PubMed Health⌕ Search

Biomedical subjects

P Höcker

Publications and source records attributed to P Höcker.

At least 37 records · Page 2Linked to original sources
PubMed2001

Platelet-reactive HLA antibodies associated with low posttransfusion platelet increments:a comparison between the monoclonal antibody-specific immobilization of platelet antigens assay and the lymphocytotoxicity test.

BACKGROUND: Platelet-reactive HLA antibodies are a major reason for low posttransfusion platelet increments. The clinical importance and value of the test systems for their in vitro determination is still controversial. STUDY DESIGN AND METHODS: A prospective analysis of HLA antibodies was performed in sera obtained once a week for at least 4 consecutive weeks from 55 patients (female/male, 28/27; age: median, 49 years; range, 18-69) undergoing intensive chemotherapy and in need of prophylactic platelet transfusions. All sera (n = 330) were analyzed by the monoclonal antibody-specific immobilization of platelet antigens (MAIPA) assay and by the standard lymphocytotoxicity test (LCT). RESULTS: In the MAIPA, 24.5 percent of sera (81/330) obtained from 22 patients contained HLA antibodies. These were detected significantly more often by the MAIPA assay than by the LCT (24.5% vs. 8.2%). Fifty-five sera (20 patients) were positive in the MAIPA assay only. In 15 patients, HLA antibodies were transient. In 3 patients, HLA antibodies were detected earlier by the MAIPA assay than by the LCT. Significantly more sera obtained at the time of low posttransfusion platelet increments were positive in MAIPA alone, rather than in both MAIPA and the LCT (44% vs. 17%). CONCLUSION: The MAIPA assay is more sensitive than the standard LCT in detecting platelet-reactive HLA antibodies. These MAIPA-positive/LCT-negative HLA antibodies affect the posttransfusion platelet increment.

Adolescent↗
PubMed2001

Increased serum flt3-ligand in healthy donors undergoing granulocyte colony-stimulating factor-induced peripheral stem cell mobilization.

The effect of granulocyte colony-stimulating factor (G-CSF) induced mobilization of peripheral blood progenitor cells (PBPC) on the endogenous serum levels of cytokines stem cell factor (SCF) and flt3-ligand (flt3-L) was studied in 18 healthy subjects undergoing allogeneic PBPC donation. Donors received a standardized mobilization regime consisting of a 4-day course of G-CSF, with leukapheresis on day 5. Endogenous serum flt3-L and SCF were determined prior to G-CSF administration, on the day of leukapheresis, and followed up until day +100 after cessation of G-CSF administration. The administration of G-CSF resulted in a transient elevation of endogenous flt3-L serum levels. At the day of leukapheresis serum flt3-L showed a median increase of 75% compared to serum flt3-L levels obtained before G-CSF treatment. The increase in serum flt3-L levels showed no correlation with the total number of progenitor cells mobilized. Cessation of G-CSF treatment led to normalization of serum flt3-L within 7 days post G-CSF administration. In contrast, serum CSF levels remained unchanged in response to G-CSF administration. Our results demonstrate a transient surge in serum flt3-L in relation to G-CSF-induced PBPC mobilization, although the assessment of endogenous flt3-L give no information regarding the ability for G-CSF-induced PBPC recruitment in healthy individuals.

Adolescent↗
PubMed2000

Excellent disease eradication by myeloablative therapy and stem-cell transplantation in patients with acute myelogenous leukemia.

Between February 1982 and 1999, 118 consecutive patients (65 male, 53 female) with acute myelogenous leukemia (AML), with a median age of 35 years (range 17-56 years), received stem-cell grafts from a human leukocyte antigen-identical sibling (n = 71), one-antigen-mismatched family member (n=2), matched unrelated donor (n=15), one-antigen-mismatched unrelated donor (n = 4) or an autologous (n = 26) graft. At the time of transplant, 56 patients were in the first complete remission (CR), 27 in the second CR, 6 in untreated relapse, 17 in primary refractory, and 12 in refractory relapse. The French-American-British classification (FAB) subtypes were as follows: M1 (n=25), M2 (n=28), M3 (n=11), M4 (n =32), M5 (n=16), M6 (n = 6). For conditioning, most patients underwent total body irradiation-containing regimens. As of 28 February, 1999, probability of leukemia-free survival (LFS) is 58% for patients after related and 45% after unrelated stem-cell transplantation (SCT). The probability of LFS is 70% for patients given allogeneic transplants in the first CR compared with 33% for those beyond the first CR at SCT. In autologous stem-cell graft recipients, the probability of LFS is 37%. Transplant-related mortality was 28% after related, 20% after unrelated, and 4% after autologous SCT. Probability of relapse for patients given related-donor stem-cell grafts in the first CR and beyond the first CR is 30% and 67%, 55% after unrelated and 63% after autologous stem-cell grafting. Thus, myeloablative therapy followed by allogeneic stem-cell infusion has a high curative potential for patients with AML in remission and offers substantial benefits to patients in advanced disease.

