Hematopoietic colony-stimulating factors for neutropenic patients in the ICU

OBJECTIVE: To assess whether adjunct hematopoietic colony-stimulating factor (H-CSF) accelerates neutrophil recovery and improves survival. DESIGN: A retrospective study. SETTING: Medical/surgical intensive care unit (ICU). PATIENTS: 30 neutropenic patients admitted to the ICU and treated with H-CSF. Controls were the preceding 30 neutropenic patients not treated with H-CSF. MEASUREMENTS AND RESULTS: Patient admission characteristics were reviewed. Endpoints were neutrophil recovery ( > 1.0 x 10(9)/l), length of ICU stay and survival. Depth and duration of neutropenia (0.267 +/- 0.04 x 10(9)/l for 12 +/- 1.7 days vs 0.293 +/- 0.05 x 10(9)/l for 15 +/- 1.9 days; p = 0.67 and 0.21), and the Acute Physiology and Chronic Health Evaluation II and organ system failure scores were similar. Systemic candidiasis was lower in the H-CSF group (20 vs 3 %; p > 0.05). In 11 (36.6 %) and 10 (33.3 %) patients neutrophil count recovered ( > 1.0 x 10(9)/l); H-CSF did not reduce the duration of neutropenia (7.8 +/- 1.4 vs 5.7 +/- 1.3 days; p = 0. 28), the length of ICU stay (7.8 +/- 1.1 vs 8.9 +/- 1.5 days; p = 0. 55) or improve survival (23 vs 10 %; p = 0.168). CONCLUSION: H-CSF for treatment of neutropenia in patients admitted to the ICU did not accelerate neutrophil recovery or improve survival.     

CD34+ cell dose requirements for rapid engraftment in a sequential high-dose chemotherapy regimen of paclitaxel, melphalan, and cyclophosphamide, thiotepa, and carboplatin (CTCb) with PBPC support in metastatic breast cancer

Sequential high-dose chemotherapy may increase the threshold dose of CD34+ cells necessary for rapid and successful hematologic recovery. There are limited data regarding the pharmacodynamics and threshold CD34+ cell dose required for engraftment following high-dose paclitaxel. To determine the dose of CD34+ PBPC sufficient for rapid engraftment, 65 women with metastatic breast cancer undergoing a sequential high-dose paclitaxel, melphalan, and cyclophosphamide, thiotepa, and carboplatin (CTCb) chemotherapy regimen were evaluated. The intertreatment interval was a median of 27 days. Paclitaxel was escalated from 400 to 825 mg/m2, infused continuously (CI) over 24 h on day -4 with PBPC reinfusion on day 0. Following marrow recovery, 90 mg/m2/day of melphalan was given over 30 min on days -2 and -1, with PBPC reinfusion on day 0. On recovery, patients received CTCb on days -7 to -3, with PBPC reinfusion on day 0. G-CSF was administered after each cycle until WBCC recovery. For paclitaxel, an ANC >0.5 x 10(9)/L occurred at a median of 6 days (range 0-7 days) after PBPC reinfusion. The median nadir platelet count was 63 x 10(9)/L (range 6 x 10(9)/L-176 x 10(9)/L). Eight patients (12%) had platelet nadir <20 x 10(9)/L, and all recovered their counts to >20 x 10(9)/L on day 7. There was no clinical difference in days to engraftment between women receiving <2 or > or =2 x 10(6) CD34+ PBPC/kg following paclitaxel. All patients recovered neutrophil and platelet counts within 7 days after reinfusion of > or =1 x 10(6) CD34+ cells/kg and G-CSF. The data suggest that a paclitaxel dose of 825 mg/m2 is not myeloablative. For melphalan, median days to ANC >0.5 x 10(9)/L was 10 days (range 9-15), and platelet recovery to >20 x 10(9)/L was 13 days (range 0-28) after PBPC reinfusion. Median time to engraftment was more rapid in patients receiving > or =2 x 10(6) CD34+/kg versus <2 x 10(6)CD34+/kg, for both neutrophils (11 days versus 10 days, p = 0.05) and platelets (14 days versus 12 days, p < 0.01). Ninety-eight percent of patients infused with > or =2 x 10(6) CD34+/kg engrafted within 21 days. Following CTCb in this sequential regimen, a dose of > or =2 x 10(6) CD34+ cells/kg provided for significantly more rapid neutrophil engraftment than <2 x 10(6) CD34+ cells/kg (9 days versus 10 days,p = 0.01), but a dose > or =3 X 10(6) CD34+ cells/kg is necessary for reliable, rapid, and sustained neutrophil and platelet engraftment by day 21.     

