Combined administration of G-CSF and dexamethasone for the mobilization of granulocytes in normal donors: optimization of dosing

BACKGROUND: The clinical utility of neutrophil (polymorphonuclear leukocyte, PMN) transfusion therapy has been compromised, in part, by the inability to obtain sufficient quantities of functional neutrophils from donors. Mobilization of PMNs in the peripheral blood of normal volunteers has been shown to be superior when G-CSF is administered in conjunction with dexamethasone to that when either agent is administered alone. The current study was conducted to determine the optimal dosages of G-CSF and dexamethasone to be administered to donors in a granulocyte transfusion program. STUDY DESIGN AND METHODS: Five normal subjects were randomly assigned to each of the following single-dose regimens over five consecutive weeks: 1) subcutaneous (SC) G-CSF at 600 microg and oral (PO) dexamethasone at 8 mg; 2) SC G-CSF at 450 microg and PO dexamethasone at 8 mg; 3) SC G-CSF at 450 microg and PO dexamethasone at 12 mg; 4) SC G-CSF at 450 microg; and 5) PO dexamethasone at 12 mg. Venous blood was collected at 0, 6, 12, and 24 hours after drug administration for determination of absolute neutrophil count (ANC). Side effects of drug administration were recorded by using a standardized symptom questionnaire. RESULTS: Maximal ANC was achieved at 12 hours after administration of drugs under each regimen. All four regimens containing G-CSF caused greater than 10-fold increases in the ANC. When administered in conjunction with dexamethasone, G-CSF resulted in statistically similar PMN mobilization at dosages of 450 microg and 600 microg. The combined single-dose regimen of SC G-CSF at 450 microg and PO dexamethasone at 8 mg increased the mean ANC from a baseline value of 2800 per microL to 37,900 per microL at 12 hours after administration. This regimen was well tolerated by the normal volunteers. CONCLUSION: In a single-dose format designed for clinical granulocyte transfusion programs, optimal PMN mobilization can be achieved in normal donors with a combined regimen of SC G-CSF at 450 microg, and PO dexamethasone at 8 microg.     

Donor tolerance and results of stimulation with G-CSF alone or in combination with dexamethasone for the collection of granulocytes

Stimulation of healthy granulocyte donors allows the collection of therapeutic doses of granulocytes. The stimulation with G-CSF alone was compared with G-CSF plus dexamethasone. Blood samples were drawn at baseline, at leukapheresis, and at follow-up visit. Donors answered a questionnaire to evaluate side effects of the stimulation regimen. The combination of G-CSF and dexamethasone resulted in higher WBC count than G-CSF alone (39.4 +/- 7.8 vs. 34.8 +/- 8.3/nl). Glucose (136 +/- 45 mg/dl) and lactate dehydrogenase (195 +/- 38) increased significantly after stimulation with G-CSF plus dexamethasone but returned to baseline levels at the follow-up visit. Generally, stimulation was well tolerated by the donors. A higher rate of mild bone pain and headache was experienced in donors stimulated with G-CSF plus dexamethasone than in donors receiving G-CSF alone. Fatigue and myalgia were reported at similar rates in both groups. A high proportion of the donors stated that they would accept a further stimulation and granulocyte donation. At the follow-up visit, blood counts and chemistry had returned to normal values.     

A dose-response analysis of lenograstim plus dexamethasone for neutrophil mobilization and collection

