Prospective,concurrent comparison of the Cobe Spectra and Haemonetics MCS-3P cell separators for leukapheresis after high-dose filgrastim in patients with hematologic malignancies

A prospective study was undertaken to compare the mononuclear cell, CD34+ cell, and CFU-GM yields of the Haemonetics MCS-3P and the Cobe Spectra cell separators in ten patients (nine multiple myeloma and one non-Hodgkin lymphoma) on two consecutive days after mobilization with high-dose filgrastim (12–16 μg/k) for 4 days. All patients were harvested once on each machine, five starting on each machine. The target duration of the procedure on the Spectra was 160 minutes, and the target blood volume processed on the MCS-3P was 60–70 ml/kg body weight. Both machines were operating on the 1995 software versions supplied by the respective manufacturers. The time taken for the procedure was significantly longer with the Haemonetics machine. The volumes of blood processed and the product collected were significantly higher with the Spectra, as were the absolute mononuclear and CD34+ cell yields, and yields per unit time. Mononuclear and CD34+ cell yields per unit volume of blood processed were comparable for both machines. The differences in CFU-GM yields were not significant, largely because of wide interpatient variations. The extent of platelet depletion as a result of the procedure was greater with the Spectra because of the higher blood volume being processed. We conclude that the Cobe Spectra is a significantly faster machine than the Haemonetics MCS-3P; and consequently, its use is associated with higher mononuclear and CD34+ cell yields. J. Clin. Apheresis 12:63–67, 1997. © 1997 Wiley-Liss, Inc.     

Stimulation of Kaposi's sarcoma-associated herpesvirus viremia during hematopoietic stem cell mobilization with filgrastim

The effects of hematopoietic stem cell (HSC) mobilization on Kaposi's sarcoma-associated herpesvirus (KSHV) were evaluated in three KSHV and human immunodeficiency virus type 1 co-infected subjects. KSHV DNA was not detected in purified CD34+ cell preparations from the period of filgrastim treatment. However, two of 3 subjects had transiently increased cell-free plasma KSHV DNA during filgrastim treatment. Peak plasma KSHV DNA (2,600 and 4,300 copies/mL) occurred on day 4 and declined to below the limit of detection by day 7. These findings suggest that, although CD34+ cell preparations do not have evidence of KSHV infection, HSC mobilization may stimulate KSHV replication in other cellular compartments that contribute to KSHV viremia.     

A phase I/II study of 4 monthly courses of high-dose cyclophosphamide and thiotepa for metastatic breast cancer patients

This pilot phase I/II study intended to determine the maximum tolerated dose of cyclophosphamide and thiotepa administered on four consecutive courses with peripheral blood progenitor cell and granulocyte-colony stimulating factor support, as first-line therapy for hormone-refractory metastatic breast cancer patients. Twenty-eight patients were entered in the study. After two courses of epirubicin (120 mg m(-2)) and cyclophosphamide (2 g m(-2)) followed by granulocyte-colony stimulating factor injection and leukaphereses, patients received four cycles of cyclophosphamide and thiotepa. Each cycle was followed by peripheral blood progenitor cell and granulocyte-colony stimulating factor supports, then repeated every 28 to 35 days. Six escalating dose levels of cyclophosphamide and thiotepa were planned, beginning at cyclophosphamide 1.5 g m(-2) and thiotepa 200 mg m(-2). At least three patients were enrolled for each dose level. Eighteen patients completed the study. The maximum tolerated dose was 3000 mg m(-2) cyclophosphamide and 400 mg m(-2) thiotepa per course. Haematological toxicity was manageable on an outpatient basis and did not increase significantly with dose escalation. Dose-limiting toxicity was chemotherapy-induced immunosuppression, which resulted in one toxic death and two life-threatening infections. Median times to treatment failure and survival were 11 and 26 months, respectively. Three patients were alive, free of disease 30 months after completion of the study. Such therapy allows for high-dose intensity and high cumulative doses on a short period of time with manageable toxicity.     

Bronchiolitis obliterans organizing pneumonia in a patient with non-Hodgkin's lymphoma following R-CHOP and pegylated filgrastim

Bronchiolitis obliterans organizing pneumonia (BOOP) presents with fever, dyspnoea, pleuritic chest pain and hypoxia. The diagnosis can be made from radiological appearances on chest radiograph and CT scan correlated with histological findings following biopsy. We present a 52-year-old gentleman undergoing treatment for high grade non-Hodgkin's lymphoma who developed respiratory symptoms during chemotherapy. BOOP was diagnosed and he responded well to oral prednisolone. The cause of BOOP is often not certain. However, in this case we suspect pegylated filgrastim or rituximab as possible agents.     

Efficacy and safety of two different rG-CSF preparations in the treatment of patients with severe congenital neutropenia

In patients with severe congenital neutropenia (SCN), the absolute neutrophil count (ANC) is raised during treatment with granulocyte colony-stimulating factor (G-CSF), resulting in a marked reduction of bacterial infection. Some patients, however, still have recurrent but less severe bacterial infections and severe periodontal infections. As it has been suggested that the biological activity of glycosylated recombinant human G-CSF (rHuG-CSF, i.e. lenograstim) is higher than the non-glycosylated form (i.e. filgrastim), we compared the two given in equimolar doses. Seven SCN patients participated in an open, randomized, double crossover study comprising 60 weeks, with four 12-week periods when the two drugs alternated after a 12-week run-in-period. The mean ANC values, sampled every second week, were 5.1 x 10(9)/l during filgrastim treatment and 4.2 x 10(9)/l during lenograstim treatment (P = 0.042). The ANC levels were also significantly higher during filgrastim treatment, when comparing each complementary pair of ANC measurements (P = 0.011) as well as the mean ANC values during each 12-week treatment period (P = 0.033). There were no differences regarding the frequency of infection, antibiotic treatment, gingival bleeding and the number of hospital admissions between the groups. We conclude that filgrastim and lenograstim displayed equal clinical efficacy, but that ANC levels were higher during filgrastim treatment, when administered in equimolar doses.     

