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E Dickmeiss

Publications and source records attributed to E Dickmeiss.

At least 19 recordsLinked to original sources
PubMed2003

Pluripotent and myeloid-committed CD34+ subsets in hematopoietic stem cell allografts.

The present study compared the contents of pluripotent and lineage-committed hematopoietic progenitor cells (HPCs) in various types of allografts. Bone marrow (BM) allografts and single leukapheresis products (LPs) collected from G-CSF-mobilized donors contained similar amounts of pluripotent HPCs (CD34(+)CD38(-)) and total CD34(+) cells. However, the content of late-myeloid HPCs (CD34(+)CD33(+)CD15(+)) were significantly higher in BM grafts compared to LPs (P>0.02), whereas the contents of early-myeloid HPCs (CD34(+)CD33(+)CD15-) were 2.5-fold higher in LPs (P<0.03). In comparison to grafts from adult donors, cord blood (CB) grafts contained 26-65-fold lower amounts of early-myeloid HPCs (P<0.001), but only 8-12-fold lower contents of pluripotent HPCs (P<0.04). Additional findings demonstrated that among all tested parameters the numbers of early-myeloid HPCs were the most accurate measure of the total colony-forming cell (CFC) numbers in allografts. Hence, the earlier engraftment observed after transplantation of LPs compared to BM grafts might be explained by the higher content of early-myeloid HPCs/CFCs in LPs. Moreover, the slow engraftment following CB transplantation might not be affected essentially by the low number of myeloid HPCs, but rather by pluripotent HPCs. Finally, this study reports a new gating strategy for the enumeration of pluripotent CD34(+)CD38(-) subsets.

Antigens, CD↗
PubMed2003

Virological and immunological profiles among patients with undetectable viral load followed prospectively for 24 months.

OBJECTIVE: To quantify HIV-RNA in plasma, in lymphoid tissue and proviral DNA in peripheral blood mononuclear cells and to relate these to immunological markers among patients with plasma viral load counts of </= 200 HIV-RNA copies/mL. METHODS: A prospective study of one hundred and three patients was undertaken with an inclusion criteria of plasma viral load of </= 200 copies/mL. The patients had advanced HIV infection; 25% had developed AIDS. Patients were seen every 6 months for a period of 2 years. RESULTS: The median plasma viral load was < 20 copies/mL with no increase during follow-up. Thirty-one per cent had plasma viral load of </= 20 copies/mL at all visits, 44% had >/= 1 measurement with 21-200 and 25% had >/= 1 sample with plasma HIV-RNA > 200 copies/mL. Lymphoid tissue viral load was low at enrolment and declined further during follow-up. Baseline HIV-DNA and immunoglobulin (IgA) differed significantly between the plasma viral load rebound groups (P < 0.05). CONCLUSION: In this cohort, selected solely on the basis of having a plasma viral load of </= 200 copies/mL, we found stable or declining viral loads in the measured compartments during 2 years of follow-up. Baseline HIV-DNA and IgA levels were higher among patients with less complete virological suppression relative to patients with persistently undetectable plasma HIV-RNA. Hence, a high cellular level of HIV-DNA and high plasma IgA may predict subsequent development of low-grade viraemia.

Adult↗
PubMed2001

[Screening of donor blood for viral markers. Anti-HIV, HBsAg and anti-HTLV-I/II in Denmark 1990-1999].

INTRODUCTION: We describe the results of donor blood screening in Denmark for anti-HIV-1/2 in the period 1990-1999 and for anti-HCV, HBsAg, and anti-HTLV-I/II in the period 1994-1999. METHODS: Danish blood banks report the results of donor blood screening to the State Serum Institute on a monthly basis. This study concerns the data reported in the above two period. Reports from the years given above are worked out in the present study. RESULTS: The frequencies of infection among candidate donors are for HIV: 4.8 per 100,000; hepatitis C: 52.7 per 100,000; and hepatitis B: 60 per 100. The yearly incidences of new infections among the 260,000 regular donors in Denmark are for HIV: 0.42 per 100,000 regular donors; hepatitis C: 0.64 per 100,000 regular donors; and hepatitis B: 0.70 per 100,000 regular donors. All donations in Denmark were tested for anti-HTLV-I/II in the period 1 April 1994 to 1 October 1997, after which only candidate donors were tested. The frequency of HTLV-I infection in previously untested donors was 1 in 60,000 and that of HTLV-II infection 1 in 150,000. The frequency of HTLV-I infection among candidate donors was 1 in 50,000 and that of HTLV-II infection 1 in 100,000. No seroconverters have been found.

Adult↗
PubMed2001

[Risk of disease transmission via donor blood in Denmark at the turn of the century].