BACKGROUND: The objective was to evaluate the dose-response relationship of lenograstim plus dexamethasone for neutrophil mobilization and collection. STUDY DESIGN AND METHODS: In a prospective study, 260 healthy volunteers received oral dexamethasone (8 mg) plus a single subcutaneous injection of glycosylated granulocyte-colony-stimulating factor (G-CSF; lenograstim) at medians of 1.5 (1.0-2.3) microg per kg (n = 43), 3 (2.4-4.1) microg per kg (n = 73), 6 (4.3-7.9) microg per kg (n = 123), and 12 (8.2-17.2) microg per kg (n = 21) and underwent neutrophil collections with a polymorphonucleated neutrophil (PMN) program. White blood cell (WBC) counts and PMN mobilization and collection results were compared, and the severity and clinical significance of donor adverse reactions were evaluated. Fifty-two neutropenic patients (29 children, 23 adults) underwent 271 neutrophil transfusions (GTXs) every other day to maintain WBC levels continuously above 0.5 x 10(9) per L. RESULTS: Within the dose range 1.5, 3, and 6 microg per kg, each doubling step was associated with a 10 to 15 percent PMN increase in peripheral blood up to 32.8 (19.1-49.2) x 10(9) per L (6 microg/kg; p 相似文献   

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   

Predictive value of circulating immature cell counts in peripheral blood for timing of peripheral blood progenitor cell collection after G-CSF plus chemotherapy-induced mobilization

BACKGROUND: Enumeration of CD34+ cells in peripheral blood (PB) before apheresis predicts the number of CD34+ cells collected, although flow cytometric techniques used are complex and expensive. In an attempt to determine the optimal timing for peripheral blood progenitor cell (PBPC) collection, the usefulness of circulating immature cell (CIC) counts in PB was evaluated. STUDY DESIGN AND METHODS: CIC counts in PB and CD34+ cell counts in the apheresis product from 249 collections were assessed, and the relationship between these two parameters was evaluated by with the Pearson rank correlation analysis, the Fisher exact test, and the U-test. RESULTS: CIC counts were correlated significantly with the number of CD34+ cells per kg of patient's body weight in the apheresis product (Pearson rank correlation analysis: r = 0.635, p < 0.0001). When a level of 1 x 10(9) CICs per L was selected as a cutoff value, the sensitivity and specificity for collecting more than 1 x 10(6) CD34+ cells per kg of body weight were 75.7 and 85.5 percent, respectively. CONCLUSION: The present study strongly suggests that the number of CICs in PB may estimate the number of CD34+ cells collected. The data indicate that CIC counts above 1 x 10(9) per L can be used as a good predictor for PBPC collections containing more than 1 x 10(6) CD34+ cells per kg of body weight in a single apheresis procedure.     

Evaluation and comparison of three mobilization methods for the collection of granulocytes

BACKGROUND: Cancer chemotherapeutic regimens have become more potent and myeloablative. As a consequence, morbidity and mortality due to opportunistic infections have become a major challenge. The provision of adequate doses of viable granulocytes has thus become an important approach for circumventing the problem. A schedule for collecting therapeutic numbers of cells with minimal donor toxicity has yet to be established. STUDY DESIGN AND METHODS: An investigation of three mobilization schedules for the collection of granulocytes for transfusion–granulocyte-colony-stimulating factor (G-CSF) 5 micrograms per kg daily; G-CSF 5 micrograms per kg every other day, and prednisone 60 mg given orally (20 mg doses at 17 hours, 12 hours, and 2 hours before the collection). RESULTS: A total of 464 apheresis procedures involving 163 healthy donors were analyzed. Prednisone caused a small increase in the white cell (WBC) counts over the collection days, while G-CSF every other day and daily schedules improved WBC counts to 145 and 160 percent, respectively (p = 0.004). Similarly, administration of G-CSF daily and every other day mobilized higher yields of granulocytes over the collection days, compared to the prednisone schedule (170% and 180% vs. 105%; p = 0.02). CONCLUSION: Compared with prednisone, higher WBC yields were achieved by G-CSF stimulation; G-CSF given every other day is as effective as daily G-CSF administration for the recruitment of granulocytes, which makes the mobilization procedure more cost- effective.     

Optimization of CD34+ collection for autologous transplantation using the evolution of peripheral blood cell counts after mobilization with chemotherapy and G-CSF.

