem cell mobilization kinetics is not well characterized. The purpose of this study was to study the effect of high-dose rituximab given with chemotherapy on stem cell mobilization in patients with intermediate-grade B-cell non-Hodgkin's lymphoma. Thirty-six patients received ifosfamide, etoposide, and rituximab followed by filgrastim for stem cell mobilization. The chemotherapy regimen was well tolerated. Thirty-four of 36 patients (94%) were able to mobilize at least 2 × 10⁶ CD34+ cells/kg body weight after a median of 2 apheresis procedures. The median CD34+ cell dose collected per kilogram of recipient body weight was 6.5 × 10⁶ (range, 4.65-31.15). All patients who subsequently underwent high-dose chemotherapy and stem cell transplantation experienced sustained engraftment. In conclusion, high-dose rituximab given during stem cell mobilization does not negatively affect stem cell mobilization kinetics.     

Endothelial cells (EC) and endothelial precursor cells (EPC) kinetics in hematological patients undergoing chemotherapy or autologous stem cell transplantation (ASCT)

Our objective was to study the kinetics of circulating endothelial cells (EC) and endothelial precursor cells (EPC) in hematological patients during chemotherapy and autologous stem cell transplantion (ASCT). Eighteen newly diagnosed patients and 17 patients undergoing ASCT were studied and compared to healthy controls. ECs were evaluated as CD146+CD31+Lin- cells, while EPCs were evaluated as CD34+CD133+Lin-, or CD34+VEGFR2+Lin- cells, or CFU-En colony forming units. Numbers of these cells were evaluated before and after treatment, and, in patients treated with ASCT, during mobilization of hematopoietic progenitors. Both newly diagnosed patients and patients before ASCT had significantly higher number of CD146+CD31+Lin- cells and significantly lower number of CFU-En colonies than healthy controls. These parameters did not return to normal for at least 3 months after chemotherapy or ASCT. Numbers of CFU-En did not correlate either with numbers of CD34+CD133+Lin- cells or with numbers of CD34+VEGFR2+Lin- cells but they did correlate with numbers of CD4+ lymphocytes and NK cells. In conclusion, we have found that hematological patients have higher number of EC and lower numbers of CFU-En than healthy controls and that these parameters do not return to normal after short-term follow-up. Furthermore, our observations support emerging data that CFU-En represent cell population different from flowcytometrically defined EC and endothelial precursors and that their development requires cooperation of monocytes and CD4+ lymphocytes. However, cells forming CFU-En express endothelial surface markers and can contribute to proper endothelial function by NO production.     

紫杉醇联合重组人粒细胞集落刺激因子动员 乳腺癌患者外周血干细胞的效果及影响因素

 目的研究紫杉醇联合重组人粒细胞集落刺激因子（rhG-CSF）动员乳腺癌患者外周血干细胞（peripheral blood stem cell,PBSC）的效果及影响因素分析。方法2006年2月至2009年6月我科收治行紫杉醇动员的26例乳腺癌患者,紫杉醇（PTX,175 mg/m2 持续静脉滴注24 h）化疗后,白细胞降至1.0×109/L左右时使用rhG-CSF 5 μg /(kg·d) 动员至采集结束。并进一步分析患者年龄,化疗后白细胞最低数,采集前各类血细胞数,术后分期以及既往化疗等因素对采集单个核细胞（mononuclear cell,MNC）、CD34+细胞数的影响。结果白细胞计数于紫杉醇化疗后中位7d降至1.0×109/L 左右,皮下注射rhG-CSF中位4d进行外周造血干细胞采集,采集总MNC平均(7.89±1.45)×108/kg,采集总CD34+细胞平均(4.88±1.54)×106/kg。年龄与采集CD34+细胞数显著相关。而其他因素对MNC及CD34+细胞数均无显著影响（P>0.05）。所有患者均未出现严重不良反应。结论PTX（175 mg/m2 持续静脉滴注24h）联合rhG-CSF为转移性乳腺癌患者动员的有效安全方案。患者年龄显著影响CD34+细胞的采集数量。     

