A dose-finding study of lenograstim (glycosylated rHuG-CSF) for peripheral blood stem cell mobilization during postoperative adjuvant chemotherapy in patients with breast cancer. Lenograstim/Breast Cancer Study Group.

BACKGROUND: The optimum dose of granulocyte colony-stimulating factor (G-CSF) for peripheral blood stem cell (PBSC) mobilization after disease-oriented, conventional-dose chemotherapy remains unknown. METHODS: A multicenter dose-finding study of glycosylated G-CSF (lenograstim) for the mobilization of PBSCs following adjuvant CAF chemotherapy (cyclophosphamide, doxorubicin and 5-fluorouracil) was performed in 38 patients with postoperative breast cancer. Each 10, ten and eight patients were sequentially allocated to one of the three dose groups (2, 5 and 10 micrograms/kg, respectively) of lenograstim. Lenograstim was administered subcutaneously (s.c.) daily from day 8 to the day of the last apheresis and CD34+ cells and colony-forming units-granulocyte macrophage (CFU-GMs) in peripheral blood were measured serially. Additionally, 10 patients who received adjuvant CAF chemotherapy alone also participated in the study, as a control. RESULTS: Lenograstim was well tolerated up to 10 micrograms/kg, except for one patient given 10 micrograms/kg who developed transient grade 3 hepatic enzyme elevation. The peak levels of CD34+ cells and CFU-GMs in peripheral blood showed dose-response relationships. The median peak CD34+ cells for the 0, 2, 5 and 10 micrograms/kg dose groups were 5.4, 34.3, 55.0 and 127.6 cells/microliter, respectively, and those of CFU-GMs for the 0, 2, 5 and 10 micrograms/kg dose groups were 0.01, 0.33, 1.32 and 3.30 CFU-GMs/microliter, respectively. CONCLUSIONS: Considering the previous reports suggesting that a pre-apheresis number of 40-50 CD34+ cells/microliter in peripheral blood is highly predictive for achievement of more than 2.5 x 10(6) CD34+ cells/kg in a standard apheresis procedure of 10 litres, the optimum dose of lenograstim for PBSC mobilization following CAF chemotherapy in patients with postoperative breast cancer is 5 micrograms/kg/day s.c.     

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.     

化疗联合单一剂量rhG-CSF用于自体外周血造血干细胞移植的临床研究

背景与目的:总结广东省干细胞多中心研究协作组自1999年6月至2001年12月间55例自体外周血造血干细胞移植治疗造血系统恶性疾病的资料,对化疗联合单一剂量rhG-CSF用于自体外周血造血干细胞移植前动员及移植后造血重建的效果进行研究和评价。方法:全部病例(急性髓细胞性白血病28例,急性淋巴细胞性白血病9例,非霍奇金淋巴瘤14例,其他4例)采用化疗+重组粒系集落刺激因子(rhG-CSF,格拉诺赛特)联合动员方案,其中白血病患者主要采用EA方案,恶性淋巴瘤患者主要采用以CTX为主的方案。rhG-CSF用量为250μg/d,WBC升至>4×109/L后,连续1～2天采集PBSC。移植后+3天开始使用rhG-CSF250μg/d,并观察造血重建情况。结果:动员所需的时间即自化疗开始至采集的平均时间为(18.08±3.63)天,rhG-CSF平均应用剂量为4.15μg·(kg·d)-1,应用时间平均7.12天。55例患者平均采集1.38次,采集到的MNC细胞数为(4.09±1.69)×109/kg,CD34+细胞平均值为8.5×106/kg,CFU-GM平均为(6.1±5.8)×105/kg。WBC恢复至>1.0×109/L及中性粒细胞绝对值>0.5×109/L的中位天数分别为10天和10.5天,全部移植患者均获满意的造血重建。结论:我们采用的EA和以CTX为主的化疗联合单一剂量rhG-CSF,是一种安全有效的动员自体外周血造血干细胞的方法,单一剂量rh     