BACKGROUND: Peripheral blood progenitor cells (PBPC) collection after high dose chemotherapy can be influenced by several factors. We searched for parameters that may predict the best day to start harvesting of PBPC in order to collect most CD34+ cells with the least number of aphereses. METHODS: We studied patients who underwent mobilization chemotherapy for autologous transplantation. The influence of age, sex, diagnosis, number of previous chemotherapy cycles, peripheral blood (PB) counts at day of mobilization (D0), day of neutrophils <1.0 x 10(9) l(-1) and day of nadir and interval between both (delta) on harvesting was investigated. Multivariate linear correlation models were built to predict the best harvesting with principles of parsimony. In patients where sequential CD34+ cell count was performed, the theoretical day of peak was calculated by interpolation in polynomial regression. RESULTS: One hundred and thirty four patients entered the analysis: 36 Hodgkin's lymphoma (HL), 65 B-large cell lymphoma (NHL) and 33 multiple myeloma (MM). Day of harvesting correlated with nr CHT, hemoglobin on D0, day of granulocytes <1.0 x 10(9) l(-1), delta and dosis of mobilization therapy. The day of CD34+ peak could be calculated by the formula = (-0.41) x Hemoglobin D0 + (day peripheral CD34+ cells = 10 x 10(6) microl(-1)) x 0.99 + 7.8. This model could explain 81% of the variance of the peak day and was stable by bootstrap resampling. Day of peripheral CD34+ cells = 10 x 10(6) microl(-1) preceded the calculated peak by 3-9 days. CONCLUSIONS: Although the day of best collection can be predicted using only sequential PB counts after mobilization chemotherapy, a model of prediction using peripheral CD34+ cell count is important especially for optimizing collection in poor mobilizing patients.     

托烷司琼复合氟哌啶醇与托烷司琼单用预防术后恶心呕吐的比较

目的:比较托烷司琼复合氟哌啶醇与单独使用托烷司琼预防术后恶心呕吐(PONV)的效果.方法:选择全身麻醉下行上腹部手术患者266例,随机分为托烷司琼组(T组)和托烷司琼复合氟哌啶醇组(T + H组).采用随机双盲法于手术结束前30 min给每位受试者静脉注射托烷司琼2 mg和试验用药1 mL(可能是1 mg氟哌啶醇或1 mL生理盐水),术后采用视觉模拟评分法(VAS)评估PONV程度.手术结束后记录恶心、干呕、呕吐和两组止吐药物治疗的情况,同时记录有无烦躁、谵妄、肌张力障碍、不能静坐和锥体外系反应.结果:术后恶心发生率T组37.6%,T + H组12.0%,T + H组明显低于T组(P ＜ 0.05);术后呕吐或干呕的发生率T组11.3%,T + H组4.5%,T + H组明显低于T组(P ＜ 0.05).T + H组预防PONV的疗效明显高于T组(P ＜ 0.05),只有少数恶心患者需给予止吐药物治疗.两组手术前后Q-T间期差异无统计学意义,两组中均未出现烦躁、谵妄、肌张力障碍、不能静坐和锥体外系反应患者.结论:托烷司琼复合氟哌啶醇对于预防PONV的效果和时程明显优于单独使用托烷司琼,且不增加不良反应的发生率.     

Successful mobilization of peripheral blood HPCs with G-CSF alone in patients failing to achieve sufficient numbers of CD34+ cells and/or CFU-GM with chemotherapy and G-CSF