联合化疗加粒细胞集落刺激因素动员外周造血干细胞的作用

目的研究大剂量联合化疗(HDCT)加粒细胞集落刺激因子(G-CSF)对外周血造血干细胞的动员作用。方法8例非霍奇金淋巴瘤(NHL)多周期诱导化疗达完全缓解后,采用大剂量联合化疗,联合应用小剂量G-CSF进行外周造血干细胞的动员。结果动员后外周血WBC及MNC总数明显增加,与动员前比较,差异有显著性。冷冻前后,MNC计数、GFU-G集落总数无明显差异。预处理后,病人中性粒细胞、血小板恢复时间分别平均为(10.5±4)天及(11.5±6)天。结论大剂量联合化疗加小剂量G-CSF联合动员方案是安全有效的,值得推广。     

rHuG-CSF动员健康供者外周血造血干细胞的效果观察

目的:观察重组人粒细胞集落刺激因子(recombinant human granulocyte-colony stimulating factor,rHuG-CSF)动员健康供者外周血造血干细胞的效果及影响因素。方法:将本研究中心异基因造血干细胞移植健康供者163例,分别采用3种不同厂家生产的rHuG-CSF进行外周血造血干细胞动员,对其动员效果、受者移植后造血重建等情况进行比较。结果:不同种rHuG-CSF动员后采集的单个核细胞(MNC)及CD34 细胞均能满足临床造血干细胞移植的需要,130例人类白细胞抗原(human leucocyte antigens,HLA)配型相合的同胞受者移植后均获得顺利植入。动员的单个核细胞数及CD34 细胞数与性别无关,而CD34 细胞数在41~60岁年龄组中明显减少(P<0.05);对采集时机的分析显示:第5天采集的单个核细胞数及CD34 细胞数最高(P<0.05),此后逐渐下降。结论:糖基化的及两个非糖基化的rHuG-CSF制剂均能有效地在异基因移植中作为外周血造血干细胞动员剂。     

供者单采外周血中幼稚粒细胞检测的研究

目的 :探讨异基因外周血干细胞移植 ( Allo-PBSCT)供者经细胞集落刺激因子动员后 ,采集的外周血干细胞 ( PBSC)移植物中的幼稚粒细胞与单个核细胞 ( MNC)及 CD+ 3 4 细胞数之间相关性和移植的剂量标准。方法 :对 6例 Allo-PBSCT供者用 G-CSF或 G-CSF+GM-CSF进行动员 ,于动员前及动员后 ,对外周血及收集的MNC收集物中幼稚粒细胞及 CD+ 3 4 细胞进行检测计数 ,并计算出输给患者每公斤体重的 MNC、幼稚粒细胞及 CD+ 3 4细胞数。结果 :动员后外周血中的幼稚粒细胞与 CD+ 3 4 细胞数同步增加 ,外周血 MNC中幼稚粒细胞数与 CD+ 3 4 细胞数之间有较好的相关性。 6例患者全部植活恢复造血功能 ,并为染色体核型或血型转为供者型所证实。结论 :Allo-PBSCT供者经 G-CSF或 G-CSF+GM-CSF动员之后 ,外周血 MNC中幼稚粒细胞与 CD+ 3 4 细胞数有较好的相关性。因此 ,MNC与幼稚粒细胞数结合可作为 Allo-PBSCT的剂量标准 ,该法检测方便快速 ,稳定性好 ,便于推广     

A dose-finding study of glycosylated G-CSF (Lenograstim) combined with CHOP therapy for stem cell mobilization in patients with non-Hodgkin's lymphoma

