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1.
A randomized, double-blind, phase 2 study of erythropoietin in optic neuritis
Suhs KW, Hein K, Sattler MB, Gorlitz A, Ciupka C, Scholz K, et al.,
Annals of Neurology. 2012;72((2):):199-210.
Abstract
OBJECTIVE Based on findings in animal models of autoimmune optic nerve inflammation, we have assessed the safety and efficacy of erythropoietin in patients presenting with a first episode of optic neuritis. METHODS Patients with optic neuritis who attended the University Hospitals of Homburg/Saar, Göttingen, or Hamburg (Germany) were included in this double-blind, placebo-controlled, phase 2 study (ClinicalTrials.gov, NCT00355095). They were randomly assigned to groups receiving either 33,000IU recombinant human erythropoietin intravenously daily for 3 days or placebo as an add-on therapy to methylprednisolone. The primary outcome parameter was change in retinal nerve fiber layer (RNFL) thickness after 16 weeks. Secondary outcome parameters included optic nerve atrophy as assessed by magnetic resonance imaging, and changes in visual acuity, visual field, and visual evoked potentials (VEPs). RESULTS Forty patients were assigned to the treatment groups (21/19 erythropoietin/placebo). Safety monitoring revealed no relevant issues. Thirty-seven patients (20/17 erythropoietin/placebo) were analyzed for the primary endpoint according to the intention-to-treat protocol. RNFL thinning was less apparent after erythropoietin treatment. Thickness of the RNFL decreased by a median of 7.5µm by week 16 (mean ± standard deviation, 10.55 ± 17.54µm) compared to a median of 16.0µm (22.65 ± 29.18µm) in the placebo group (p = 0.0357). Decrease in retrobulbar diameter of the optic nerve was smaller in the erythropoietin group (p = 0.0112). VEP latencies at week 16 were shorter in erythropoietin-treated patients than in the placebo group (p = 0.0011). Testing of visual functions revealed trends toward an improved outcome after erythropoietin treatment. INTERPRETATION These results give the first indications that erythropoietin might be neuroprotective in optic neuritis. Copyright © 2012 American Neurological Association.
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2.
Management of chronic childhood immune thrombocytopenic purpura: AIEOP consensus guidelines
De Mattia D, Del Vecchio GC, Russo G, De Santis A, Ramenghi U, Notarangelo L,, et al.,
Acta Haematologica. 2010;123((2):):96-109.
Abstract
Background/Objective: The management of chronic childhood idiopathic thrombocytopenic purpura (ITP) is distinct from acute ITP. Similar to the publication on acute ITP guidelines, the AIEOP (Associazione Italiana di Ematologia e Oncologia Pediatrica) considered it appropriate to develop consensus guidelines for chronic childhood ITP to provide useful and shared information for physicians, healthcare professionals, parents and patients. Design/Methods: A preliminary, evidence-based document issued by a select group of AIEOP pediatric hematologists was discussed, modified and approved during a Consensus Conference according to procedures previously validated by the AIEOP Board. Results: The guidelines give prominence to the periodical reevaluation of all the etiological hypotheses of thrombocytopenia in relation to its clinical condition. The majority of chronic ITP children do not require treatment, especially if bleeding is absent or minimal. The treatment decision depends on several factors other than the platelet count, and treatment options are suggested in relation to the therapeutic scenarios. Recommendations are given regarding support for surgery, particular hemorrhagic conditions, daily activities/sports, as well as for vaccines and drugs. Experimental treatments are also discussed.
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3.
The clinical usefulness of high-dose intravenous immunoglobulin therapy for chronic inflammatory demyelinating polyneuropathy and multifocal motor neuropathy Japanese
Kubori T, Mezaki T, Kaji R, Kimura J, Hamaguchi K, Hirayama K, Kanazawa I, Miyatake T, Mannen T, Kowa H, et al
No to Shinkei [Brain & Nerve]. 1999;51((2):):127-35.