BACKGROUND: Mobilization with chemotherapy and G-CSF may result in poor peripheral blood HPC collection, yielding <2 x 10(6) CD34+ cells per kg or <10 x 10(4) CFU-GM per kg in leukapheresis procedures. The best mobilization strategy for oncology patients remains unclear. STUDY DESIGN AND METHODS: In 27 patients who met either the CD34 (n = 3) or CFU-GM (n = 2) criteria or both (n = 22), the results obtained with two successive strategies-that is, chemotherapy and G-CSF at 10 microg per kg (Group 1, n = 7) and G-CSF at 10 microg per kg alone (Group 2, n = 20) used for a second mobilization course-were retrospectively analyzed. The patients had non-Hodgkin's lymphoma (5), Hodgkin's disease (3), multiple myeloma (5), chronic myeloid leukemia (1), acute myeloid leukemia (1), breast cancer (6), or other solid tumors (6). Previous therapy consisted of 10 (1-31) cycles of chemotherapy with additional chlorambucil (n = 3), interferon (n = 3), and radiotherapy (n = 7). RESULTS: The second collection was undertaken a median of 35 days after the first one. In Group 1, the results of the two mobilizations were identical. In Group 2, the number of CD34+ cells per kg per apheresis (0.17 [0.02-0.45] vs. 0.44 [0.11-0.45], p = 0. 00002), as well as the number of CFU-GM (0.88 [0.00-13.37] vs. 4.19 [0.96-21.61], p = 0.00003), BFU-E (0.83 [0.00-12.72] vs. 8.81 [1. 38-32.51], p = 0.00001), and CFU-MIX (0.10 [0.00-1.70] vs. 0.56 [0. 00-2.64], p = 0.001134) were significantly higher in the second peripheral blood HPC collection. However, yields per apheresis during the second collection did not significantly differ in the two groups. Six patients in Group 1 and 18 in Group 2 underwent transplantation, and all but one achieved engraftment, with a median of 15 versus 12 days to 1,000 neutrophils (NS), 22 versus 16 days to 1 percent reticulocytes (NS), and 26 versus 26 days to 20,000 platelets (NS), respectively. However, platelet engraftment was particularly delayed in many patients. CONCLUSION: G-CSF at 10 microg per kg alone may constitute a valid alternative to chemotherapy and G-CSF to obtain adequate numbers of peripheral blood HPCs in patients who previously failed to achieve mobilization with chemotherapy and G-CSF. This strategy should be tested in prospective randomized trials.     

A comparison of chemo-free strategy with G-CSF plus plerixafor on demand versus intermediate-dose cyclophosphamide and G-CSF as PBSC mobilization in newly diagnosed multiple myeloma patients: An Italian explorative cost Analysis

BackgroundUpfront single or tandem ASCT still represents an integral part of treatment for patients with multiple myeloma. The combination of intermediate dose (ID) - cyclophosphamide plus G-CSF, has been considered the standard method as mobilization regimen. No prospective randomized clinical trials have compared efficacy and costs using ID - cyclophosphamide against a chemo-free mobilization strategy with G-CSF and plerixafor on demand.MethodsA prospective single arm of 20 patients enrolled in three Italian Centers mobilized with G-CSF plus plerixafor on demand was compared with a retrospective historical control arm of 30 patients mobilized with ID - cyclophosphamide (4 g/sqm) and G-CSF. Costs of the prospective arm was compared with the ones of the retrospective control arm with the aim to collect ≥4 × 10⁶/kg CD34 + . The exploratory cost analysis was performed using microcosting specific inputs of G-CSF plus plerixafor on demand versus ID - cyclophosphamide + G-CSF considering pre-apheresis, peri-apheresis and post-apheresis session.ResultsMobilization with ID - cyclophosphamide and G-CSF resulted in a significantly higher CD34+ peak mean on day 1 yield (119 CD34+ μL vs 67.3; p = 0.06) and in total average CD34+ yield (mean collection 10.6 × 10⁶/kg vs 5.8 × 10⁶/kg; p = 0.004) compared to patients mobilized with G-CSF and plerixafor. There was no significant differences (p = 0.36) in the two groups of patients collecting ≥ 4 million CD34+/Kg with ID - cyclophosphamide and G-CSF (93.3 %) vs G-CSF and plerixafor (90.0 %). None of the patients undergoing G-CSF and plerixafor mobilization had febrile neutropenia compared with 7 patients who received ID - cyclophosphamide and G-CSF (0% vs 23 %, p = 0.03) who had a median of 5 days hospitalization (range 4–6). All patients proceeded to ASCT with a mean of 3.6 CD34+/kg infused for G-CSF and plerixafor arm and 4.4 CD34+/kg for the ID - cyclophosphamide + GCSF group (p = 0.37) with a median time to ANC and PLT engraftment not different in the two groups. Total costs of a mobilizing strategy using a combination of G-CSF and plerixafor on demand was 12.690 euros compared to 16.088 euros with ID - cyclophosphamide and G-CSF (p = 0.07); in particular, mobilization cost components were significantly lower for G-CSF and plerixafor vs G-CSF and ID - cyclophosphamide for hospital stay (3080 euros vs 9653 euros; p < 0.001) whereas for mobilizing agent, there was a significative difference with 5470 euros for G-CSF and plerixafor use due to the cost of plerixafor compared with 1140 euros for ID - cyclophosphamide and G-CSF treatment (P = 0.001).ConclusionsOur data demonstrate that in patients with multiple myeloma eligible for ASCT, a chemo-free mobilization with G-CSF and plerixafor on demand is associated with efficacy in PBSC collection and optimal safety profile with similar average costs when compared to a chemo-mobilization with ID - cyclophosphamide. A prospective randomized multicenter study could address which is the most cost-effective strategy for this setting of patients.Clinical Trial RegistryEudract Number EudraCT 2013−004690-27.     