INTRODUCTION: Published results of donor blood screening in Denmark were used to calculate the risks of window phase donations. METHODS: The main parameter was the frequencies of a confirmed positive donation from regular donors per 100,000 donations are: 0.34, for HIV; 0.47 for hepatitis C virus; 0.53 for hepatitis B virus; and nil for HTLVI/II. The mean interdonation interval between donations from regular donors is six months year. Window phase duration were estimated to be 22 days for anti-HIV; 10 weeks for anti-HCV; and 56 days for HBsAg. Blood from candidate donors is not used in Denmark. Thus, the risk of a window phase donation equals the risk of a window phase donation in donations from regular donors. RESULTS: The risks of window phase donations in Denmark are: 1 in 2,000,000 for HIV; 1 in 500,000 for hepatitis C; 1 in 250,000 for hepatitis B; and immeasurably low for HTLVI/II. DISCUSSION: The measures taken nowadays to prevent infection from allogeneic blood transfusion have resulted in a risk reduction of HIV transmission by a factor 50 and of HCV transmission by a factor 400, compared with the risks prevailing in Denmark in the early 1980s. The present very low risk renders obsolete predeposited autologous blood solely on the indication to prevent infection. Zero risk of transmission of HIV and HCV might be approached by introducing NAT screening for these viruses.

Biomarkers↗
PubMed2001

Flow cytometric assessment of lymphocyte subsets, lymphoid progenitors, and hematopoietic stem cells in allogeneic stem cell grafts.

Currently, bone marrow (BM), cord blood (CB), and G-CSF-mobilized peripheral blood progenitor cells (PBPCs) are the most commonly used sources for allogeneic stem cell transplantation (SCT). The aim of this study was to assess the yields and distribution of lymphocyte subsets, lymphocyte progenitors and hematopoietic stem cells (HSC) in each type of allograft by three-color flow cytometry. The yields of CD34(+)CD38(-) HSCs did not differ significantly between BM grafts (2.80 +/- 0.74 x 10(6)) and leukapheresis products (LPs) (1.82 +/- 0.64 x 10(6)), and were lowest in CB grafts (0.21 +/- 0.05 x 10(6)). For most lymphocyte subsets yields were lowest in CB grafts and significantly higher in LPs than in BM grafts. BM grafts, however, contained the highest yields of CD34(+)CD19(+)CD20(-) B cell progenitors and CD19(+)CD20(-) B cells. The relative frequencies of the naive CD45RA(+)CD45RO(-) phenotype among CD4(+) and CD8(high) T cells were highest in CB grafts (P < or = 0.001), and higher in LPs than in BM grafts (P < or = 0.02). The latter finding was in accordance with a preferential G-CSF mobilization of naive T cells relative to the total lymphocyte population (P < or = 0.014). CD3(+)CD8(low) and CD3(+)CD8(low)CD4(-) subsets, which facilitate engraftment in murine transplantation models, demonstrated a tendency towards lower frequencies among T cells in CB grafts and LPs compared to BM grafts. This observation coincided with a significantly reduced mobilization of subsets potentially enriched for facilitating cells as compared to the total lymphocyte population (P < or = 0.036). The CD34(+) compartment of CB grafts contained a significantly higher percentage (12.1%) of CD34(+)CD7(+)CD3(-) T cell progenitors than those of BM grafts (5.1%) and LPs (3.6%). In addition, CB lymphocytes contained the highest fraction of CD3(-)CD16/56(+) NK cells (P < or = 0.013) and almost no CD3(+)CD16/56(+) NKT cells (P < 0.001) compared to adult cell sources. In summary, LPs, CB allografts and BM allografts differ widely with respect to the cellular composition of their lymphocyte compartments, which is partially affected by a varying mobilization efficiency of G-CSF for distinct lymphocyte subsets.

Adult↗
PubMed2001

Recruitment of CD34+ cells during large-volume leukapheresis.