Age has no influence on mobilization of peripheral blood stem cells in acute myeloid leukemia

The upper age limit for autologous stem cell transplantation (ASCT) in acute myeloid leukemia (AML) is increasing and peripheral blood (PB) represents the standard source of stem cell (SC). However, no data are available on the impact of age on SC mobilization in AML. We analyzed a cohort of 150 consecutive AML patients in first complete remission in order to make a comparison between patients up to 60 years and above 60 years, by evaluating CD34+ cells mobilization into PB and the number of leukapheresis needed to collect at least one single SC graft. The successful mobilization rate (>2 x 10(6) CD34+ cells/kg) was comparable between the two groups (87% vs. 80%, p = 0.29). In addition, no statistically significant difference was found in terms of either median number of CD34+ cells collected (p = 0.54) or CD34+ cells peak in PB (p = 0.70). Both groups of patients needed a median of two apheresis and no difference was found in the median number of CD34+ cells collected per single apheresis (p = 0.67). Finally, no correlation was found between age and total number of CD34+ cells collected (r = 0.003, p = 0.58). We conclude that age has no impact on mobilization of PBSCs in AML.     

Efficacy of the mobilization of peripheral blood stem cells by granulocyte colony-stimulating factor in pediatric donors.

The advantages/disadvantages of the use of peripheral blood stem cells (PBSCs) for allogeneic transplantation still need to be clarified, particularly in children. We compared the kinetics, efficacy, and safety of PBSC mobilization by granulocyte colony-stimulating factor (G-CSF) and collection by apheresis between healthy pediatric and adult donors. A total of 19 pediatric (median age, 6 years) and 25 adult healthy donors (median age, 37 years) were given 10 micro/kg/day of G-CSF for 5 consecutive days for PBSC mobilization, which were harvested by apheresis on days 5 and/or 6. All of the donors tolerated the whole procedures. Serum trough levels of G-CSF determined by ELISA were significantly lower in the 16 pediatric donors evaluated than in adults (n = 16) on days 3 and 4 (P < 0.05). Although the WBC counts on days 4 and 5 were significantly higher in adults than in children (P = 0.006 and 0.004, respectively), the numbers of circulating CD34+ cells/unit of blood were identical. The number of blood CD34+ cells collected per unit of blood processed was identical in both donor populations. We propose that PBSCs could be effectively mobilized and collected in small children so that they could be donors for adult patients.     

High-versus standard-dose filgrastim (rhG-CSF) for mobilization of peripheral-blood progenitor cells from allogeneic donors and CD34(+) immunoselection.