Abstract
To explore the optimum dose of intravenous immunoglobulin (i.v.Ig) for treating patients with chronic inflammatory demyelinating polyrneuropathy and multifocal motor neuropathy, we compared the usefulness of i.v.Ig among 3 treatment doses. Fifty-nine patients were randomly divided into three treatment dosage groups: 20 patients for Group I using 50 mg/kg/day x 5 days, 19 patients Group II using 200 mg/kg/day x 5 days, and 20 patients Group III using 400 mg/kg/day x 5 days. We assessed clinically and electrophysiologically the effectiveness of the treatment at 5 weeks after the initial infusion. For patients in Group I and II who had not improved (or worsened) with the first treatment, we gave a one-step larger dose in the second treatment (i.e. 200 mg/kg/day x 5 days for those who had been given 50 mg/kg/day x 5 days, 400 mg/kg/day x 5 days for those who had been given 200 mg/kg/day x 5 days) after more than 9 weeks. We found that 15% of the patients in Group I, 21% in Group II and 60% in Group III improved dose-dependently with the first intravenous immunoglobulin treatment. Seven (47%) of 16 patients in Group I and 4 (40%) of 11 patients in Group II improved after the second treatment with larger doses. Adverse reactions including chill sensation, fever, skin eruption and increase in blood GOT and GPT levels were transient and mild. One patient in Group III developed left hemiparesis showing the small infarction in the right thalamus during the course of the treatment, but the symptom was mild. In conclusion, the high-dose intravenous immunoglobulin therapy (400 mg/kg/day x 5 days) is useful for treating patients with CIDP and MMN, although care must be taken of the risk of causing cerebral infarctions.
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4.
Stroke prevention trial in sickle cell anemia
Adams RJ, McKie VC, Brambilla D, Carl E, Gallagher D, Nichols FT, Roach S, Abboud M, Berman B, Driscoll C, et al
Controlled Clinical Trials. 1998;19((1):):110-29.
Abstract
Stroke occurs in 7-8% of children with Sickle Cell Disease (Hb SS) and is a major cause of morbidity. Rates of recurrence have been reduced from 46-90% to less than 10% through chronic blood transfusions. Prevention of first stroke, however, would be preferable because even one stroke can cause irreversible brain injury. Transcranial Doppler (TCD) ultrasound can detect arterial blood flow rates associated with subsequent stroke risk. By combining TCD screening and a potentially effective treatment, first stroke may be prevented. The Stroke Prevention Trial in Sickle Cell Anemia (STOP) is the first stroke prevention trial in Hb SS and the first randomized, controlled use of transfusion in Hb SS. This multi-center trial is designed to test whether reducing sickle hemoglobin to 30% or less with periodic blood transfusions will reduce first-time stroke by at least 70% compared to standard care. Primary endpoints will be clinically evident symptoms of cerebral infarction with consistent findings on Magnetic Resonance Imaging and Angiography (MRI/MRA) or symptomatic intracranial hemorrhage. Secondary endpoints will be asymptomatic brain lesions detected by MRI in brain areas not involved in primary endpoints. The design calls for a 6-month start-up interval, 18 months of TCD screening and randomization, and observation for stroke from entry through month 54. Key features of the trial are standardized TCD and MRI/MRA protocols interpreted blindly, and blinded adjudication of endpoints. The sample size (60 per treatment group) is based on prospective data relating TCD velocity to risk of stroke. A time-averaged mean velocity of > or = 200 cm/sec is associated with a 46% risk of cerebral infarction over 39 months. The sample size is sufficient to detect 70% reduction in the primary endpoint at 90% power. This trial will determine if transfusion is effective in the primary prevention of stroke. Secondary aims may further the understanding of the effects of transfusion on the brain and guide future research into cerebrovascular disease in Hb SS.
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5.
Immunoprophylaxis against klebsiella and pseudomonas aeruginosa infections. The Federal Hyperimmune Immunoglobulin Trial Study Group
Donta ST, Peduzzi P, Cross AS, Sadoff J, Haakenson C, Cryz SJ Jr, Kauffman C, Bradley S, Gafford G, Elliston D, et al
Journal of Infectious Diseases. 1996;174((3):):537-43.
Abstract
To determine if passive immunization could decrease the incidence or severity of Klebsiella and Pseudomonas aeruginosa infections, patients admitted to intensive care units of 16 Department of Veterans Affairs and Department of Defense hospitals were randomized to receive either 100 mg/kg intravenous hyperimmune globulin (IVIG), derived from donors immunized with a 24-valent Klebsiella capsular polysaccharide plus an 8-valent P. aeruginosa O-polysaccharide-toxin A conjugate vaccine, or an albumin placebo. The overall incidence and severity of vaccine-specific Klebsiella plus Pseudomonas infections were not significantly different between the groups receiving albumin and IVIG. There was some evidence that IVIG may decrease the incidence (2.7% albumin vs. 1.2% IVIG) and severity (1.0% vs. 0.3%) of vaccine-specific Klebsiella infections, but these reductions were not statistically significant. The trial was stopped because it was statistically unlikely that IVIG would be protective against Pseudomonas infections at the dosage being used. Patients receiving IVIG had more adverse reactions (14.4% vs. 9.2%).
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6.
Use of cytomegalovirus immunoglobulin in multiply transfused premature neonates
Snydman DR, Werner BG, Meissner HC, Cheeseman SH, Schwab J, Bednarek F, Kennedy JL Jr, Herschel M, Magno A, Levin MJ,, et al
Pediatric Infectious Disease Journal. 1995;14((1):):34-40.