Adolescent↗
PubMed2000

Permanent tunneled silicone central venous catheters for autologous PBPC harvest in children and young adults.

Children with high risk malignancies are usually given permanent (Hickman-type) tunneled silicone rubber central venous catheters (silicone CVCs) for the administration of chemotherapy. In the past, these children received an additional short-term polyurethane dialysis CVC for stem cell apheresis. To avoid placement of an additional short-term CVC, we started in 1995 to use pre-existing silicone CVCs for PBPC harvests. From May 1996 to February 1999 we evaluated 165 harvests in 37 children and 14 young adults (16-28 years) treated with high-dose chemotherapy and stem cell support, comparing CD34+ cell harvest efficiency, catheter tolerability, and complications in three different approaches to vascular access. Pre-existing silicone CVCs (64%) or peripheral venous cannulae (15%) were the first choice for venous access. Only when these failed were polyurethane CVCs (21%) used. No significant difference was seen between these three groups, even after dividing the silicone CVC group (105 harvests in 32 patients) into three subgroups according to weight and age. The most frequent problems were citrate toxicity (n = 33), mechanical obstruction inside (n = 9) and outside the cell separator (n = 2), decreased draw line flow in silicone CVCs (n = 7), decreased draw line flow in peripheral venous cannulae (n = 6), and one occlusion in a polyurethane CVC. Pre-existing CVCs and peripheral venous cannulae functioned efficiently when used as a draw line in 79% of the apheresis procedures without significantly reducing single harvest efficiency or catheter tolerability. Consequently, the risks and costs associated with the placement of a dialysis CVC could be avoided in the majority of cases. Bone Marrow Transplantation (2000) 26, 781-786.

Adolescent↗
PubMed2000

Regeneration of erythropoiesis after related- and unrelated-donor BMT or peripheral blood HPC transplantation: a major ABO mismatch means problems.

BACKGROUND: Blood group incompatibility in allogeneic BMT is common but does not appear to affect the outcome in terms of incidence of graft rejection or delayed engraftment. However, major ABO incompatibility may be associated with prolonged erythroid aplasia. STUDY DESIGN AND METHODS: In a retrospective analysis of 286 allogeneic transplant recipients, the prevalence of prolonged erythroid aplasia, including pure RBC aplasia, was determined. RESULTS: Patients receiving major ABO-incompatible grafts showed a significant delay in reticulocyte engraftment (median, 32 days; range, 12-347) from that in patients receiving ABO-identical (20; 10-152) or minor ABO-incompatible (21; 12-47) grafts. Pure RBC aplasia occurred in 7 (3%) of 240 evaluable recipients and was observed only in the major ABO-incompatible group (7/43, 16%). Treatment of pure RBC aplasia consisted of either plasma exchange, which resulted in a response within 16 to 68 days, or immunoadsorption, in which the response occurred between Days 119 and 204 after initiation of treatment. CONCLUSION: Major ABO incompatibility may lead to delayed reticulocyte engraftment, resulting in prolonged transfusion dependency and increased risks of transmission of infection and iron overload. Therefore, therapeutic strategies should be taken into consideration to allow erythroid reconstitution in these patients.

ABO Blood-Group System↗
PubMed2000

A cell-kinetic model of CD34+ cell mobilization and harvest: development of a predictive algorithm for CD34+ cell yield in PBPC collections.