PURPOSE: The efficacy of a high- versus a standard-dose filgrastim (recombinant human granulocyte colony-stimulating factor, or rhG-CSF) regimen to mobilize peripheral-blood progenitor cells (PBPCs) for allogeneic transplantation was investigated in 75 healthy donors. PATIENTS AND METHODS: From December 1994 to December 1997, 75 consecutive donors (median age, 38 years; range, 17 to 67 years) were assigned to two different schedules of rhG-CSF for PBPC mobilization. Fifty donors received 24 microg rhG-CSF/kg body weight (BW) divided into two daily subcutaneous injections (two doses of 12 microg, group A), whereas 25 were treated with 10 microg rhG-CSF once daily (group B). Apheresis was started on day 4 in group A and on day 5 in group B. Target CD34(+) cell numbers in apheresis products were >/= 4 x 10(6)/kg recipient BW. RESULTS: Cytokine priming and collection of PBPCs were equally well tolerated in both groups. Significantly higher CD34(+) cell numbers in group A with 3. 7 x 10(6)/kg recipient BW/apheresis (0.47 x 10(6)/L apheresis) compared with 2 x 10(6)/kg recipient BW/apheresis (0.25 x 10(6)/L apharesis) in group B were obtained (P <.05). Using standard aphereses (median, 9 L), two doses of 12 microg rhG-CSF/kg allowed collection of >/= 4 x 10(6)/kg CD34(+) cells with two aphereses (range, one to three) in group A versus three aphereses (range, one to six) in group B (P <.015). Donor age, sex, and BW influenced the collection of CD34(+) cell numbers: in particular, significantly higher apheresis results were obtained in donors younger than 40 years compared with donors older than 40 years of age (P <.05). In 65 CD34(+) selection procedures using avidin-biotin immunoabsorption columns (Ceprate SC System, CellPro, Bothell, WA), a median CD34(+) purity of 53%, CD34(+) recovery of 40%, and the collection of 2 x 10(6)/kg CD34(+) cells/selection were achieved. In group A with higher CD34(+) cells/kg/apheresis, CD34(+) purity, recovery, and cell yields were 60%, 45%, and 2.3 x 10(6)/kg/selection, respectively, as compared with 48%, 31%, and 0.7 x 10(6)/kg in group B (P <.05). CONCLUSION: Our results demonstrate that twice daily rhG-CSF (two doses of 12 microg/kg BM) compared with once daily rhG-CSF (10 microg/kg BW), in addition to being well tolerated, significantly improves PBPC mobilization, allows the collection of higher numbers of CD34(+) cells with one or two standard aphereses, and facilitates subsequent selection procedures in healthy allogeneic donors.     

Sequential analysis of CD34+ and CD34- cell subsets in peripheral blood and leukapheresis products from breast cancer patients mobilized with SCF plus G-CSF and cyclophosphamide.

Administration of stem cell factor (SCF) has been proven to enhance cytokine-induced mobilization of CD34+ hematopoietic progenitor cells (HPC) into the peripheral blood (PB). The aim of the present study was to explore in a homogeneous group of 22 uniformly treated breast cancer patients: (1) the kinetics of mobilization into PB of both CD34+ and CD34- cell subsets, including dendritic cells, in sequential samples obtained from day +7 up to day +12 after mobilization; and (2) the composition of the CD34+ and CD34- cell subsets present in the two leukapheresis products obtained for each patient. The following CD34+ and CD34- subsets were analyzed: early CD34+ HPC, erythroid-, myeloid- and B-lymphoid-committed CD34+ precursor cells, mature T, B and NK cells, monocytes, neutrophils, eosinophils, basophils, and dendritic cells (DC) including three subsets of lin-/HLADR+DC (CD16+, CD33high and CD123high). Our results show that the absolute number of PB CD34+ HPC progressively increases from day +7 onwards. As far as the CD34- PB leukocyte subsets are concerned, monocytes (CD14+) displayed the earliest recovery after mobilization predicting neutrophil recovery 1 day in advance. The number of CD34+ HPC collected in a single leukapheresis product was always > or = 1.4 x 10(6) cells/kg body weight. No significant changes were observed between the two leukapheresis sessions either as regards their composition in CD34+ HPC subsets or their CD34- leukocyte populations except for a higher ratio of both CD34+ erythroid/CD34+ myeloid HPC (0.35 +/- 0.13 vs 0.30 +/- 0.13; P = 0.04) and neutrophils/monocytes (1.58 +/- 2.1 vs 0.69 +/- 0.27; P = 0.009) found for the first leukapheresis. Interestingly, the overall number of dendritic cells (DC) was higher in the second leukapheresis (1.06 +/- 0.56 vs 1.9 +/- 0.46; P = 0.02) due to a selective increase of the CD16+ antigen-presenting cells. In summary, our results show that the combination of cyclophosphamide, G-CSF and SCF is highly effective for stem cell mobilization, with differences observed in the mobilization kinetics of the different hematopoietic cell subsets analyzed.     

