The narrow therapeutic range and wide interpatient variability in dose requirement make anticoagulation response to coumarin derivatives unpredictable. As a result, patients require frequent monitoring to avert adverse effects and maintain therapeutic efficacy. Polymorphisms in VKORC1 and CYP2C9 jointly account for about 40% of the interindividual variability in dose requirements. To date, several pharmacogenetic-guided dosing algorithms for coumarin derivatives, predominately for warfarin, have been developed. However, the potential benefit of these dosing algorithms in terms of their safety and clinical utility has not been adequately investigated in randomized settings. The European Pharmacogenetics of Anticoagulant Therapy (EU-PACT) trial will assess, in a single-blinded and randomized controlled trial with a follow-up period of 3 months, the safety and clinical utility of genotype-guided dosing in daily practice for the three main coumarin derivatives used in Europe. The primary outcome measure is the percentage time in the therapeutic range for international normalized ratio. This report describes the design and protocol for the trial.
Summary:The number of infused cells is a very important factor in cord blood transplant (CBT) engraftment. Prior ex vivo expansion of aliquots of transplanted cord blood (CB) units is being investigated as a procedure to increase engraftment potential, but results are difficult to evaluate due to a lack of markers for assessing the contribution of expanded cells. We transplanted five patients, infusing the best available CB unit and cells from a second donor simultaneously. In two patients, these cells were obtained from another frozen CB unit by CD34+ positive selection and culture expansion; the other three patients received uncultured highly purified haploidentical CD34+ cells. The first two patients had DNA from the culture expanded CB cells detected only for a few days around day +11 when the absolute neutrophil count (ANC) was Ͻ200/l; thereafter and when the ANC was Ͼ500/l, only donor DNA from the uncultured CB was detected. For the other three patients, DNA analysis showed early and transient granulocyte engraftment of haploidentical cells, progressively replaced by the CB-derived granulocytes. We concluded that: (1)
Summary. Epstein-Barr virus associated lymphoproliferative disease after autologous bone marrow transplantation (ABMT) has rarely been reported. We report a case of Bcell lymphoma following ABMT for T-acute lymphoblastic leukaemia; bone marrow was purged in vitro with monoclonal antibodies to remove T cells. Immunoglobulin and T-cell receptor gene rearrangement studies were used to demonstrate clonality and to show that this patient developed a second neoplasm after ABMT. EBV proteins and genome (type A) were present in post-transplantation lymphoma, suggesting a causative role in its development.
Summary:One of the concerns about the use of cord blood as a source of hematopoietic stem cells for allogeneic transplantation is the possibility of contamination by maternal cells which could cause life-threatening GVHD. We have assessed cord blood contamination using PCR analysis of several minisatellite regions to detect maternal DNA. Eighty mother-cord pairs were obtained for this study. In one case there were no specific maternal alleles at any loci and, therefore, cord blood could not be evaluated. Thus, there was a total of 79 informative cases for the detection of maternal cells in the fetal circulation. In most cases, the level of detection was between 0.5 and 1%. We detected maternal DNA in the cord blood sample in only one case (1.26%), and the analysis of dilution experiments led to an estimate of 0.5-1% maternal cells. In conclusion, using PCR amplification of hypervariable regions, maternal DNA is very rarely detected in the cord blood collected at birth, although this approach has a relatively low level of sensitivity. Keywords: cord blood; maternal cell contamination; hematopoietic stem cell transplantation; minisatellite repeats; polymerase chain reaction Umbilical cord blood contains hematopoietic progenitor cells 1 that can be used as an acceptable alternative to bone marrow for clinical transplantation. 2 Although initial donors were siblings, more recently cord blood transplants from unrelated donors have been used, and international umbilical cord blood banks have already been established in Europe and in the USA.One of the remaining concerns about the use of cord blood in unrelated transplantation is the possibility of contamination by maternal cells; maternal T lymphocytes only partially matched with the histocompatibility antigens of the recipient could cause life-threatening GVHD after transplantation.The objective of this study was to determine the frequency and degree of cord blood contamination by Correspondence: Dr M Briz, Hospital Puerta de Hierro, San Martín de Porres 4, 28035-Madrid, Spain Received 4 November 1997; accepted 3 January 1998 maternal cells; we used polymerase chain reaction (PCR) amplification of highly polymorphic DNA regions (minisatellite sequences) to detect maternal DNA.
Materials and methodsPregnant women were recruited before delivery at Móstoles Hospital (Department of Obstetrics and Gynecology). Samples were collected after full-term vaginal delivery from women who had experienced no complications during pregnancy or at the time of delivery. Informed consent was obtained in all cases.
Collection of maternal and umbilical cord samplesCord blood was collected during the third stage of labor, before delivery of the placenta. Briefly, the umbilical cord was double-clamped and cut; after removal of the newborn, the umbilical vein of the cord was punctured aseptically and the blood was collected in a standard plastic blood donation bag containing CPD as anticoagulant. To minimize maternal cell contamination, we collected cord blood by gravity in a closed system, ...
We investigated whether 2-chlorodexoyadenosine could most cells are in the resting phase. 6,7 In vitro studies have excellently with the classical DNA fragmentation assays.12,13
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