Mobilized peripheral blood stem and progenitor cells (PBPCs) are increasingly used to restore hematopoiesis after myeloablative treatment. To obtain a sufficient number of CD34(+) cells, many studies have focused on the improvement of the collection technique during the leukapheresis procedure (LP), and so-called large-volume leukapheresis (LVL) procedures have been developed. Such procedures can be performed by extending the duration of the LP and/or by increasing the inlet flow rate. However, no previous studies have compared the efficiency of these procedures. In the present study, we compared the kinetics of PBPCs recruitment (including CD34(+) cell subsets), the PBPCs yield, and the collection efficiency as well as the overall feasibility of the procedures during a single LVL performed by standard (group I) (median 85 ml/min; range 50-97 ml/min) and high inlet flow rates (group II) (median 130 ml/min; range 110-150 ml/min). Seven patients with hematological malignancies were enrolled and allocated to each group. The patients' blood volumes (BV) were processed four times. The apheresis product (AP) was collected in four separate bags, which were changed every time one BV had been processed. The CD34(+) cell number and CD34(+) cell subsets were assessed in the four collection bags and in peripheral blood (PB) before every time one BV had been processed and after the leukapheresis. The CD34(+) cell yield exceeded the pre-apheresis CD34(+) cell number per ml BV in 6 out of 7 patients in group I and in 3 out of 7 patients in group II. In group II, the recruitment of CD34(+) cells from the bone marrow (BM) to PB starts in the second collection period--as early as 30-60 min after initiating the procedure. No exhaustion in the recruitment was observed in the two groups for at least 5 h during the leukapheresis, and all CD34(+) cell subsets were recruited at a steady rate. However, the collection efficiency in group II was only half of that in group I. In addition, we experienced many technical problems during the leukapheresis in group II. Thus, in 4 out of 7 patients in this group, it was not possible to perform the maximal inlet flow rate because of catheter problems. In conclusion, due to the technical problems associated with the high inlet flow rate procedure and the fact that the relative number of CD34(+) cells harvested and recruited during the leukapheresis was higher in group I than II and, also reflected an approximately two-fold higher collection efficiency, we recommend that LVL be performed by standard inlet flow rate.

Adult↗
PubMed1999

Single leukapheresis products collected from healthy donors after the administration of granulocyte colony-stimulating factor contain ten-fold higher numbers of long-term reconstituting hematopoietic progenitor cells than conventional bone marrow allografts.

Cytokine-mobilized peripheral blood progenitor cells (PBPCs) have been used successfully for hematopoietic reconstitution following allogeneic transplantation. The ease of harvest, the faster engraftment and the high yield of CD34+ cells have made this source of hematopoietic progenitor cells (HPCs) an attractive alternative to bone marrow (BM). In the present study we compared the engraftment potential of conventional BM allografts and single leukapheresis products (LPs) collected from healthy donors following the administration of granulocyte colony-stimulating factor (G-CSF). For this, lineage-committed and primitive HPCs were assessed by flow cytometry and by colony- and cobblestone area-forming cell (CFC, CAFC) assays. Mean numbers of CD34+ cells in LPs (n = 11) were similar to that of BM grafts (n = 12) (278+/-57 vs 227+/-34 x 10(6) CD34+ cells). The frequencies of CFCs, week 5 CAFCs and week 8 CAFCs were 1.6-, 8.4- and 10.3-fold higher in the CD34+ compartment of mobilized blood than that of marrow, resulting in significantly higher yields of clonogenic HPCs in LPs when compared to BM grafts. We conclude that G-CSF preferentially mobilizes clonogenic progenitors capable of short- and, in particular, longterm reconstitution, and that the engraftment potential of single LPs is superior to that of BM allografts. Hence, the use of PBPCs may be favorable for protocols that include graft manipulations with expected cell loss (eg T cell depletion, CD34+ selection). PBPCs may also be advantageous for gene therapy trials due to their high numbers of potential target cells (eg CAFCs).

Adolescent↗
PubMed1999

A comparative study of CD34+ cells, CD34+ subsets, colony forming cells and cobblestone area forming cells in cord blood and bone marrow allografts.

Cord blood (CB) has become an alternative source of hematopoietic progenitor cells (HPCs) for allogeneic transplantation. We have developed a new efficient protocol for CB collection. Using this method an average of 17.7 x 10(8) [range (6.8-29.6) x 10(8), n = 13] total nucleated cells (TNCs) were harvested. Based on recent Eurocord data, which have shown safe engraftment using a threshold dose of 0.37 x 10(8) CB TNCs/kg body weight (BW), we calculated that six out of thirteen CB grafts collected by this method were sufficient to engraft adults. The CB derived CD34+ population contained two-fold higher numbers of committed HPCs (CFU-GM, BFU-E) and six-fold higher numbers of pluripotent HPCs [CD34+/CD38- cells, wk 5 and wk 8 cobblestone area forming cells (CAFCs)] than the CD34+ population of BM. Extrapolation revealed that BM grafts providing the threshold dose for allogeneic transplantation of 2 x 10(8) TNCs/kg BW contained nearly 3 times more pluripotent HPCs than CB grafts providing the Eurocord threshold dose. The assessment of CD34+/CD38(-) cell numbers in CB grafts was highly reproducible and correlated well with the in vitro performance of pluripotent HPCs, i.e. numbers of CAFCs. We conclude that CB grafts providing high numbers of TNCs have the potential to engraft adults and that the enumeration of pluripotent HPCs by flow cytometry may be a useful tool to define the ultimate threshold dose for CB transplantation.