Successful mobilization of Ph-negative blood stem cells with intensive chemotherapy + G-CSF in patients with chronic myelogenous leukemia in first chronic phase

The aim of the study was to investigate the feasibility of mobilizing Philadelphia chromosome negative (Ph-) blood stem cells (BSC) with intensive chemotherapy and lenograstim (G-CSF) in patients with CML in first chronic phase (CP1). During 1994-1999 12 centers included 37 patients <56 years. All patients received 6 months' IFN, stopping at median 36 (1-290) days prior to the mobilization chemotherapy. All received one cycle of daunorubicin 50 mg/m2 and 1 hour infusion on days 1-3, and cytarabine (ara-C) 200 mg/m2 24 hours' i.v. infusion on days 1-7 (DA) followed by G-CSF 526 microg s.c. once daily from day 8 after the start of chemotherapy. Leukaphereses were initiated when the number of CD 34+ cells was >5/microl blood. Patients mobilizing poorly could receive a 4-day cycle of chemotherapy with mitoxantrone 12 mg/m2/day and 1 hour i.v infusion, etoposide 100 mg/m2/day and 1 hour i.v. infusion and ara-C 1 g/m2/twice a day with 2 hours' i.v infusion (MEA) or a second DA, followed by G-CSF 526 microg s.c once daily from day 8 after the start of chemotherapy. Twenty-seven patients received one cycle of chemotherapy and G-CSF, whereas 10 were mobilized twice. Twenty-three patients (62%) were successfully (MNC >3.5 x 10(8)/kg, CFU-GM >1.0 x 10(4)/kg, CD34+ cells >2.0 x 10(6)/kg and no Ph+ cells in the apheresis product) [n = 16] or partially successfully (as defined above but 1-34% Ph+ cells in the apheresis product) [n = 7] mobilized. There was no mortality during the mobilization procedure. Twenty-one/23 patients subsequently underwent auto-SCT. The time with PMN <0.5 x 10(9)/l was 10 (range 7-49) and with platelets <20 x 10(9)/l was also 10 (2-173) days. There was no transplant related mortality. The estimated 5-year overall survival after auto-SCT was 68% (95% CI 47 - 90%), with a median follow-up time of 5.2 years.We conclude that in a significant proportion of patients with CML in CP 1, intensive chemotherapy combined with G-CSF mobilizes Ph- BSC sufficient for use in auto-SCT.     

联合化疗加重组人粒细胞集落刺激因子动员自体外周血干细胞

目的观察环磷酰胺(CTX)为主的联合化疗加重组人粒细胞集落刺激因子(rhG-CSF)对自体外周血干细胞(APBSC)的动员效果。方法CTX（2.5±1.0）g/m     

Comparison of lenograstim vs filgrastim administration following chemotherapy for peripheral blood stem cell (PBSC) collection: a retrospective study of 126 patients

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.     

Mobilization of peripheral blood progenitor cells with a combination of cyclophosphamide, r-metHuSCF and filgrastim in patients with breast cancer previously treated with chemotherapy.

The objective of our study was to determine the effect of adding r-metHuSCF to Filgrastim and cyclophosphamide for mobilization of peripheral blood progenitor cells (PBPC), on collection of CD34(+) cells and engraftment after autologous stem cell transplant. Twenty-three patients with previously treated stage II-IV breast cancer received cyclophosphamide (3 g/m(2)), Filgrastim 5 microg/kg daily and r-metHuSCF 20 microg/kg daily. Two PBPC collections were performed on consecutive days starting the day the WBC count was above 7.5 x 10(3)/microl. Collection was performed between days +9 and +12 and the median number of CD34(+) cells collected was 9.9 x 10(6)/kg (1.1-53.1) and 6.6 x 10(6)/kg (1.4-33.8) for the first and second apheresis, respectively. Despite being previously treated patients, the target CD34(+) cell dose required for SCT was obtained in all patients. SCT was associated with rapid neutrophil and platelet engraftment and a highly significant correlation was observed between the number of CD34(+) cells infused and engraftment. Treatment with SCF plus filgrastim was well tolerated, with mild to moderate local skin rash being the most frequently reported adverse event. In conclusion, addition of r-metHuSCF induces mobilization of a large number of CD34(+) cells which results in shortening of time to engraftment and hospitalization.     