AMD3100及联合G-CSF对小鼠淋巴细胞免疫功能的影响

目的 探讨基质细胞衍生因子受体CXCR4阻断剂AMD3100(plerixafor)单独或与G-CSF联合应用对小鼠脾脏淋巴细胞增殖能力及其对肿瘤细胞杀伤作用的影响.方法 以C57BL/6(H-2b)小鼠为供鼠,应用CCK-8分别检测AMD3100、G-CSF、AMD3100联合G-CSF及生理盐水动员后各组供鼠脾脏淋巴细胞经丝裂原诱导的增殖活性,及其与受鼠BALB/C(H-2b)小鼠脾脏淋巴细胞之间的混合淋巴细胞反应;应用LDH释放法检测上述各组供鼠脾脏淋巴细胞对淋巴瘤细胞株Yac-1细胞的杀伤功能.结果 与生理盐水对照组(1.86±0.07及1.58±0.15)相比,AMD3100动员组(1.23±0.04及1.18±0.05)、G-CSF动员组(1.19±0.05及1.17±0.04)及AMD3100联合G-CSF动员组(1.11±0.04及1.03±0.04)小鼠脾脏淋巴细胞的增殖能力、对异种抗原的反应能力均降低(P值均<0.05),AMD3100联合G-CSF动员组较其他各组降低更为明显,差异有统计学意义(P值均<0.05).在效靶比为40:1时,AMD3100动员组[(5.69±0.25)%]、G.CSF动员组[(5.63±0.29)%]及AMD3100联合G.CSF动员组[(5.76±0.24)%]小鼠脾脏淋巴细胞对肿瘤细胞的杀伤作用均较生理盐水对照组[(5.98±0.31)%]降低,但差异均无统计学意义(P值均>0.05).结论 AMD3100单独或与G-CSF联合应用后,小鼠脾脏淋巴细胞的增殖功能及对异种抗原的反应能力降低,而其对肿瘤细胞的杀伤功能未受明显影响,其作用机制有待深入研究.     

Bacterial adhesiveness: effects of the SH metabolite of erdosteine (mucoactive drug) plus clarithromycin versus clarithromycin alone

After metabolization, erdosteine (a mucoactive drug) produces an active metabolite (Met I) with an SH group that is capable of opening disulphide bonds, including those of pilin, a protein of bacterial fimbriae. This induces stereochemical conformational changes that interfere with the binding of bacterial adhesins (fimbriae) to receptors on eukaryotic cells. At subinhibitory concentrations, the macrolide clarithromycin inhibits the expression of adhesins on bacterial cell surfaces. The addition of 5 and 10 microg/ml of Met I to 1/8, 1/16 and 1/32 MIC of clarithromycin potentiated the inhibition of Staphylococcus aureus adhesiveness to human mucosal cells in comparison with the antibiotic alone. This finding opens up a new possibility of interfering with bacterial adhesiveness and its resulting pathogenicity not only by using antibiotics but also by means of their combination with agents devoid of antibacterial activity.     

