Biomedical subjects

Ebbe Dickmeiss

Publications and source records attributed to Ebbe Dickmeiss.

14 recordsLinked to original sources

PubMed2006

[Antenatal determination of fetal RhD-blood type based on fetal DNA in plasma from the RhD-negative mother--secondary publication].

We present a reliable test for prenatal prediction of fetal RhD type using maternal plasma from RhD-women. This test is needed for a future antenatal RH prophylaxis. A new real time PCR based assay targeting RHD exon 7 and a published assay for RHD exon 10 were used to determine the fetal RHD status in DNA extracted from plasma from 56 pregnant women in 15th-36th week of gestation. Prediction of fetal RhD type was compared with the phenotype determined after birth, and showed 100% concordance. This setup will be of value in antenatal RH prophylaxis and in the management of immunised women.

DNA↗

PubMed2006

Cytokine gene expression in peripheral blood mononuclear cells and alloreactivity in hematopoietic cell transplantation with nonmyeloablative conditioning.

Cytokines are thought to play an important role in the pathophysiology of graft-versus-host disease (GVHD). To study the relationship between cytokines and GVHD, we obtained peripheral blood mononuclear cells (MNCs) from 21 patients with hematologic malignancies and their HLA-identical sibling donors before and sequentially after hematopoietic cell transplantation (HCT) with nonmyeloablative conditioning. The MNCs were cultured for 72 hours either alone or in mixed lymphocyte cultures with irradiated MNCs of recipient, donor, or HLA-mismatched third-party origin. The gene expression of interleukin (IL)-2, IL-4, IL-10, IL-18, tumor necrosis factor alpha, and transforming growth factor beta in each culture was then measured by real-time quantitative reverse transcriptase-polymerase chain reaction. The composition of the responder MNCs differed between patients and donors and changed after HCT, with a possible influence on the results. Early after transplantation (day +14), the IL-10 messenger RNA (mRNA) level in response to recipient or donor antigens was higher in patients who did not develop clinically significant acute GVHD when compared with the level in patients who subsequently developed acute GVHD grades II to IV (P = .005 and P = .004, respectively). The IL-10 mRNA level on day +14 was highly correlated with the pretransplantation mRNA level of the recipient MNCs but not with the level of the donor MNCs; this suggests that the IL-10 mRNA detected on day +14 originated from responder cells of recipient origin. A higher IL-10 mRNA level was found in MNCs obtained before transplantation from recipients whose disease progressed or relapsed after the transplantation when compared with the level in patients whose disease did not progress or relapse (P = .03). In conclusion, a high IL-10 gene expression in the recipient MNCs may be related to a reduced incidence of acute GVHD grades II to IV and a reduced graft-versus-tumor effect after HCT with nonmyeloablative conditioning.

Adult↗

PubMed2005

Limiting dilution analysis of interleukin-2 producing helper T-cell frequencies as a tool in allogeneic hematopoietic cell transplantation.

BACKGROUND: A reliable in vitro test that estimates the level of ongoing alloreactivity would be valuable in allogeneic hematopoietic cell transplantation (HCT) as a help to guide clinical interventions such as donor lymphocyte infusions and changes in the immunosuppression. In the present study, the use of limiting dilution analysis of interleukin-2 (IL-2) producing helper T lymphocyte frequencies (HTL assay) as a way to quantify alloreactivity following HCT was investigated. METHODS: Serial HTL assays were performed following allogeneic HCT with myeloablative or nonmyeloablative conditioning in 26 patients with hematologic malignancies. RESULTS: Deviations from single-hit kinetics were frequently observed in the HTL assays and a nonlinear model was therefore used for analysis. The results of this analysis suggested the presence of an inhibitory cell population. Inhibition was observed in the majority of patients and was not restricted to a specific transplant regimen. Inhibition occurred more often with high frequencies of IL-2 producing cells, indicating a physiological role of the putative inhibitory cell population in the regulation of an immune response. Higher frequencies of IL-2 producing cells were observed in patients with acute graft-versus-host disease grades II-IV than in patients with grades 0-I (P = 0.046), indicating that the degree of ongoing alloreactivity is indeed quantified by the HTL assay. CONCLUSIONS: We find that the HTL assay may yield interesting insight into regulation of immune responses following allogeneic HCT, but because of the complexity of the results obtained, its use as a routine procedure to guide immunosuppression cannot be recommended.