The stem cell mobilizing capacity of patients with acute myeloid leukemia in complete remission correlates with relapse risk: results of the EORTC-GIMEMA AML-10 trial.

Variable numbers of CD34+ cells can be harvested from the blood of AML patients in CR after G-CSF supported mobilization following consolidation chemotherapy. We hypothesized that a decreased ability to mobilize stem cells reflects a chemotherapy-induced reduction in the number of normal and leukemic stem cells. We therefore analyzed whether the mobilizing capacity of these patients was of prognostic significance. 342 AML-patients in first CR received daily G-CSF from day 20 of the consolidation course and underwent 1-6 aphereses to obtain a minimum dose of 2 x 10(6) CD34+ cells/kg. Afterwards they were randomized for autologous bone marrow (BM) or blood SCT. As a surrogate marker for the mobilizing capacity, the highest yield of CD34+ cells of a single apheresis was adopted. Patients could be categorized into four groups: no harvest (n = 76), low yield (<1 x 10(6) CD34+/kg; n = 50), intermediate yield (1-6.9 x 10(6) CD34+ cells/kg; n = 128) and high yield (> or = 7 x 10(6) CD34+ cells/kg; n = 88). The median follow-up was 3.4 years; 163 relapses and 16 deaths in CR were reported. Autologous blood or BM SCT was performed in 36%, 64%, 81% and 88%, respectively, of the patients assigned to the no harvest, low, intermediate and high CD34+ yield group. The 3-year disease-free survival rate was 46.7%, 65.0%, 50.4% and 26.9% (P = 0.0002) and the relapse incidence was 47.5%, 30.1%, 43.1% and 71.9% (P < 0.0001). Multivariate Cox's proportional hazards model showed that the CD34+ yield was the most important independent prognostic variable (P = 0.005) after cytogenetics. Patients with the highest mobilizing capacity have a poor prognosis due to an increased relapse incidence.     

单一剂量G-CSF用于异基因外周血造血干细胞动员和移植后造血恢复的临床研究

背景与目的:应用粒系集落刺激因子(granulocytecolony-stimulatingfactor,G-CSF)等动员剂从健康供者中动员和获取造血干细胞用于异基因外周血造血干细胞移植(allogeneicperipheralbloodstemcelltransplantation,allo-PBSCT)已在临床广泛开展,但在其作用机理、给药剂量和给药方案等方面还存在许多问题有待进一步研究。本研究旨在探讨单一剂量的G-CSF(250μg/d)用于allo-PBSCT的外周血干细胞(peripheralbloodstemcell,PBSC)动员以及移植后造血恢复的安全性和有效     

Late afternoon dosing of plerixafor for stem cell mobilization: a practical solution

BackgroundPlerixafor was recently approved for stem cell mobilization in patients who have non-Hodgkin lymphoma or multiple myeloma. However, the use of late evening (10 PM) injections is inconvenient for patients and requires an after-hours infrastructure that may not be readily available.Patients and MethodsBased on an earlier study showing prolonged mobilization of stem cells in patients given plerixafor plus granulocyte colony-stimulating factor (G-CSF), we administered plerixafor at 5 PM and performed apheresis approximately 15 hours later. Plerixafor was administered primarily to patients who either had failed previous mobilization or were at risk for poor mobilization because of previous therapy, especially lenalidomide in patients who had multiple myeloma.ResultsOf 48 patients, including 24 with myeloma and 24 with lymphoma, 47 had enough stem cells collected (> 2 × 10E6 CD34+ cells/kg) to proceed to transplant, including all 13 patients who had failed previous chemotherapy plus G-CSF mobilization and 18 patients treated with four cycles or more of lenalidomide. The day +1 post-plerixafor increment in circulating CD34+ cells was greatest in patients who had the highest preplerixafor CD34 count; however, in patients with preplerixafor CD34+ cell counts < 10/μL (and who typically mobilize poorly), 83% of patients had enough stem cells collected to proceed to transplant.ConclusionThis study suggests that plerixafor is effective when given 15 hours before apheresis, even in a population at high risk for mobilization failure. A proposed cost-effective use of plerixafor is to administer it to patients who are inadequately mobilized with G-CSF alone or for salvage in patients who fail previous mobilization with chemotherapy plus G-CSF.     