Comparison of progenitor cell collection on day 4 or day 5 after steady-state stimulation with G-CSF alone in breast cancer patients: influence on CD34+ cell yield, subpopulation, and breast cancer cell contamination

To determine the influence of apheresis timing on CD34+ cell yield, subpopulation, and breast cancer cell contamination, 48 women with breast cancer were stimulated from steady-state hematopoiesis in a prospective but nonrandomized study with 2 x 5 microg/kg G-CSF s.c. alone, and apheresis was started either on day 4 (n = 24) or day 5 (n = 24). Forty-eight women with breast cancer (stage II/III, n = 30; stage IV; n = 12; inflammatory, n = 6) and a median age of 44 years were well balanced between the two groups. In group I, aphersis was started on day 4 and additionally performed on day 5 after G-CSF stimulation, and in group II, apheresis was started on day 5. CD34+ cell count and CD34+ cell subpopulation were determined according to international criteria. Breast cancer cell contamination was detected by immunocytology. The median CD34+ cell harvest on day 4 was 3.3 x 10(6)/kg body weight (range 0.5-12.8) and 6 x 10(6)/kg BW (range 0.3-30) for patients starting on day 5 (p = 0.01). Those patients starting on day 4 achieved a median CD34+ cell count of 4 x 10(6)/kg (range 0.7-13) on day 5 (NS). Twenty-one percent of group I and 71% of group II achieved >5 x 10(6)/kg BW CD34+ cells in the first apheresis, whereas <2.5 x 10(6)/kg BW CD34+ cells in the first apheresis were observed in 38% of group I and 16% of group II. No differences were observed between the CD34+ cell subpopulations, CD34+/CD38+ (10.5% versus 10.5%) and CD34+/Thyl+ (1.5% versus 1.8%). The CD34+ cell harvest from consecutive collecting on days 4 and 5 was nearly identical to the harvest starting on day 5 (6.4 versus 6 x 10(6)/kg). Collecting CD34+ progenitor cells after stimulation with G-CSF alone on day 5 results in a significantly higher cell yield than starting collecting on day 4. No differences in respect to breast cancer cell contamination and CD34+ cell subpopulation were observed.     

Filgrastim therapy in acute nonlymphoblastic leukemia

AIM: To specify effects of the granulocytic colony-stimulating factor (G-CSF) in the treatment of acute nonlymphoblastic leukemia. MATERIAL AND METHODS: Thirteen patients with acute myeloid leukemia (AML) were treated in the Hematological Clinic of the Higher Medical Institute in Plovdiv in 1996-1998. All of them received a standard induction therapy with cytosin arabinoside + daunorubicin (7 + 3 days). During the first neutropenic phase (neutrophils < 0.5 x 10(9)/l) G-CSF filgrastim was applied (5 microg/kg/day, s.c.) until a recovery of the neutrophil count reached > 1.0 x 10(9)/l and was maintained for 3 successive days. The control group consisting of patients matched by age, gender, an AML cytomorphologic variant was given the same therapy but filgrastim. RESULTS: The study group showed quicker recovery of the neutrophil count (12.6 vs 16.8 days), reduced febrile period (9.8 vs 12.4 days) and shorter duration of parenteral antibiotic treatment (9.8 vs 12.4 days) compared to controls. No statistically significant difference between both groups was found in the duration of the antimycotic treatment (p > 0.05). No cytological signs of aggravation of basic disease were absent in patients who received filgrastim. CONCLUSION: Administration of G-CSF in AML is useful as it promotes rapid overcoming of neutropenia and its complications.     