BACKGROUND: Peripheral blood stem cell (PBSC) reinfusion has been widely used for hematopoietic reconstitution after high-dose chemotherapy. However, the optimal dose of granulocyte colony-stimulating factor (G-CSF) for PBSC mobilization in combination with chemotherapy for autograft remains unknown. METHODS: To find the optimal dose of glycosylated G-CSF (lenograstim) for PBSC mobilization in combination with chemotherapy for aggressive non-Hodgkin's lymphoma (NHL), we conducted a dose-finding study on 43 newly diagnosed patients who had unfavorable prognostic factors. They received four to six courses of cyclophosphamide, doxorubicin, vincristine and prednisolone combined with lenograstim every 2 weeks (biweekly CHOP therapy). PBSC apheresis was started after the third course of biweekly CHOP therapy. Lenograstim was given daily from day 3 until the day of the last apheresis. The optimum dose of lenograstim was assessed based on mobilization efficacy and safety profiles at a daily single dose of 2, 5 and 10 microg/kg for eight patients in each level. RESULTS: The collected number of CD34+ cells in the first apheresis products was higher in the 5 microg/kg group than in the 2 microg/kg group (median, 4.22 x 10(6) vs 2.49 x 10(6) CD34+ cells/kg, P = 0.051). The highest dose of 10 microg/kg (median, 2.99 x 10(6) CD34+ cells/kg) failed to show a dose dependence in PBSC mobilization. The efficacy and safety of the 5 microg/kg dose were further confirmed in an additional 19 patients. CONCLUSIONS: The present study suggests that the recommended dose of lenograstim for PBSC mobilization with CHOP therapy in untreated NHL is 5 microg/kg.     

Plerixafor and G-CSF for PBSC mobilization in patients with lymphoma who failed previous attempts with G-CSF and chemotherapy: a REL (Rete Ematologica Lombarda) experience

Plerixafor has been previously reported to improve PBSC collection in pts undergoing PBSC mobilization. Aim of the study was to assess the efficacy of plerixafor and G-CSF in pts with lymphoma who failed previous attempts of PBSC mobilization with conventional schemes of chemotherapy + G-CSF. 35 heavily pre-treated lymphoma pts (29 NHL, 6 HL) classified as “poor mobilizers” were enrolled in a program of compassionate use of plerixafor in 7 Italian centres of REL (Rete Ematologica Lombarda). Median number of previous lines of therapy was 3 and median number of previous attempts of mobilizations was 2. The median number of circulating CD34+ cells/μL following plerixafor was 11/μL. It was ≥10/μL in 17 pts and ≥20/μL in 10 pts; 13 were able to collect ≥2 × 10⁶ CD34+ cells/kg with a median of 1 apheresis procedure; 4 pts collected ≥4 × 10⁶ CD34+ cells/kg. A total of 6 pts had proceeded to transplant at the time of analysis. The median dose of PBSCs infused was 4 × 10⁶/kg and hematopoietic recovery was regular. In conclusion, plerixafor combined with G-CSF allows a collection of adequate number of PBSC in approximately 40% of cases of poor mobilizer, heavily pre-treated pts with lymphoma, who need consolidation with ASCT.     

超高CD34+采集的动员方案序贯二次自体造血干细胞移植治疗难治性 霍奇金淋巴瘤

目的:探讨超高CD34+采集的动员方案后序贯二次自体造血干细胞移植治疗难治性霍奇金淋巴瘤的疗效和安全性。方法:对1例经过多疗程一线、二线、新药、免疫等均难治的霍奇金淋巴瘤患者,予以IA+C方案化疗+G-CSF动员干细胞后采集出超高水平CD34+细胞,之后行自体造血干细胞移植,移植后获得完全缓解,再予序贯第二次自体造血干细胞移植进行巩固治疗。结果:总计输注单个核细胞数13.67×108/kg,CD34+细胞48.68×106/kg,第一次自体造血干细胞移植术后第7天造血功能恢复,复查全身PET-CT提示获得完全缓解,第二次自体造血干细胞移植术后第8天造血功能恢复,两次自体造血干细胞移植相关并发症均在可控范围内。结论:超高CD34+细胞采集的IA+C方案化疗+G-CSF动员可以让患者有机会进行多次自体造血干细胞移植,是临床动员的创新方案。对于难治性霍奇金淋巴瘤,序贯二次自体造血干细胞移植可达到更深层次缓解,且安全性较高,延长患者无疾病生存期及总生存期,为难治性霍奇金淋巴瘤治疗提供更多临床依据。     