Prophylactic growth factor-primed donor lymphocyte infusion using cells reserved at the time of transplantation after allogeneic peripheral blood stem cell transplantation in patients with high-risk hematologic malignancies

BACKGROUND: Standard allogeneic bone marrow transplantation (BMT) offers only a small chance of cure for most adult patients with advanced hematologic malignancies. The authors postulated that allogeneic peripheral blood stem cell transplantation (PBSCT) followed by prophylactic growth factor-primed donor lymphocyte infusion (DLI) with cells reserved at harvest would maximize the graft-versus-tumor effects in patients with hematologic malignancies who had a high risk of recurrence. METHODS: Seventeen patients with hematologic malignancies who had a high risk of recurrence were allocated on an intent-to-treat basis to allogeneic PBSCT from human leukocyte antigen-matched sibling donors followed by prophylactic growth factor-primed DLI of cells reserved at harvest for transplantation. RESULTS: The median age was 37 years (range, 19-56 years). All donors underwent two or more apheresis procedures. The median numbers of mononuclear cells (MNCs), CD34 positive (CD34+) cells, and CD3+ cells, respectively, that were collected for 17 donors were 9.0 x 10(8) MNCs/kg (range, 4.9-14.4 x 10(8) MNCs/kg), 13.0 x 10(6) CD34+ cells/kg (range, 2.4-75.2 x 10(6) CD34+ cells/kg), and 5.8 x 10(8) CD3+ cells/kg (range, 3.3-9.9 x 10(8) CD3+ cells/kg) for a mean number of 2.35 apheresis procedures (range, 2.0-4.0 procedures). The median numbers of MNCs and CD3+ cells that were cryopreserved were 2.1 x 10(8) MNCs/kg (range, 0.0-4.4 x 10(8) MNCs/kg) and 1.4 x 10(8) CD3+ cells/kg (range, 0.0-3.5 x 10(8) CD3+ cells/kg). Seven of 17 patients received additional PBSCs, with a median of 5.0 x 10(7) CD3+ cells/kg (range, 3.0-9.9 CD3+ cells/kg) between Day 41 and Day 120. The reasons for inability to administer additional PBSCs in 10 patients included early death (n = 4 patients), severe graft-versus-host disease (GVHD) (n = 3 patients), disease recurrence (n = 2 patients), and harvest failure (n = 1 patient). Of seven patients, two patients died of recurrence, and one died of cytomegalovirus pneumonitis. The surviving four patients were free of disease when last assessed (median follow-up, 597 days) but were suffering from chronic GVHD (one patient had limited GVHD, and three patients had extensive GVHD). CONCLUSIONS: The authors suggest that allogeneic PBSCT with prophylactic growth factor-primed DLI may be a potentially curative strategy for the treatment of hematologic malignancies in patients with a high risk of recurrence. Their approach may offer the additional advantage of collecting enough cells at harvest for the potential use of DLI, which is easy, convenient for donors, and cost effective.     