化疗加G-CSF和GM-CSF联合动员自体外周血干细胞

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

Changes in immunological and virological parameters in HIV-1 infected subjects following leukapheresis

In order to assess immune responses during HIV-1 therapeutic immunization, a large number of blood mononuclear cells (PBMC) are needed. Clinical tolerance and safety, as well as changes in immunological and virological parameters, were assessed, following leukapheresis in HIV-1 infected subjects with CD4(+) cell count >200 x 10(6)/l. PBMC were collected using a Fenwal CS3000 cell separator in 29 subjects with mean CD4(+) cell counts of 503 x 10(6)/l (range 172-1,119) and viral load of 2.5 log(10) copies/ml (range <1.7-5.4). Twenty-four (83%) subjects were on antiretroviral therapy while 5 (17%) were untreated. The blood volume processed was 7 L over a period of 3 hours. A mean value (+/- standard error) of 82 +/- 26 x 10(9)/l lymphocytes was collected by a single apheresis in a mean volume of 200 +/- 1.8 ml, containing 9.0 +/- 1.3 x 10(9)/l CD4(+) and 10.2 +/- 1.3 x 10(9)/l CD8(+) cells. The leukapheresis procedures were well tolerated and no immediate or delayed side effects were observed within 90 days of follow-up. No changes from blood pre-leukapheresis values were detected for white blood cells, lymphocytes, monocytes, CD8(+), CD34(+), naive and memory CD4(+) cell counts immediately after, 1 h, 7 days, or within 90 days after leukapheresis. However, absolute CD4(+) cell counts and percentage significantly increased from pre-leukapheresis values after 1 h (530 +/- 43 vs. 700 +/- 75 cell x 10(6)/l; 32.6 +/- 1.6 vs. 36.9 +/- 1.9%; P < 0.001 for both paired t-tests) before returning to pre-leukapheresis levels on day 7. No significant changes in viral load from pre-leukapheresis levels in treated or untreated subjects were detected at any time points. We conclude that leukapheresis in HIV-1 infected subjects with CD4(+) cell counts >200 x 10(6)/l is safe and induces a transient increase in the absolute and percentage of CD4(+) cell count without enhancing viral replication.     

Stem cell mobilization by G-CSF in solid and hematological malignancies: single daily dose is better than split dose in obese patients

In the past, variable results were reported for single daily and two divided daily doses of granulocyte colony-stimulating factor (G-CSF) in stem cell collection where no study exists investigating the effect of body mass index (BMI) on mobilization. The numbers of CD34(+) cells collected were compared in 86 patients with solid or hematological malignancies receiving either single daily (14 mug/kg/day) G-CSF (filgrastim) as group I (n=36) or two divided doses of G-CSF daily (2 x 7 mug/kg/day) as group II (n = 50). Both groups were divided into subgroups according to their BMI as group a (BMI 25 kg/m(2)). Two groups were similar in terms of BMI, gender, and disease characteristics. All patients have received G-CSF as a single or two divided doses subcutaneously and aphereses have been done on the 5th day. No significant difference in numbers of CD34(+) cells between groups Ia and Ib, groups IIa and IIb, and groups Ia and IIa was found. On the other hand, the mean ratio and the number of CD34(+) cells in group Ib were significantly higher than those of group IIb (0.58 +/- 0.06% vs. 0.37 +/- 0.26%, P = 0.01 and 3.67 +/- 0.65 x 10(4)/kg/ml vs. 1.92 +/- 0.37 x 10(4)/kg/ml, P= 0.02). In conclusion, in patients with BMI >25 kg/m(2), once daily G-CSF compared to split dose administration induces a greater number of CD34(+) stem cell mobilization, which suggests the presence of a different pharmacokinetics in obese patients.     

Factors influencing mobilization and engraftment in patients with metastatic breast cancer undergoing PBSC transplantation.