改良CVP联合rhG—CSF动员方案外周血干细胞移植治疗血液肿瘤及实体瘤41例

目的：研究改良CVP联合rhG—CSF方案对血液肿瘤和实体瘤41例患者自体外周血干细胞移植（APBSCT）动员及造血重建效果。方法：2001年3月至2006年3月采用改良CVP联合rhG—CSF动员方案，完成APBSCT41例（血液肿瘤32例，实体瘤9例），平均年龄39．6岁（18岁～67岁）。WBC升至4．0×10^9／L左右采集单个核细胞（MNC）并计数MNC和CD34^＋细胞数；预处理结束48h～72h回输MNC。结果：动员期间患者WBC均降至1．0×10^9／L以下，PLT 40×10^9以下。34例1次采集成功，7例（双次移植5例）作第2次采集。采集MNC数0．9×10^8／kg～8．3×10^8／kg（2．8±2．0×10^8／kg），CD34^＋细胞1．1×10^6／kg～9．4×10^6／kg（3．2±2．6×10^6／kg）。预处理后所有病例均达到骨髓抑制，WBC恢复到1．0×10^9／L时间为＋8～＋16d（平均＋11．3d）；38例PLT恢复到50×10^9／L时间为＋13～＋22d（平均＋16．8d），3例P1月恢复延迟，最长＋35d。随访15～65个月，持续完全缓解19例（46．3％），部分缓解或好转13例（31．7％），总有效率78．0％，无效9例（22．0％），无1例发生移植相关死亡（其中5例带瘤生存，17例死亡）。结论：改良CVP联合rhG—CSF动员方案行APBSCT是一种安全有效的动员自体外周血造血干细胞的方法，临床疗效满意。     

Hematopoietic stem cell mobilization strategies to support high-dose chemotherapy: A focus on relapsed/refractory germ cell tumors

High-dose chemotherapy (HDCT) with autologous hematopoietic stem cell transplantation has been explored and has played an important role in the management of patients with high-risk germ cell tumors (GCTs) who failed to be cured by conventional chemotherapy. Hematopoietic stem cells (HSCs) collected from the peripheral blood, after appropriate pharmacologic mobilization, have largely replaced bone marrow as the principal source of HSCs in transplants. As it is currently common practice to perform tandem or multiple sequential cycles of HDCT, it is anticipated that collection of large numbers of HSCs from the peripheral blood is a prerequisite for the success of the procedure. Moreover, the CD34+ cell dose/kg of body weight infused after HDCT has proven to be a major determinant of hematopoietic engraftment, with patients who receive > 2 × 10⁶ CD34+ cells/kg having consistent, rapid, and sustained hematopoietic recovery. However, many patients with relapsed/refractory GCTs have been exposed to multiple cycles of myelosuppressive chemotherapy, which compromises the efficacy of HSC mobilization with granulocyte colony-stimulating factor with or without chemotherapy. Therefore, alternative strategies that use novel agents in combination with traditional mobilizing regimens are required. Herein, after an overview of the mechanisms of HSCs mobilization, we review the existing literature regarding studies reporting various HSC mobilization approaches in patients with relapsed/refractory GCTs, and finally report newer experimental mobilization strategies employing novel agents that have been applied in other hematologic or solid malignancies.     

CTX、G-CSF 动员造血干细胞过程中NK 细胞检测

 目的　探讨环磷酰胺 ( CTX)、粒细胞集落刺激因子 ( G- CSF)动员癌症患者造血干细胞过程中 NK细胞数量和活性的变化。方法　 2 1例诊断明确的癌症患者 ,经 CTX4.0 g/m2和 G- CSF(惠尔血 ) 1 5 0 μg/d动员。动员前 (前期 )、WBC降至最低点时 (极期 )、WBC开始恢复后 3天 (恢复早期 )、WBC开始恢复后 6天 (恢复期 )用流式细胞仪计数 CD34 +细胞和 NK细胞 ,用乳酸脱氢酶释放法测量 NK细胞活性。结果　动员过程中 ,NK细胞极期显著低于前期 ,恢复期则显著高于前期 ,P<0 .0 1 ;其变化与 WBC、MNC、血小板 ( BPC)、CD34 + 细胞呈显著正相关 ,P<0 .0 5。 NK细胞活性无显著差别 ,P>0 .0 5。结论　动员过程中 NK细胞数量增加 ,活性无改变。