Abstract
We undertook a randomized, placebo-controlled, double blind trial of cytomegalovirus (CMV) immunoglobulin (CMVIG) for prevention of CMV-associated disease in 183 multiply transfused, premature neonates. CMVIG (150 mg/kg) or placebo was given within 24 hours of the first transfusion and at Day 10. If an intravenous catheter was still in place an additional dose was given between Days 20 and 30. The globulin and placebo groups were well-matched with respect to birth weight, gestational age, Apgar score, birth to a CMV-seropositive mother, requirement for assisted ventilation and exposure to CMV-positive, unscreened blood products. Among infants followed for more than 10 days, 18 (10.5%) developed CMV infection; 9 had symptomatic CMV disease (5 placebo; 4 CMVIG). Among infants born to a CMV-seropositive mother, CMVIG use was associated with a CMV syndrome rate of 3.2% (95% confidence interval, 0.2 to 18.5%) compared to 12.5% (95% confidence interval, 4.5 to 27.6%) among placebo recipients (P = 0.163). Among placebo recipients infants born to CMV-seropositive mothers were more likely to have a virologically confirmed CMV syndrome than those born to a CMV-seronegative mother, despite receipt of blood not screened for CMV antibody (P = 0.012). Multivariate analysis demonstrated that two factors were independently associated with CMV acquisition: the volume of CMV-seropositive blood products transfused (P = 0.005); and birth to a CMV-seropositive mother (P = 0.006). Infusions of CMVIG were well-tolerated. This study reaffirms that perinatally acquired CMV disease is more common among infants born to CMV-seropositive mothers than CMV-seronegative mothers, even without use of CMV-screened blood products.
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7.
Recombinant human erythropoietin stimulates erythropoiesis and reduces erythrocyte transfusions in very low birth weight preterm infants
Shannon KM, Keith JF 3rd, Mentzer WC, Ehrenkranz RA, Brown MS, Widness JA, Gleason CA, Bifano EM, Millard DD, Davis CB,, et al
Pediatrics. 1995;95((1):):1-8.
Abstract
DESIGN AND METHODS We hypothesized that treatment with recombinant human erythropoietin (r-HuEPO) would stimulate erythropoiesis and would thereby reduce the need for erythrocyte transfusions in preterm infants. We treated 157 preterm infants born at 26.9 +/- 1.6 weeks of gestation who weighed 924 +/- 183 g at birth with either subcutaneous r-HuEPO (100 U/kg/d, 5 days per week) or placebo for 6 weeks in a randomized, double-blind, controlled clinical trial. All patients received oral iron and were managed according to uniform conservative transfusion guidelines. RESULTS Treatment with r-HuEPO was associated with fewer erythrocyte transfusions (1.1 +/- 1.5 per infant in the r-HuEPO group versus 1.6 +/- 1.7 per infant in the placebo group; P = .046) and with a reduction in the volume of packed erythrocytes transfused (16.5 +/- 23.0 mL versus 23.9 +/- 25.7 mL per infant; P = .023). Overall, 43% of the infants in the r-HuEPO group and 31% of placebo-treated infants were transfusion-free during the study (P = .18). The volume of blood removed for laboratory tests and the need for respiratory support at the start of treatment had major effects on transfusion requirements independent of r-HuEPO. Reticulocyte counts were higher during treatment in the r-HuEPO group (P = .0001), and r-HuEPO-treated infants had higher hematocrit values at the end of the study (32% versus 27.3% in the placebo group; P = .0001). We found no differences in the incidence of major complications of prematurity between the treatment groups. CONCLUSION We conclude that treatment with r-HuEPO at a weekly dose of 500 U/kg stimulates erythropoiesis, moderates the course of anemia, is associated with a reduction in erythrocyte transfusions, and appears safe in very low birth weight preterm infants who are receiving iron supplements. Conservative transfusion criteria, minimization of phlebotomy losses, and treatment with r-HuEPO are complementary strategies to reduce erythrocyte transfusions in these infants.
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8.
White cell reduction in platelet concentrates and packed red cells by filtration: a multicenter clinical trial. The Trap Study Group
Kao KJ, Mickel M, Braine HG, Davis K, Enright H, Gernsheimer T, Gillespie MJ, Kickler TS, Lee EJ, McCullough JJ,, et al
Transfusion. 1995;35((1):):13-9.