Factors influencing mobilization and engraftment of PBSC were analyzed in 38 patients with metastatic breast cancer who were undergoing PBSC transplantation. None of these patients had had previous chemotherapy for metastatic disease. PBSC were mobilized with cyclophosphamide (CY) and G-CSF (n = 21) or CY and etoposide (CY-etoposide) and G-CSF (n = 17). All received cyclophosphamide 6000 mg/m2, thiotepa 500 mg/m2, and carboplatin 800 mg/m2 (CTCb) as preparative regimen. PBSC infusion was followed by G-CSF at 5 microg/kg in 30 patients or 10 microg/kg in 8 patients. A median number of 27 x 10(6) CD34+ cells/kg was obtained with a median of four aphereses. Previous chemotherapy, radiation therapy, marrow disease, time from previous chemotherapy to mobilization, and type of mobilization regimen did not have a statistically significant effect on collection efficiency (CE). CE was defined as the total number of CD34+ collected/number of collections. Engraftment was rapid, with patients reaching a neutrophil count of 0.5 x 10(9)/L a median of 9 days (range 7-23) and a platelet count of 20 x 10(9)/L a median of 12 days (range 8-28) after transplantation. Shorter times to platelet recovery were associated with a higher number of CD34+ cells infused (p = 0.012), CY mobilization (p = 0.033), and a lower number of prior chemotherapy cycles (p = 0.022). When the number of CD34+ cells was included in the proportional hazard model, no other variables were found to be significant predictors of platelet engraftment. Time to neutrophil recovery was negatively associated with the dose of G-CSF used after transplantation (p = 0.036) CD34 cell dose is an important predictor of engraftment kinetics. A posttransplant dose of G-CSF improves neutrophil recovery. For patients with metastatic breast cancer and no previous chemotherapy for metastatic disease, we have no evidence for a difference between CY and CY-Etoposide as the mobilization regimen.     

CD34+ cell enrichment for autologous peripheral blood stem cell transplantation by use of the CliniMACs device

Several devices for selection of CD34+ peripheral blood stem cells (PBSC) have been used during the last years for reducing tumor cell contamination of the graft. The new CliniMACS system (magnetic-activated cell separation system by Miltenyi Biotech GmbH, Bergisch-Gladbach, Germany) was recently approved for clinical use in Europe. To evaluate its purging efficiency and engraftment data in the autologous transplant, PBSC from 28 adult patients with various malignant diseases (non-Hodgkin's lymphoma, n = 17; chronic lymphocytic leukemia, n = 5; multiple myeloma, n = 4; acute lymphocytic leukemia, n = 1; medulloblastoma, n = 1) were mobilized by chemotherapy and granulocyte colony-stimulating factor (G-CSF) (10 microg/kg per day). Thirty leukapheresis products from 28 patients with a median of 4.4 x 10(8) nucleated cells/kg body weight (bw)(range 0.6-10.8 x 10(8)/kg bw) and a median of 7.1 x 10(6) CD34+ cells/kg bw (range 2.8 to 18.8 x 10(6)/kg bw) were selected using the Cobe spectra cell separator (Cobe BCT Inc., Lakewood, CO). After the CliniMACS procedure, the median yield of CD34+ selected cells was 4.5 x 10(6)/kg (range 2.2-11.1 X 10(6)/kg bw) with a median recovery of 69.5% (range 46.9-87.3%) and a median purity of 97.7% (range 89.4-99.8%). The procedure did not alter viability of selected cells, which was tested by propidium iodide staining. So far, purified PBSC were used for autologous transplantation in 15 out of 28 patients after total body irradiation and/or high-dose chemotherapy. Median time to reach an absolute neutrophil count > 500/microl was 12 days (range 10-18 days), platelet recovery >50,000/microl occurred at day + 16 (range 11-22). With a median follow-up time of 12 months (range 3-19), 5 patients died of relapse. We confirmed the feasibility and safety of the CliniMACS CD34+ cell enrichment procedure in adult patients with autologous PBSC transplantation.     

The effect of G-CSF on lymphocyte subsets and CD34+ cells in allogeneic stem cell transplantation.

