Dendritic cell vaccination as postremission treatment to prevent or delay relapse in acute myeloid leukemia.

Relapse is a major problem in acute myeloid leukemia (AML) and adversely affects survival. In this phase 2 study, we investigated the effect of vaccination with dendritic cells (DCs) electroporated with Wilms' tumor 1 (WT1) messenger RNA (mRNA) as postremission treatment in 30 patients with AML at very high risk of relapse. There was a demonstrable antileukemic response in 13 patients. Nine patients achieved molecular remission as demonstrated by normalization of WT1 transcript levels, 5 of which were sustained after a median follow-up of 109.4 months. Disease stabilization was achieved in 4 other patients. Five-year overall survival (OS) was higher in responders than in nonresponders (53.8% vs 25.0%; P = .01). In patients receiving DCs in first complete remission (CR1), there was a vaccine-induced relapse reduction rate of 25%, and 5-year relapse-free survival was higher in responders than in nonresponders (50% vs 7.7%; P < .0001). In patients age ≤65 and >65 years who received DCs in CR1, 5-year OS was 69.2% and 30.8% respectively, as compared with 51.7% and 18% in the Swedish Acute Leukemia Registry. Long-term clinical response was correlated with increased circulating frequencies of polyepitope WT1-specific CD8+ T cells. Long-term OS was correlated with interferon-γ+ and tumor necrosis factor-α+ WT1-specific responses in delayed-type hypersensitivity-infiltrating CD8+ T lymphocytes. In conclusion, vaccination of patients with AML with WT1 mRNA-electroporated DCs can be an effective strategy to prevent or delay relapse after standard chemotherapy, translating into improved OS rates, which are correlated with the induction of WT1-specific CD8+ T-cell response. This trial was registered at www.clinicaltrials.gov as #NCT00965224.

Correction to: Biological tests carried out on serum/plasma samples from donors of human body material for transplantation: Belgian experience and practical recommendations.

The article Biological tests carried out on serum/plasma samples from donors of human body material for transplantation: Belgian experience and practical recommendations.

Biological tests carried out on serum/plasma samples from donors of human body material for transplantation: Belgian experience and practical recommendations.

This paper on the biological tests carried out on serum/plasma samples from donors of human body material (HBM) is the result of a project of the working Group of Superior Health Council of Belgium formed with experts in the field of HBM and infectious serology. Indeed, uncertainty about the interpretation of biological test results currently leads to the sometimes unjustified cancelling of planned donations or the rejection of harvested HBM, whilst more sophisticated diagnostic algorithms would still allow the use of organs or HBM that would otherwise have been rejected. NAT tests will not be discussed in this publication. In the first part some general aspects as the need for a formal agreement between the Tissue Establishment l and the laboratory responsible for the biological testing, but also some specifications regarding testing material, the choice of additional biological tests, and some general aspects concerning interpretation and reporting are discussed. In a second part, detailed information and recommendations concerning the interpretation are presented for each of the mandatory tests (human immunodeficiency virus, hepatitis B virus, hepatitis C virus and syphilis) is presented. A number of not mandatory, but regularly used optional serological tests (e.g. for the detection of antibodies to Toxoplasma gondii, Epstein-Barr virus, human T cell leukemia virus and cytomegalovirus) are also extensively discussed. Although the project was meant to provide clarification and recommendations concerning the Belgian legislation, the majority of recommendations are also applicable to testing of donors of tissues and cells in other (European) countries.

Endoscopic versus transcranial procurement of allograft tympano-ossicular systems: a prospective double-blind randomized controlled audit.

Allograft tympano-ossicular systems (ATOS) have proven their use over many decades in tympanoplasty and reconstruction after resection of cholesteatoma. The transcranial bone plug technique has been used in the past 50 years to procure en bloc ATOS (tympanic membrane with malleus, incus and stapes attached). Recently, our group reported the feasibility of the endoscopic procurement technique. The aim of this study was to assess whether clinical outcome is equivalent in ATOS acquired by using the endoscopic procurement technique compared to ATOS acquired by using the transcranial technique. A double-blind randomized controlled audit was performed in a tertiary referral center in patients that underwent allograft tympanoplasty because of chronic otitis media with and without cholesteatoma. Allograft epithelialisation was evaluated at the short-term postoperative visit by microscopic examination. Failures were reported if reperforation was observed. Fifty patients underwent allograft tympanoplasty: 34 received endoscopically procured ATOS and 16 received transcranially procured ATOS. One failed case was observed, in the endoscopic procurement group. We did not observe a statistically significant difference between the two groups in failure rate. This study demonstrates equivalence of the clinical outcome of allograft tympanoplasty using either endoscopic or transcranial procured ATOS and therefore indicates that the endoscopic technique can be considered the new standard procurement technique. Especially because the endoscopic procurement technique has several advantages compared to the former transcranial procurement technique: it avoids risk of prion transmission and it is faster while lacking any noticeable incision.

Endoscopic procurement of allograft tympano-ossicular systems: valuable to replace the Schuknecht bone plug technique?