急性白血病异基因外周血造血干细胞移植血缘供者安全性分析

目的：探讨急性白血病异基因外周血造血干细胞移植血缘供者近期的不良事件及远期的安全性。方法185例急性白血病异基因外周血造血干细胞移植血缘供者,干细胞动员后,用COBE Spectra血细胞分离机采集外周血干细胞。检测供者动员时血常规及形态学分类、CD34＋细胞百分比、干细胞混悬液中单个核细胞（ MNC）数量及CD34＋细胞计数,同时记录供者动员和采集过程中的不良事件、采集后第1、3、7天血常规变化及长期随访。结果血缘供者干细胞动员前白细胞计数为（6.16±1.58）x 109·L-1,采集时白细胞计数为（41.55±9.77）x109·L-1,是动员前6.75（4.18-10.87）倍。干细胞混悬液MNC为（247.61±105.99）x 108,CD34＋细胞为（3.54±3.42）x 108。动员时血缘供者的常见不良事件有头痛、腰背困痛、四肢痛、全身痛,合计占94.6%;外周血干细胞采集过程中,静脉持续输注葡萄糖酸钙,供者口周和指尖麻木等低钙症状发生率为3.2%;所有供者的不良事件均可耐受,无一例供者因不良事件终止干细胞动员或采集。供者干细胞采集后1周血象基本恢复正常;随访11 a血缘供者健康状况良好,无与动员及采集相关的远期并发症发生。结论急性白血病异基因外周血造血干细胞移植血缘供者动员采集无明显的近期不良事件及远期并发症,安全性非常高,为非血缘移植供者提供可靠的安全保障依据,减少恐惧感,降低反悔率。     

环磷酰胺或足叶乙甙联合粒细胞集落刺激因子动员自体外周血造血干细胞的对照研究

背景与目的:通过动员采集获得高质量的自体外周血造血干细胞(autologousperipheralbloodstemcell,APBSC)是造血干细胞移植成功的关键,环磷酰胺(cyclophosphamide,CTX)联合重组人粒细胞集落刺激因子(recombinedhumangranulocytecolony-stimulatingfactor,rhG-CSF)是APBSC经典的动员方案,足叶乙甙(etoposide,VP-16)联合rhG-CSF是近年来应用的另一个动员方案。本研究的目的是比较上述两种动员方案对恶性淋巴瘤和生殖细胞肿瘤患者APBSC的动员效果。方法:共有52例恶性实体瘤患者,其中CTX方案组26例,剂量为CTX3.5g/m2加rhG-CSF5μg·kg-1·d-1;VP-16方案组26例,VP-16的剂量随机采用1000mg/m2或1500mg/m2加rhG-CSF5μg·kg-1·d-1。两组均在白细胞(whitebloodcell,WBC)降至最低点时开始皮下注射rhG-CSF,直至采集结束前一天。当CTX组WBC恢复到2.5×109/L、VP-16组WBC恢复到5.0×109/L以上时开始连日采集APBSC,当累计采集的单个核细胞(mononuclearcell,MNC)≥5×108/kg或CD34+细胞≥2×106/kg时停止采集。患者经预处理后回输采集到的APBSC。比较两组动员采集过程中的血液学指标变化、采集细胞数量、造血重建时间、不良反应等。结果:CTX组患者化疗后外周血中WBC和血小板(platelet,PLT)降至最低值的时间明显早于VP-     

ESHAP and G-CSF is a superior blood stem cell mobilizing regimen compared to cyclophosphamide 1.5 g m(-2) and G-CSF for pre-treated lymphoma patients: a matched pairs analysis of 78 patients