The effect of granulocyte colony-stimulating factor (G-CSF) on peripheral blood lymphocytes (PBL) and CD34+ cell frequency in the apheresis product has been determined in 25 healthy stem cell donors. Peripheral blood mononuclear cells (PBMNC) were collected after five days of G-CSF 10 microg/kg/day s.c., which was well tolerated. The median number of leukocytes increased eight-fold over that of pretreatment levels. Collection of PBMNC lasted a median of two (range, 1-3) days. The mean mononuclear cell (MNC) count and total lymphocyte percentage were 6.69 x 10(8)/kg and 59.08%, respectively, and the frequency of CD34+ cell expression was 2.1% in the apheresis product. The frequency of CD3+, CD4+, CD25+, NK and CD122+ cell expressions in mobilized PBMNC and PBL showed no significant difference. However, the frequency of CD8+, CD8+28+, CD3+DR+, CD19+, CD20+ and CD22+ B cells expression in the apheresis product increased significantly compared to steady-state PBL. In contrast, the frequency of the CD11 a+ and CD8+38+ cell expressions in the apheresis product was decreased compared to the steady-state PBL. The mean yield of CD34+ and CD3+ cells were 13.6 x 10(6) and 2.69 x 10(8)/kg of recipient body weight (RBW), respectively. Following allograft all patients engrafted with >0.5 x 10(9)/l neutrophil and < or = 20 x 10(9)/l platelets on a median of day 13 and 12, respectively. Nine patients had grade II-IV acute GVHD and chronic GVHD occurred in eight patients. Four patients died due to transplant-related complications. There was one late engraftment failure which occurred on the fifth month. Thirteen patients are still alive. In conclusion, these results indicate that administration of G-CSF at 10 microg/kg/day in normal donors alters the lymphocyte subsets and there are significant differences in the lymphocyte contents of the recipients before apheresis and in apheresis product.     

Factors influencing collection and engraftment of CD34+ cells in patients with breast cancer following high-dose chemotherapy and autologous peripheral blood progenitor cell transplantation

Although autologous PBPC transplantation is being used increasingly for the treatment of breast cancer, there are few data on factors influencing mobilization and engraftment in these patients. We have analyzed these factors in 70 patients with advanced or metastatic breast cancer undergoing autologous PBPC transplantation. All patients were mobilized after stimulation with G-CSF, and a median of 3.16 x 10(6)/kg CD34+ cells (range 0.75-23.33) were infused. All patients received conditioning with a combination of cyclophosphamide, thiotepa, and carboplatin, and postinfusion G-CSF was administered to 60 patients. The median times to reach 0.5 x 10(9)/L and 1 x 10(9)/L neutrophils were 10 and 11 days, respectively. The median times to obtain 20 x 10(9)/L and 50 x 10(9)/L platelets were 12 and 18 days, respectively. An analysis of factors that influence CD34+ cell collection was performed by linear regression. Previous radiation therapy and increasing age were associated with lower numbers of CD34+ cells collected. Those variables that could influence the tempo of engraftment were examined by multivariate analysis using Cox regression models. The number of CD34+ cells infused was found to influence both neutrophil and platelet recovery. The use of G-CSF after transplant, accelerated neutrophil recovery, and having more than six cycles of previous chemotherapy was an unfavorable factor for recovering >50 x 10(9)/L platelets.     

大剂量足叶乙甙和G-CSF用于恶性血液病外周血造血干/祖细胞动员

为了观察大剂量足叶乙甙(VP16)和粒细胞集落刺激因子(G-CSF)在恶性血液病人动员采集自体外周血造血干/祖细胞的有效性和安全性,对10例恶性血液病患者(多发性骨髓瘤6例,非霍奇金淋巴瘤4例),第1天用足叶乙甙1.6g/m2静脉持续滴注10小时,第3天起给予G-CSF5μg/kg,每日1次,皮下注射,直至采集结束。结果显示:用VP16后平均第11(9-13)天开始外周血造血干/祖细胞单采,获CD34+细胞9.4×106/kg(4.2-17.3×106/kg),每例CD34+细胞>4.0×106/kg。平均采集次数2.6(1-4)次。1例发生口咽黏膜炎、2例尿道炎、咽喉炎。结论:足叶乙甙1.6g/m2和G-CSF5μg/kg是恶性血液病动员采集自体干祖细胞的有效安全方案。     