BACKGROUND: Mobilization and homing of PBPCs are still poorly understood. Thus, a sufficient algorithm for the prediction of PBPC yield in apheresis procedures does not yet exist. STUDY DESIGN AND METHODS: The decline of CD34+ cells in the peripheral blood during apheresis and their simultaneous increase in the collection bag were determined in a prospective study of 18 consecutive apheresis procedures. A cell-kinetic, four-compartment model describing these changes was developed. Retrospective data from 136 apheresis procedures served to further improve this model. A predictive algorithm for the yield was developed that considered the sex, weight, and height of the patient, the number of CD34+ cells in peripheral blood before apheresis, the inlet flow, and the duration of the apheresis. The accuracy of this algorithm was evaluated by comparison of the predicted and the observed yields of CD34+ cells in 105 prospective autologous and 148 retrospective allogeneic apheresis procedures. RESULTS: The correlation between predicted and observed yields was good for the autologous and allogeneic groups with a correlation coefficient (r) of 0.8979 and 0.8311 (p<0.0001), respectively. The regression is described by the equations log (measured value [m]) = 1.0118 + 0.8595 x log (predicted value [p]) for the autologous and log (m) = 2.226 + 0.7559 x log (p) for the allogeneic group. The respective equations for the zero-point regression are log (m) = 1.014 x log (p) and log (m) = 1.026 x log (p). The probability that the measured value was 90 percent or more of the predicted value was 83.8 percent for the autologous and 90.5 percent for the allogeneic apheresis procedures. CONCLUSION: The predictive accuracy of the algorithm and the slope of the zero-point regression curve were higher for allogeneic than autologous PBPC collections. The predictive algorithm may be a useful tool in PBPC harvest, enabling the adaptation of the size of the apheresis to the needs of each patient.

Algorithms↗
PubMed1999

The rise of reticulated platelets after intensive chemotherapy for AML reduces the need for platelet transfusions.

We assumed that a recovery of thrombopoiesis after intensive chemotherapy for acute myelogenous leukemia (AML) could reduce the need for prophylactic platelet transfusions. We therefore assessed the start of platelet production by means of daily determination of reticulated platelets (RP). The increase in RP occurred on day 20 (median) after the start of chemotherapy and was followed by a rise of peripheral platelet counts 2-3 days thereafter. Consequently, a rise of RP during the period of recovery can be regarded as representing the reconstitution of the peripheral platelet count and may reduce or eliminate the need for prophylactic platelet transfusions.

Adult↗
PubMed1999

Low incidence of molecular evidence for tumour in PBPC harvests from patients with high risk Ewing tumours.

Reverse transcriptase polymerase chain reaction (RT-PCR) was applied to evaluate the frequency of tumour cells in PBPC products from 15 high risk Ewing tumour (ET) patients who were treated according to EICESS 92 with high-dose chemotherapy (HDC) and stem cell rescue. Initial tumour cell contamination of the bone marrow (BM) detected by light microscopy was found in five and by RT-PCR in eight cases. RT-PCR was performed on each PBPC sample repeatedly at a sensitivity comparable to 20-100 highly EWS-Fli1 expressing tumour cells per 10 ml of fresh blood. Irrespective of the extent of BM involvement at diagnosis, all BM samples obtained before harvest were RT-PCR negative. Among 12 of 35 analysed apheresis products with single positive RT-PCR results only one sample tested reproducibly positive for tumour cell contamination in independent determinations. These preliminary data suggest that tumour cell contamination of PBPC is rarely found in patients with ET.

Adolescent↗
PubMed1999

Transplantation of highly purified peripheral blood CD34+ cells from HLA-mismatched parental donors in 14 children: evaluation of early monitoring of engraftment.

HLA-mismatched family members may represent an important cell source for patients that require stem cell transplantation but lack both a matched sibling donor and a closely matched unrelated donor. We report the outcome of 19 transplantations from HLA two- or three- loci mismatched parental donors in which 14 pediatric patients with hematological malignancies or other disorders, received a median of 21.5 x 106 (range, 5.4-58) highly purified CD34+peripheral blood stem cells (PBSC), as well as 4.7 x 104 (range, 0.4-12) donor T cells per kg body weight. T cell depletion was performed using a two-step CD34-positive selection on two different magnetic beads devices. Ten of 14 patients presented with rapid myeloid engraftment. The four patients who presented with graft failure (two non-engraftments, two rejections) received a second stem cell graft and one a third. Graft rejection was detected early by polymerase chain reaction (PCR) analysis of FACS-sorted T cells. Eight of the 14 patients are still alive after a median observation period of 15. 6 months (range, 3-31.3) with full donor chimerism in all hematopoietic cell lineages. No acute organ graft-versus-host disease (GVHD) and no chronic GVHD have occurred. One patient experienced relapse of leukemia. We conclude that transplantation of allogeneic PBSC from haploidentical donors will open new perspectives for pediatric patients for whom an HLA-matched stem cell graft is not available. Close monitoring of recipient and donor hematopoiesis might be of clinical value, to recognize early engraftment or rejection.