Randomized, double-blind study of emtricitabine (FTC) plus clevudine versus FTC alone in treatment of chronic hepatitis B

Emtricitabine (FTC) is approved for the treatment of human immunodeficiency virus. FTC and clevudine (CLV) have activity against hepatitis B virus (HBV). This report summarizes the results of a double-blind, multicenter study of patients with chronic hepatitis B who had completed a phase 3 study of FTC and were randomized 1:1 to 200 mg FTC once daily (QD) plus 10 mg CLV QD or 200 mg FTC QD plus placebo for 24 weeks with 24 weeks of follow-up. One hundred sixty-three patients were treated (82 with FTC plus CLV [FTC+CLV] and 81 with FTC); 72% were men, 53% were Asian, 47% were Caucasian, and 52% were hepatitis B e antigen positive, and the median baseline HBV DNA level was 6 log(10) copies/ml. After 24 weeks of treatment, 74% (FTC+CLV) versus 65% (FTC alone) had serum HBV DNA levels of <4,700 copies/ml (P = 0.114) (Digene HBV Hybrid Capture II assay). Twenty-four weeks posttreatment, the mean change in serum HBV DNA levels from baseline was -1.25 log(10) copies/ml (FTC+CLV), 40% had undetectable viremia (versus 23% for FTC alone), and 63% had normal alanine aminotransferase levels (versus 42% for FTC alone) (P < or = 0.025 for all endpoints). The safety profile was similar between arms during treatment, with less posttreatment exacerbation of hepatitis B in the combination arm. In summary, after 24 weeks of treatment, no significant difference between arms was observed, but there was a significantly greater virologic and biochemical response 24 weeks posttreatment in the FTC+CLV arm.     

A multicenter randomized controlled trial of a 3-L/kg/min versus 2-L/kg/min high-flow nasal cannula flow rate in young infants with severe viral bronchiolitis (TRAMONTANE 2)

Purpose

High-flow nasal cannula (HFNC) therapy is increasingly proposed as first-line respiratory support for infants with acute viral bronchiolitis (AVB). Most teams use 2 L/kg/min, but no study compared different flow rates in this setting. We hypothesized that 3 L/kg/min would be more efficient for the initial management of these patients.

Methods

A randomized controlled trial was performed in 16 pediatric intensive care units (PICUs) to compare these two flow rates in infants up to 6 months old with moderate to severe AVB and treated with HFNC. The primary endpoint was the percentage of failure within 48 h of randomization, using prespecified criteria of worsening respiratory distress and discomfort.

Results

From November 2016 to March 2017, 142 infants were allocated to the 2-L/kg/min (2L) flow rate and 144 to the 3-L/kg/min (3L) flow rate. Failure rate was comparable between groups: 38.7% (2L) vs. 38.9% (3L; p?=?0.98). Worsening respiratory distress was the most common cause of failure in both groups: 49% (2L) vs. 39% (3L; p?=?0.45). In the 3L group, discomfort was more frequent (43% vs. 16%, p?=?0.002) and PICU stays were longer (6.4 vs. 5.3 days, p?=?0.048). The intubation rates [2.8% (2L) vs. 6.9% (3L), p?=?0.17] and durations of invasive [0.2 (2L) vs. 0.5 (3L) days, p?=?0.10] and noninvasive [1.4 (2L) vs. 1.6 (3L) days, p?=?0.97] ventilation were comparable. No patient had air leak syndrome or died.

Conclusion

In young infants with AVB supported with HFNC, 3 L/kg/min did not reduce the risk of failure compared with 2 L/kg/min. This clinical trial was recorded on the National Library of Medicine registry (NCT02824744).