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

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

外科危重病患者外周血淋巴细胞凋亡与预后的关系

目的探讨淋巴细胞凋亡在外科危重病患者中的作用机制及其与预后的关系。方法采用流式细胞仪分别测定外科大手术后危重病患者(39例)和正常对照组(30例)外周血淋巴细胞凋亡;采用血细胞分析仪测定淋巴细胞计数,并分析其与继发感染及重症加强治疗病房(ICU)住院时间的关系。结果外科危重病患者淋巴细胞凋亡率高于正常对照组(10.82±3.32)%比(2.89±1.17)%,P<0.01,淋巴细胞计数则显著降低(1.41±1.26)×109/L比(2.58±0.62)×109/L,P<0.01。与无感染组比较,继发感染组淋巴细胞凋亡率明显增强(12.67±3.11)%比(9.24±2.63)%,P<0.01;入ICU后1d是否继发感染的两组患者淋巴细胞计数间差异无显著性,但3d和5d时继发感染组淋巴细胞计数则明显低于无感染组分别为(0.68±0.35)×109/L和(0.72±0.40)×109/L)比(1.30±1.33)×109/L和(1.34±1.11)×109/L,差异均有显著性(P均<0.05)。外科术后危重病患者的ICU住院时间与淋巴细胞凋亡率呈正相关(r=0.412,P=0.009),与1、3和5d淋巴细胞计数呈负相关,与1d和5d差异均有显著性(r1=-0.333,P1=0.039;r3=-0.308,P3=0.057;r5=-0.361,P5=0.024)。结论外科危重病患者外周血淋巴细胞凋亡率增强、淋巴细胞计数下降,且与继发感染及ICU住院时间延长相关;有效调控淋巴细胞凋亡可能有助于改善外科术后危重病患者的预后。     

Granulocyte transfusions from G-CSF-stimulated donors for the treatment of severe infections in neutropenic pediatric patients with onco-hematological diseases

From March 1994 to January 2001, 15 courses of granulocyte transfusion (GTX) were administered to 13 neutropenic patients (6 male and 7 female patients; median age 7 years, range 3 months to 14 years) affected by: acute lymphoblastic leukemia (ALL) in 6 cases, acute myeloid leukemia (AML) in 5, very severe aplastic anemia in 1, and familial erythrophagocytic lymphohistiocytosis (FEL) in 1. Infections were classified as microbiologically defined and clinically defined infections in 8 and 7 episodes, respectively. Before the GTX transfusions, broad-spectrum antibacterial and antifungal therapy had been administered for a median of 12 (range 5-28) and 8 days (range 2-50), respectively, with no improvement. G-CSF was administered prior to GTX in 9 episodes of infection, with a median of 9 days of treatment (range 4-30). Leukapheresis was obtained from 15 related donors (father, 10; mother, 3; sister, 1; aunt, 1) after s.c. stimulation with G-CSF, 300 micro g daily, starting from day -3 (where day 0 was the day of the first granulocyte collection) and continuing throughout the period of GTX treatment. The donors' median white blood cell (WBC) count at leukapheresis was 31.6 x 10(9)/l (range 12-56), and the median yield was 31.39 x 10(9) WBC (range 2.96-64.73 x 10(9)), with a proportion of PMN of 90-95%. Overall, 70 GTX were administered, with a median of 4 GTX per episode of infection (range 2-11). The combination of GTX with antimicrobial therapy led to complete or partial recovery in 6 and in 3 of 15 episodes (60%), respectively. Priming of the donor with G-CSF was well tolerated, the most common side-effects being bone pain, malaise and paresthesia. All donors are alive and well after a median of 4.5 years (range 0.8-7.7) from donation. We conclude that GTX is potentially useful when the severity of the infection and the host's immunodeficiency make any other antimicrobial treatment ineffectual. Long-term safety data on the stimulation of donors with G-CSF have been reassuring to date. Further controlled studies are needed to assess the exact role of GTX in the outcome of neutropenic patients with severe infection and any criteria for patient selection and the timing of GTX administration.     