Recently, our group demonstrated the technical feasibility of allograft tympano-ossicular systems (ATOS) procurement directly through the external auditory canal by using a rigid endoscope. This novel technique has several advantages compared to the traditional transcranial Schuknecht bone plug technique: it avoids contact with the dura mater, it is less time-consuming and it doesn't require a thorough reconstruction of the donor. In our tissue bank, we are currently transitioning from the transcranial procurement technique to the endoscopic procurement technique. The learning curve to master the endoscopic technique is steep but our preliminary results suggest that the percentage of good quality endoscopically procured ATOS is at least similar to the percentage of good quality transcranially procured ATOS dissected from the temporal bone plug. Additionally, the number of donations has increased significantly. By avoiding contact with the dura mater and therefore eliminating the risk of potential prion disease transmission, this technical evolution in procurement technique might allow dedicated tissue banks to (re-)introduce ATOS procurement and implantation.

Endoscopic procurement of tympano-ossicular allografts: alternative to the transcranial or retroauricular technique.

A tympano-ossicular tissue bank complying with European Union regulations on human allografts is feasible and critical to assure that the patient receives tissue which is safe, individually checked and prepared in a suitable environment. The transcranial procurement technique has become the standard approach to procure tympano-ossicular allografts since the 1970s because it can provide en bloc allografts. Over the last 10-20 years, en bloc allografts have been abandoned and only the malleus (hammer) is left attached to the tympanic membrane. This modification enables introduction of the transmeatal procurement technique. Transmeatal procurement using readily available nasal 0° and 30° endoscopes is a feasible alternative which avoids contact with the dura mater and is not esthetically invasive to the donor. It involves a more time-consuming procurement but avoids the need for preparation of the temporal bone plug and is therefore generally more time-efficient.

Temporal bone bank: complying with European Union directives on human tissue and cells.

BACKGROUND: Availability of allograft tympano-ossicular systems (ATOS) provides unique reconstructive capabilities, allowing more radical removal of middle ear pathology. To provide ATOS, the University of Antwerp Temporal Bone Bank (UATB) was established in 1988. ATOS use was stopped in many countries because of safety issues concerning human tissue transplantation. Our objective was to maintain an ATOS tissue bank complying with European Union (EU) directives on human tissues and cells. METHODS: The guidelines of the Belgian Superior Health Council, including EU directive requirements, were rigorously applied to UATB infrastructure, workflow protocols and activity. Workflow protocols were updated and an internal audit was performed to check and improve consistency with established quality systems and changing legislations. The Belgian Federal Agency of Medicines and Health Products performed an inspection to examine compliance with national legislatives and EU directives on human tissues and cells. A sample of important procedures was meticulously examined in its workflow setting next to assessment of the infrastructure and personnel. RESULTS: Results are reported on infrastructure, personnel, administrative workflow, procurement, preparation, processing, distribution, internal audit and inspection by the competent authority. Donors procured: 2006, 93 (45.1%); 2007, 64 (20.6%); 2008, 56 (13.1%); 2009, 79 (6.9%). The UATB was approved by the Minister of Health without critical or important shortcomings. The Ministry accords registration each time for 2 years. CONCLUSIONS: An ATOS tissue bank complying with EU regulations on human allografts is feasible and critical to assure that the patient receives tissue, which is safe, individually checked and prepared in a suitable environment.

Bacterial detection of platelets: current problems and possible resolutions.

The greatest transfusion-transmitted disease risk facing a transfusion recipient is that of bacterial sepsis. The prevalence of bacterial contamination in platelets and red blood cells is approximately 1 in 3,000 units transfused. The available data indicate that transfusion-associated sepsis develops after 1 in 25,000 platelet transfusions and 1 in 250,000 red blood cell transfusions. One of the most widely used strategies for decreasing bacterial sepsis risk is bacterial detection. A roundtable meeting of experts was convened during the XXVIII Annual Congress of the International Society of Blood Transfusion (Edinburgh, UK, July 2004) to provide a forum for experts to share their experiences in the routine bacterial detection of platelet products. This article summarizes the presentations, discussions, and recommendations of the panel. The data presented indicate that some of the current bacterial screening technology is useful for blocking the issuance of platelet units that contain relatively high levels of contaminating bacteria. Platelet units are usually released based on a test-negative status, which often become test-positive only upon longer storage. These data thus suggest that bacterial screening may not prevent all transfusion-transmitted bacterial infections. Two transfusion-transmitted case reports further highlighted the limitation of the routine bacterial screening of platelet products. It was felt that newer technologies, such as pathogen inactivation, may represent a more reliable process, with a higher level of safety. The panel thus recommended that the Transfusion Medicine community may need to change its thinking (paradigm) about bacterial detection, toward the possibility of the pathogen inactivation of blood products, to deal with the bacterial contamination issue. It was suggested, where permitted by regulatory agencies, that blood centers should consider adopting first-generation pathogen inactivation systems as a more effective approach to reducing the risk of transfusion-associated sepsis than some of the approaches currently available.