聚乙二醇化重组人粒细胞刺激因子与重组人粒细胞刺激因子临床疗效比较

目的：比较乳腺癌TAC方案化疗后,应用聚乙二醇化重组人粒细胞刺激因子和人粒细胞刺激因子预防粒细胞减少的临床疗效。方法：选取2013年1-8月入院接受TAC方案化疗的乳腺癌患者共60例。30例为试验组,化疗结束后48 h给予聚乙二醇化重组人粒细胞刺激因子（PEG-rhG-CSF）;30例为对照组,化疗结束后48 h给予重组人粒细胞刺激因子（rhG-CSF）。结果：试验组化疗间歇期中性粒细胞减少、感染病例明显少于对照组,差异有统计学意义（P＆lt;0.05）。结论：乳腺癌TAC方案化疗后应用聚乙二醇化重组人粒细胞刺激因子预防中性粒细胞减少疗效确切,值得临床推广应用。     

Angiotensin 1 – 7 stimulation of platelet recovery

Introduction: Thrombocytopenia is an abnormally low number of platelets in the blood resulting from either too few platelets being produced or existing platelets being destroyed. Severe thrombocytopenia leads to excessive bleeding and can be the result of numerous medical conditions or a side effect of medications or treatments. Although platelet transfusions are typically administered to correct thrombocytopenia, transfusions represent a temporary and unsustainable solution. As there is a limited supply of platelet units available for transfusion, along with the significant financial cost and risk of infection, investigation to uncover mechanisms that boost platelet production may have important clinical and therapeutic implications. Treatment with angiotensin 1 – 7 (A(1 – 7)) has been shown in a preclinical and clinical evaluations to have a positive effect on platelet recovery.

Areas covered: The authors provide an overview of the current treatment options available for platelet recovery and highlight the need for alternatives. Following on, the authors discuss the use of A(1 – 7) as a potential therapeutic option for platelet recovery, including its safety and efficacy.

Expert opinion: Current evidence provides a good basis for continued research and evaluation of the benefits of A(1 – 7) treatment in stimulating platelet recovery following myelosuppression. A(1 – 7) therapy has the potential to make a significant contribution to healthcare by providing standalone and additive treatments to address unmet medical needs and life-threatening diseases by utilizing the regenerative arm of the renin–angiotensin system.     

肿瘤化疗后中性粒细胞缺乏症20例临床分析

目的:探讨恶性肿瘤患者化疗后中性粒细胞缺乏症的治疗方法. 方法: 20例中性粒细胞缺乏症患者,一经确诊,立即入住单人病房,严格消毒隔离.使用重组人粒细胞集落刺激因子针(G-CSF )150μg-300μg皮下注射qd连用3-7天升白细胞治疗.19例患者均使用抗生素防治感染,其中14例使用第2、3代头孢菌素+左氧氟沙星治疗. 2例使用美罗培南注射剂治疗.结果: 20例患者中18例白细胞、中性粒细胞均回升至正常,白细胞回升至正常的时间为3-7日.发热患者经治疗后1-8日体温降至正常,外周血白细胞呈上升之势.结论: 使用重组人粒细胞集落刺激因子(G-CSF )皮下注射,辅以第2、3代头孢菌素+左氧氟沙星,及提高机体免疫力等,可有效治疗中性粒细胞缺乏症.     

Efficacious and save use of biosimilar filgrastim for hematopoietic progenitor cell chemo‐mobilization with vinorelbine in multiple myeloma patients

Biosimilars are increasingly being licensed as equipotent drugs, although efficacy and safety data are not available for all clinical indications. Accordingly, the efficacy of the biosimilar filgrastim Zarzio® combined with vinorelbine for chemo‐mobilization of CD34+ hematopoietic progenitor cells (HPC) in patients with multiple myeloma has not been evaluated yet. We compared the efficacy of vinorelbine combined with this biosimilar filgrastim for HPC mobilization to vinorelbine plus original filgrastim (Neupogen®). Overall, 105 multiple myeloma patients received vinorelbine 35 mg/m² intravenously on day 1 and either original filgrastim (n = 61;58%) or biosimilar filgrastim (n = 44;42%) at a dose of 5 µg per kg body weight (BW) twice daily subcutaneously starting day 4 until the end of the collection procedure. Leukapheresis was scheduled to start on day 8 and performed for a maximum of three consecutive days until at least 4 × 10⁶ HPC/kg BW were collected. All patients proceeded to leukapheresis. In 102 (97%) patients the leukapheresis sessions were started as planned at day 8. The median number of collected HPC was 7.3 × 10⁶/kg BW (0.2–18.3) with original filgrastim compared to 9 × 10⁶/kg BW (4.2‐23.8) with the biosimilar filgrastim (P = 0.16). HPC collection was successful in 57 (93%) of 61 patients of the original group and in all 44 (100%) patients of the biosimilar group (P = 0.14). No differences were observed regarding side effects. Duration of neutrophil engraftment after autologous HPC transplantation was similar between the two groups (P = 0.17). Biosimilar and original filgrastim achieve comparable results in combination with vinorelbine regarding HPC mobilization and transplantation outcome in multiple myeloma patients. J. Clin. Apheresis 32:21–26, 2017. © 2016 Wiley Periodicals, Inc.