ADP-ribosyl Cyclase↗
PubMed1998

BEAM+autologous stem cell transplantation in malignant lymphoma: 100 consecutive transplants in a single centre. Efficacy, toxicity and engraftment in relation to stem-cell source and previous treatment.

One hundred consecutive patients with malignant lymphoma treated with high-dose chemotherapy and autologous stem cell transplantation, followed at least 1 yr post-transplant, are reported, 68 with non-Hodgkin's lymphoma and 32 with Hodgkin's disease. At transplant, 23 patients were in first remission, 69 in later chemosensitive disease and 8 were chemotherapy resistant. Based on previous treatment and stem-cell source, the patients were subdivided into 3 cohorts: BMT1: bone-marrow harvest and transplant after > or =3 treatment regimens (38 patients); BMT2: bone marrow harvest and transplant after less than 3 treatment regimens (24 patients); PBSCT: peripheral-blood stem cell transplant (38 patients, 5 of these with CD34+ cell selected PBSC). The 4-yr survival and progression-free survival of all patients was 45 and 40%, respectively. Forty-one patients have died, 27 of lymphoma, evenly distributed in the cohorts. Fourteen treatment-related deaths occurred, 13 of these in the BMT1 cohort, significantly more than in the other cohorts (p=0.001). In univariate survival analysis cohort, age, disease status at transplant and number of previous treatment regimens were significant. In multivariate survival analysis cohort, age and sex were independently significant, women having a shorter survival. The patients transplanted with unselected PBSC had significantly shorter duration of pancytopenia and hospital stay than the otherwise comparable BMT2 patients, but their progression-free survival was identical. We confirm that high-dose therapy with autologous stem cell transplant from blood or bone marrow in not-too-heavily pretreated patients is a safe procedure but will cure only half the patients.

Adult↗
PubMed1998

Immunephenotyping of T lymphocytes from patients after allogeneic bone marrow transplantation.

The relative distribution of T cell subsets as defined by MABs was analyzed in PBMCs from 56 patients with various hematologic diseases. The percentage of PBMCs expressing the CD5 antigen revealed normal values shortly after transplantation. In most patients lymphocytes expressing CD8 were found in high proportion and CD4 in a low percentage. This resulted in a low CD4/CD8 ratio compared with that of lymphocytes from normal controls. In the course of time, a trend toward normalization was observed for all parameters investigated, however the kinetics of the recovery showed a marked heterogeneity. Nevertheless, we found a statistical correlation between the CD4+ cell count and the PHA transformation response. This could however, not be shown in ConA and PWM stimulated proliferation. No other correlation was found between any lymphocyte phenotype, as defined by MABs, and proliferative responses in vitro.

Bone Marrow Transplantation↗
PubMed1997

Heterozygosity for a deletion in the CKR-5 gene leads to prolonged AIDS-free survival and slower CD4 T-cell decline in a cohort of HIV-seropositive individuals.

OBJECTIVE: Recently, it has been shown that a homozygous 32 base-pair deletion in the gene encoding CKR-5, a major coreceptor for HIV-1, leads to resistance to infection with HIV-1. We have investigated whether HIV-seropositive individuals who were heterozygous for the CKR-5 deletion had a different course of the disease. DESIGN: Thirty-five high-risk HIV-seronegative and 99 HIV-seropositive Danish homosexual men followed form 1985 to 1996 and 37 blood donors were analysed for their CKR-5 genotype by polymerase chain reaction. RESULTS: Two (6%) of the 35 HIV-seropositive subjects at high-risk of infection were homozygous and seven (20%) were heterozygous for the CKR-5 deletion. This was not significantly different from the distribution in normal donors. Twenty-two (22%) of the 99 HIV-seropositive subjects were heterozygous and none was homozygous. Two subgroups of patients who had an opposite course of the HIV disease were identified. Of nine long-term non-progressors, six (66%) were heterozygous for the deletion. This frequency is significantly higher than in nine rapid progressors of whom non was heterozygous. The frequency of heterozygotes in long-term non-progressors was also significantly higher than in the cohort as a whole. A Kaplan-Meier plot of the HIV-seropositive subjects, of whom 57 developed AIDS, showed a significantly better prognosis within the first 7 years of follow-up for those who were heterozygous for the deletion. Heterozygous individuals also had a significantly slower decrease in CD4 T-cell count per year. CONCLUSION: Individuals who are heterozygous for the 32-base-pair deletion in the CKR-5 gene have a slower decrease in their CD4 T-cell count and a longer AIDS-free survival than individuals with the wild-type gene for up to 11 years of follow-up.

CD4 Lymphocyte Count↗