Treatment with granulocyte colony-stimulating factor increases interleukin-1 receptor antagonist levels during engraftment following allogeneic stem-cell transplantation

BACKGROUND: The effect of treatment with granulocyte colony-stimulating factor (G-CSF) on interleukin-1 receptor antagonist (IL-1ra) plasma concentrations as well as the role of IL-1ra on leucocyte recovery and parameters of infection within the first 30 days after haematopietic stem-cell transplantation (HSCT) are not well known. MATERIAL AND METHODS: Twenty-seven patients undergoing myeloablative therapy followed by allogeneic SCT for various haematological disorders were either treated with (n = 18) or without (n = 9) G-CSF. IL-1ra plasma levels were serially determined by ELISA starting at day - 1 and continued until patients were engrafted. RESULTS: Patients receiving G-CSF had significantly shorter neutropenic periods and significantly lower mean C-reactive protein serum levels during the first 3 weeks succeeding bone marrow transplantation (BMT). Importantly, starting at day + 11 and paralleling the rise of peripheral blood leucocytes, increasing IL-1ra plasma concentrations were observed in both treatment groups. However, the magnitude of the IL-1ra surge was far greater in the G-CSF treatment group. Peak IL-1ra plasma level observed on day + 19 was 882.3 +/- 879.2 pg mL(-1) (mean +/- SD) in patients receiving G-CSF compared with 285.8 +/- 175.2 pg mL(-1) (mean +/- SD) in patients not receiving G-CSF (P = 0.0130). Furthermore, a direct correlation of IL-1ra with peripheral blood leucocytes was verified by the Spearman rank test (P = 0.0025). CONCLUSION: Granulocyte colony-stimulating factor-mediated acceleration of neutrophil recovery following myeloablative therapy correlated with increased IL-1ra plasma concentrations. Our data suggest that IL-1ra constitutes an intrinsic component of the anti-inflammatory and neutrophil differentiating efficacy of G-CSF and, thus, IL-1ra may be required for the in vivo activity of G-CSF.     

Mobilization of peripheral blood stem cells in high-risk breast cancer patients using G-CSF after standard dose docetaxel

Chemotherapy, in addition to recombinant growth factors, has been effective in mobilizing stem cells. Unfortunately, the use of chemotherapy for this purpose has resulted in profound myelosuppression and increased morbidity. Docetaxel, the single most active agent in the treatment of advanced breast cancer, was evaluated for its potential to mobilize stem cells when given at conventional doses followed by granulocyte colony-stimulating factor (G-CSF). Sixteen high-risk breast cancer patients were mobilized with a regimen consisting of docetaxel (100 mg/m2) followed by daily G-CSF (10 microg/kg), beginning 72 h after the docetaxel, and continuing until completion of the apheresis. The median white blood cell count (WBC) nadir was 1,000/microl (range 500 to 4000/microl ) occurring a median of 6 days (range 4 to 9 days) after the docetaxel. No patient experienced a neutropenic febrile episode due to the mobilization regimen. The median time interval for initiating the apheresis was 8 days (range 6 to 11 days) following the docetaxel. The median number of apheresis was 2 (range 1 to 3) in each patient. Stem cell recovery as measured by the CD34 cell count x 10(6)/kg was a median of 5.2 (range 1.4 to 15.1). A significant correlation was found between CFU-GM, BFU-E, and CFU-GEMM/kg and CD34 cells/kg (r = 0.891, 0.945, and 0.749, respectively, p < 0.001). When our results were compared to a matched cohort receiving G-CSF alone, the docetaxel group demonstrated a superior CD34 cells/kg yield (p = <0.001). Following myeloablative chemotherapy consisting of thiotepa and cyclophosphamide with or without carboplatinum, the hematopoetic recovery determined by an absolute neutrophil count (ANC) of greater than 500/microl and an unsupported platelet count of > or =20,000/microl for 48 h, was a median of 10 days (range 9 to 14 days) and 10 days (range 8 to 30 days), respectively. The results demonstrate that conventional dose docetaxel, combined with G-CSF, is an effective mobilization regimen with minimal toxicity in high-risk breast cancer patients.     