     

Hemolytic transfusion reactions after administration of intravenous immune (gamma) globulin: a case series analysis

BACKGROUND: This case series summarizes our observations of hemolytic reactions after the administration of large amounts of intravenous immune (gamma) globulin (IVIG). STUDY DESIGN AND METHODS: Cases of hemolysis were identified by a decrease in hemoglobin not otherwise explained following IVIG administration. RESULTS: Sixteen cases were identified over a 2 1/2-year period at the Ottawa Hospital of approximately 1000 patients receiving IVIG (1.6%). Characteristics of these patients include a large dose of IVIG, female sex, non-O blood group, and underlying inflammatory state. CONCLUSIONS: Significant hemolysis may occur after the administration of large doses of IVIG. A two-step mechanism of hemolysis is proposed, sensitization by ABO isohemagglutinins followed by phagocytosis by activated macrophages. A simple protocol to facilitate the early detection of such cases is presented.     

Collection of peripheral blood stem cells (PBSC) after chemotherapy and administration of rhGM-CSF in children weighing less than 17 kg

Peripheral blood stem cells (PBSC) were collected from six children weighing less than 17 kg. Stem cell pools had been expanded by chemotherapy and rhGM-CSF. Nineteen procedures were performed with a continuous-flow separator (CS 3000 plus) using central venous access. The extracorporeal line was primed with red blood cells and 5% albumin (HA). Acid-citrate-dextrose:- formulae A(ACD-A) was added in a median ratio 1:11 (range 1:9-1:15). A median number of 5.6 x 10(8) kg-1 NC (3.5-9.7) and 7.1 x 10(6) kg-1 CD34+ cells (2.1-26.1) were collected per patient. Four patients were transplanted with PBSC and showed normal haematopoietic recovery (leucocytes > 1000 microL-1 between days 11 and 12). The results show that successful PBSC collection and transplantation is possible even in small paediatric patients. Administration of growth factors results in a marked increase of peripheral white blood cells and in a higher yield of NC and CD34+ cells in PBSC collections.     

Plerixafor and granulocyte-colony-stimulating factor (G-CSF) in patients with lymphoma and multiple myeloma previously failing mobilization with G-CSF with or without chemotherapy for autologous hematopoietic stem cell mobilization: the Austrian experience on a named patient program

BACKGROUND: Plerixafor in combination with granulocyte–colony‐stimulating factor (G‐CSF) has been shown to enhance stem cell mobilization in patients with multiple myeloma, non‐Hodgkin's lymphoma, and Hodgkin's disease who demonstrated with previous mobilization failure. In this named patient program we report the Austrian experience in insufficiently mobilizing patients. STUDY DESIGN AND METHODS: Twenty‐seven patients from eight Austrian centers with a median (range) age of 58 (19‐70) years (18 female, nine male) were included in the study. Plerixafor was limited to patients with previous stem cell mobilization failure and was given in the evening of Day 4 of G‐CSF application. RESULTS: A median increase of circulating CD34+ cells within 10 to 11 hours from administration of plerixafor by a factor of 4.7 over baseline was noted. Overall, 20 (74%) patients reached more than 10 × 10⁶ CD34+ cells/L in the peripheral blood, resulting in 17 (63%) patients collecting at least 2 × 10⁶ CD34+ cells/kg body weight (b.w.; median, 2.6 × 10⁶ CD34+ cells/kg b.w.; range, 0.08 × 10⁶‐8.07 × 10⁶). Adverse events of plerixafor were mild to moderate and consisted of gastrointestinal side effects and local reactions at the injection site. Thirteen (48%) patients underwent autologous transplantation receiving a median of 2.93 × 10⁶ CD34+ cells/kg (range, 1.46 × 10⁶‐5.6 × 10⁶) and showed a trilinear engraftment with a median neutrophil recovery on Day 12 and a platelet recovery on Day 14. CONCLUSION: Our study confirms previous investigations showing that plerixafor in combination with G‐CSF is an effective and well‐tolerated mobilization regimen with the potential of successful stem cell collection in patients with previous mobilization failure.