Bone Marrow Transplantation↗

PubMed2005

Reliable test for prenatal prediction of fetal RhD type using maternal plasma from RhD negative women.

OBJECTIVES: The objective of this study was to establish a reliable test for prenatal prediction of fetal RhD type using maternal plasma from RhD negative women. This test is needed for future prenatal Rh prophylaxis. METHODS: A novel real-time PCR-based assay targeting RHD exon 7 combined with a published assay for RHD exon 10 were used to determine the fetal RHD status in DNA extracted from plasma, sampled from 56 pregnant RhD negative women in 15th-36th week of gestation. Thirty-eight samples were from ongoing pregnancies of Danish women and 21 samples from 18 pregnant women were stored anonymized samples from the International Blood Group Reference Laboratory, Bristol, United Kingdom. Prediction of fetal RhD type was compared with the serological result obtained after birth. RESULTS: The prediction of the fetal RhD type was in 100% concordance with the serological RhD type from the 16th week of gestation. One sample from the 15th week of gestation was inconclusive. The number of copies of fetal RHD DNA was found to increase with gestational age. Low levels of DNA were found to follow the Poisson distribution (p = 1.0000). CONCLUSION: Our set-up was very reliable for determination of fetal RhD genotype, and thus will be of value in prenatal Rh prophylaxis and in the management of immunized women.

DNA↗

PubMed2005

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.

Bacteria↗

PubMed2004

Chimerism studies in HLA-identical nonmyeloablative hematopoietic stem cell transplantation point to the donor CD8(+) T-cell count on day + 14 as a predictor of acute graft-versus-host disease.

Chimerism analysis of hematopoietic cells has emerged as an essential tool in nonmyeloablative hematopoietic stem cell transplantation. We have investigated the development of donor chimerism in granulocytes and CD4(+) and CD8(+) T cells in blood and bone marrow of 24 patients with hematologic malignancies who received HLA-identical sibling peripheral blood stem cell grafts after conditioning with fludarabine and 2 Gy of total body irradiation. The T-cell chimerism of blood and bone marrow was tightly correlated. Complete donor chimerism was reached earlier in the granulocytes than in the T cells. Mixed T-cell chimerism was common at the time of onset of acute graft-versus-host disease (aGVHD), and both CD4(+) and CD8(+) donor T-cell chimerism increased with the occurrence of aGVHD grades II to IV (P =.0002 and P =.019, respectively). The rate of disappearance of recipient CD8(+) T cells was faster in patients with aGVHD grades II to IV than in patients without clinically significant aGVHD (P =.016). This observation indicates a role of graft-versus-lymphohematopoietic tissue reactions in creating complete donor T-cell chimerism. A donor CD8(+) T-cell count above the median on day +14 increased the risk of subsequent development of aGVHD grades II to IV (P =.003).

Acute Disease↗

PubMed2004

Haematopoietic stem cell transplantation with non-myeloablative conditioning in the outpatient setting: results, complications and admission requirements in a single institution.

Thirty patients with haematological malignancies received peripheral blood stem cells from human leucocyte antigen (HLA)-identical sibling donors after non-myeloablative conditioning with fludarabine and total body irradiation. Twenty-seven patients received the transplant as an outpatient procedure. All patients engrafted. The probability of acute graft-versus-host disease (GVHD) grades II-IV and extensive chronic GVHD was 57% and 80%, respectively. Patients alive on day +365 experienced a median of 44 d (range 4-151) of hospitalization during the first year. In the entire cohort, GVHD accounted for 22%, infections for 18%, thrombotic thrombocytopenic purpura (TTP) for 16% and engraftment syndrome for 14% of the time in hospital. The 1-year risk of TTP was 26%. Acute GVHD was a risk factor for the development of TTP (P = 0.008). With a median follow-up of 602 d, the 2-year estimates for overall survival, progression-free survival, non-relapse mortality and relapse related mortality were 68%, 43%, 22% and 13%, respectively. This transplantation regimen is feasible and induces long-term remissions in heavily pretreated patients. The procedure can be performed in the outpatient setting, but complications could result in a substantial number of admissions during the first year.

Adult↗

PubMed2003