双次自体外周血干细胞移植治疗多发性骨髓瘤

为了探讨双次自体外周血干细胞移植治疗多发性骨髓瘤（MM）的安全性及疗效,为1例49岁女性MM患者行双次自体外周血干细胞移植。第1次移植的动员方案：环磷酰胺2g/m2×1天,粒细胞集落刺激因子（G-CSF）[（10μg/（kg.d）]×5天。预处理方案：马法兰（melphalan）200mg/m^2。自体外周血干细胞回输：单个核细胞（MNC）6.1×10^8/kg;CD34＋细胞4.7×10^6/kg。6个月后行第2次移植的动员方案：G-CSF[（10μg/（kg.d）]×5天。预处理方案：马法兰200mg/m^2。自体外周血干细胞回输：MNC10.2×10^8/kg;CD34＋细胞5.9×106/kg。结果表明：第1次移植后17天中性粒细胞绝对值（ANC）回升至0.5×10^9/L,15天血小板回升至20×10^9/L;第2次移植后22天ANC回升至0.5×10^9/L,13天血小板回升至20×10^9/L。双次移植过程中均未出现明显毒副反应,无严重并发症。经上述治疗后患者的骨痛、贫血症状消失,第2次移植后随访7个月,患者情况良好,仍处于完全缓解（CR）状态。结论：双次自体外周血干细胞移植治疗多发性骨髓瘤是安全、有效和可行的。     

序贯两次自体外周血造血干细胞移植治疗初治多发性骨髓瘤

为了初步评价序贯自体造血干细胞移植（T-APBSCT）治疗MM的疗效,对3例初治多发性骨髓瘤（MM）患者经正规化疗后进行序贯两次T-APBSCT,初次移植：动员方案为环磷酰胺（CTX）联合G-CSF5μg/（kg.d）,预处理方案为大剂量马法兰;第二次移植：动员方案为CTX＋足叶乙甙联合G-CSF,预处理方案为大剂量马法兰±全身照射。3例序贯两次移植的间隔分别为31、15和27周。两次移植回输的单个核细胞数分别为4.7×10^8/kg、2.798×10^8/kg、6.08×10^8/kg和1.67×10^8/kg、2.798×10^8/kg、4.28×10^8/kg;CD34^＋细胞分别为3.25×10^6/kg、9.6×10^6/kg、5.91×10^6/kg和6.9×10^6/kg、9.6×10^6/kg、5.91×10^6/kg。结果表明：所有患者的造血均快速重建,每两次移植后中性粒细胞数≥1×10^9/L的时间为12、0、10天和12、25、0天,血小板数≥20×10^9/L的时间分别为12、0、10天和11、25、20天。随访时间44（19-58）月,2例存活（1例完全缓解,1例于处于平台期）,1例于T-APB-SCT后58月死亡。结论：两次序贯自体外周血干细胞移植是治疗多发性骨髓的有效手段,动员方法简便安全,患者对预处理方案耐受性好,值得临床进一步研究探索。     

Time course changes in the count of peripheral granulocytes in children with acquired aplastic anemias treated with antithymocyte globulin,cyclosporin A and granulocytic colony stimulating factor

AIM: To examine the pattern of changes in the count of peripheral granulocytes in children with aplastic anemias (AA), receiving a combined immunosuppressive therapy with antithymocytic globulin (ATG) and cyclosporin A in combination with granulocytic colony-stimulating factor (G-CSF). MATERIALS AND METHODS: 31 children (17 boys and 14 girls) aged 2-15 years (median 9 years) with newly diagnosed severe and very severe acquired AA took a combined immunosuppressive therapy with ATG and cyclosporin A in combination with G-CSF in an initial dose of 10 micrograms/kg a day. RESULTS: A three-linear and response was recorded in 19 (61%) children, an isolated granulocytic response was in 26 (84%). The interval median before the recovery of granulocytes to 1.5 x 10(9)/l and 5 x 10(9)/l was 19 and 38 days, respectively. CONCLUSION: Use of G-CSF may increase the count of granulocytes in the vast majority of patients with AA, without dramatic influence on the frequency of a three-linear response. Intermittent use of G-CSF may maintain the count of granulocytes long at the safe level and reduce the cost of treatment.