Abstract
BACKGROUND Most previous studies on white cell (WBC) reduction by filtration have been small-scale studies conducted under tightly controlled laboratory conditions. Their results would be the ideal, rather than what might be expected during routine operation. STUDY DESIGN AND METHODS To obtain information on routine filtration of blood components, data have been collected from a large-scale, ongoing, multicenter clinical trial designed to determine the effectiveness of WBC reduction in or ultraviolet B radiation of platelet concentrates before transfusion in preventing platelet alloimmunization and platelet transfusion refractoriness. The WBC content of blood components both before and after filtration was determined by automated cell counters and a manual propidium iodide-staining method, respectively. Platelet and red cell losses during filtration were measured. RESULTS The average platelet losses after filtration were 24 +/- 15 percent and 20 +/- 9 percent for apheresis platelets and pooled platelets, respectively. The frequencies at which filtered platelet concentrates contained high levels of residual WBCs (> 5 x 10(6)) were 7 percent and 5 percent for apheresis platelets and pooled platelets, respectively. Further analysis of the platelet filtration data showed that greater numbers of total initial WBCs in the pooled platelets were associated with increased percentages of filtration failure (> 5 x 10(6) residual WBCs). For packed red cells, the average losses during filtration were 23 +/- 4 percent and 15 +/- 3 percent for CPDA-1 units and Adsol units, respectively. The frequencies at which filtered red cells contained > 5 x 10(6) residual WBCs were 2.7 percent for one type of filter and 0.3 percent for another type of filter. CONCLUSION There were significant losses of platelets during filtration, which could add to the costs of WBC reduction and lead to possible increases in donor exposures. Filtration failures still occurred, despite careful observation of the standard filtration procedures. The number of total WBCs in pooled platelets before filtration has been identified as an important factor in determining the success of WBC reduction.
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9.
Pharmacokinetics and tolerability of factor XIII concentrates prepared from human placenta or plasma: a crossover randomised study
Brackmann HH, Egbring R, Ferster A, Fondu P, Girardel JM, Kreuz W, Masure R, Miloszewski K, Stibbe J, Zimmermann R,, et al
Thrombosis & Haemostasis. 1995;74((2):):622-5.
Abstract
The pharmacokinetics and tolerability of factor XIII (FXIII) from plasma were compared with those of FXIII from placenta in a randomised, double-blind, crossover study involving 13 patients with congenital FXIII deficiency. Both FXIII activity and FXIII antigen were monitored. No difference was seen in the mean half-lives of the two preparations (9.3 days and 9.1 days for plasma and placenta FXIII activity, respectively). Response was similar for both preparations, but was slightly greater for FXIII from plasma (1.6 ormula: see text] vs 1.5 [formula: see text]). Similar results were found for recovery (65% vs 60%). The area under the data completed by extrapolation was significantly higher for FXIII from plasma. No differences between preparations in terms of efficacy or tolerability were observed. It can be concluded that treatment with FXIII concentrate from plasma is as efficient as with FXIII concentrate from placenta in terms of recovery and half-life. Both preparations were equivalent in terms of safety during the observation period. With the administration of monthly injections of approximately 30 U/kg serious bleeding events were prevented and no other serious adverse events occurred.
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10.
Passive immunotherapy in AIDS: a double-blind randomized study based on transfusions of plasma rich in anti-human immunodeficiency virus 1 antibodies vs. transfusions of seronegative plasma
Vittecoq D, Chevret S, Morand-Joubert L, Heshmati F, Audat F, Bary M, Dusautoir T, Bismuth A, Viard JP, Barre-Sinoussi F,, et al
Proceedings of the National Academy of Sciences of the United States of America. 1995;92((4):):1195-9.
Abstract
A randomized double-blind controlled trial was conducted to determine the efficacy of passive immunotherapy in the treatment of symptomatic human immunodeficiency virus (HIV) infection. This trial included 86 symptomatic patients randomized to receive plasma rich in anti-HIV-1 antibody or standard seronegative plasma. Each patient in both groups received a 300-ml infusion every 14 days over a 1-year period, and every 28 days thereafter, in addition to zidovudine and other conventional prophylactic treatments. Plasma donors were selected among symptomless seropositive individuals with a CD4 lymphocyte count > or = 400 x 10(6) cells per liter, a negative p24 antigen assay, and a high concentration of anti-p24 antibody. The plasmas were heat-inactivated before infusion. During the study period (day 28-day 365) scheduled by the protocol, clinical benefit from passive immunotherapy was observed in delaying the appearance of the first AIDS-defining event (P < 0.009) and reducing the cumulative incidence of such events, which was estimated 3-fold higher in the control group compared to the treatment group. Seven deaths occurred in the treatment group vs. 11 in the control group (P = 0.27). A total of 47 patients died or exhibited new AIDS-defining events, 18 in the treatment group and 29 in the control group (P = 0.009). No clinical benefit was observed after the 1-year period with infusions performed every 4 weeks. These results indicate a favorable effect of passive immunotherapy on the evolution of advanced AIDS.