Cyclophosphamide 1.5 g m(-2) followed by granulocyte colony-stimulating factor (G-CSF) is an effective peripheral blood stem cell (PBSC) mobilizing regimen, but has limited anti-lymphoma activity. We therefore assessed the mobilizing potential of ESHAP (etoposide, ara-C, methylprednisolone and cisplatin), a potent second-line lymphoma regimen followed by G-CSF. The results were compared in 78 patients with relapsed or resistant lymphomas with the use of cyclophosphamide 1.5 g m(-2) followed by G-CSF in a matched pairs analysis, matching the ESHAP recipients (for predetermined prognostic factors) from a cohort of 178 lymphoma patients mobilized with cyclophosphamide and G-CSF. The total numbers of mononuclear cells collected at apheresis was similar with both regimens but ESHAP plus G-CSF resulted in a significantly higher percentage of CD34+ cells, absolute number of CD34+ cells and GM-CFC (all with P-values < 0.001). The number of patients requiring only one apheresis harvest to achieve a CD34+ cell yield of > 2.0 x 10(6) kg(-1) was greatly increased in the ESHAP recipients (56/78 vs 17/78, P < 0.001). The total number of progenitor cells collected was not significantly different with the two mobilization regimens because of this higher number of apheresis in the cyclophosphamide group. The proportion of patients who failed to achieve a minimum CD34+ cell target of 1 x 10(6) kg(-1) with the pooled harvests was less in the ESHAP arm (four patients vs nine patients) despite an increased number of aphereses in the cyclophosphamide recipients. ESHAP plus G-CSF is well tolerated and is an excellent mobilization regimen in patients with pre treated lymphoma.     

多西他赛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分析

 目的研究多西他赛联合重组人粒细胞集落刺激因子（rhG-CSF）在乳腺癌患者动员外周血干细胞 （peripheral blood stem cell,PBSC）的效果及影响因素。方法2006年2月—2009年6月我科收治的55例 行多西他赛（商品名多帕菲,TXT,120 mg/m2 持续静脉滴注3 h）动员的乳腺癌患者,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、内脏、骨转移情况及化、放疗情况对采集单个核细胞（mononuclear cell,MNC）和CD34+细胞的影响。结果多西他赛化疗动员后中位7d白细胞降至1.0×109/L 左右,皮下注 射rhG-CSF中位3d,采集总MNC平均(5.51±1.24)×108/kg,采集总CD34+细胞平均(2.90±1.38)×106/kg 。年龄、化疗后白细胞最低数与采集CD34+细胞均显著相关（P<0.05）。化疗的周期数≤6的患者采集平均 CD34+细胞数较周期数≥6患者显著增高（P<0.05）。无1例患者出现严重不良反应。结论TXT（120 mg/m2 持续静脉滴注3 h）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、既往化疗周期数显 著影响患者CD34+细胞的采集数量。患者化疗后白细胞最低数可作为采集CD34+细胞数量的预测指标。     

非血缘异基因外周血造血干细胞动员与采集的效果及安全性评价

目的 评价非血缘异基因外周血造血干细胞动员与采集的效果及安全性.方法 按照中华造血干细胞资料库制定的非血缘异基因干细胞动员方案,结合移植医院的动员要求及捐献者的体质情况制订合理的干细胞动员方案,对山西医科大学第二医院2012年5月至2017年1月行非血缘异基因外周血造血干细胞采集的64名健康供者,采用动员剂粒细胞集落刺激因子(G-CSF)5～10μg·kg-1·d-1,单次或分次皮下注射,3～4 d后使用COBE Spectra血细胞分离机进行外周血造血干细胞采集.对不同年龄、性别供者的动员、采集效果及不良反应进行分析.结果3 d或4 d动员方案均可达到采集要求,采集的单个核细胞数≥5.0×108/kg,CD34阳性细胞数≥2.0×106/kg.单次采集成功率(采集的单个核细胞及CD34阳性细胞数达标)为65％,采集效率为52％,可降低患者费用及供者的风险.年轻、体质好的供者采集的干细胞质量高于年龄偏大者.16名(25％)供者出现轻度不良反应,无需特殊处理.结论非血缘异基因干细胞动员、采集是安全的.从节省医疗资源、更多关注供者利益出发,采用3 d或4 d动员方案提高单次采集成功率是可行的.采集过程中应做好供者低血钙症状的观察并给予相应的健康教育,以缓解供者的紧张情绪.