Adolescent↗
PubMed1999

Leucocyte transfusions from rhG-CSF or prednisolone stimulated donors for treatment of severe infections in immunocompromised neutropenic patients.

Sepsis in profound neutropenia after chemotherapy is associated with high mortality despite appropriate antibacterial or antifungal treatment. In a prospective phase I/II study we evaluated the feasability and efficacy of leucocyte transfusions (LT) in patients with malignancies or haematological disorders who were suffering from severe bacterial or fungal infection during therapy-related bone marrow aplasia. 30 patients with severe neutropenia and clinical signs of life-threatening sepsis not responding to adequate treatment, received LT from rhG-CSF-stimulated family donors or from prednisolone-primed volunteers. A total of 301 LT were administered. The median number of LT per patient was seven (range three to 65), the median duration of LT treatment was 8 d (range 2-35). The white cell count (WBC), absolute neutrophil count (ANC) and lymphocyte count of the concentrates from rhG-CSF-stimulated donors were significantly higher than those from prednisolone-primed volunteers (P = 0.0001). Despite the critical condition of the patients, LT were generally well tolerated. Only 39 (12.9%) LT were associated with adverse reactions. The transfusion of leucocytes collected by continuous flow leukapheresis from both rhG-CSF and prednisolone stimulated donors resulted in a measurable increment of the peripheral leucocyte and ANC counts in our patients. On day 100 after the first LT, 20/30 patients were alive with complete clearance of the infection.

Adolescent↗
PubMed1999

Safety issues of plateletpheresis: comparison of the effects of two cell separators on the activation of coagulation, fibrinolysis, and neutrophils and on the formation of neutrophil-platelet aggregates.

BACKGROUND: Although many donors undergo repeated plateletpheresis, data on the consequences of plateletpheresis for the donor's health remain scarce. Thus, the effect of plateletpheresis on the activation of coagulation, fibrinolysis, and neutrophils was investigated. STUDY DESIGN AND METHODS: Part 1: Sixteen healthy men were randomly assigned to undergo plateletpheresis on a cell separator (AMICUS, Fenwal Baxter; or MCS 3p, Haemonetics). The effects of plateletpheresis on plasma levels of prothrombin fragment (F(1+2)), D-dimer, plasmin-plasmin inhibitor (PPI) complexes, and plasminogen activator inhibitor (PAI-1); on the activation of neutrophils (% L-selectin+); and on the frequency of platelet-neutrophil aggregates (% CD41+ neutrophils) were compared. Part 2: Ten healthy men received infusions of ACD-A and placebo without apheresis in a randomized, double-blind crossover study to control for the pharmacologic effects of citrate. RESULTS: Part 1: No change in F(1+2) occurred (p>0.05), which indicated that plateletpheresis did not enhance coagulation. Levels of D-dimer, PPI, and PAI-1 decreased over time on the AMICUS (p<0.001). Plateletpheresis did not activate neutrophils (p>0.05), but it decreased the percentage of CD41+ neutrophils (p<0.003). An approximately 80-percent drop in mononuclear cells was observed in the extracorporeal circulation of the AMICUS (p<0.001 vs. baseline and p = 0.005 vs. MCS 3p), and circulating lymphocyte and monocyte counts decreased concomitantly. Part 2: Infusion of ACD-A slightly decreased D-dimer levels (p<0.05), and both infusions decreased the circulating lymphocyte counts. CONCLUSION: Plateletpheresis can be regarded as safe with respect to the activation of coagulation or neutrophils. The consequences for the donor's health of the decrease in D-dimer, PPI, and PAI-1 may deserve further investigation.

Adult↗
PubMed1999

The proportion of reticulated platelets is higher in bone marrow than in peripheral blood in haematological patients.

Since the detection that platelets originate from megakaryocytes (MK), the site of megakaryocyte fragmentation has been disputed. Some authors have even postulated that platelets are solely produced in the lungs. Thus, we have directly measured platelet generation in the bone marrow (BM) by comparing the relative number of young RNA-containing, so-called reticulated platelets (%RP) in the BM and in the peripheral blood (PB). Two separate prospective, cross sectional trials have been conducted in patients routinely undergoing BM biopsies for diagnostic purposes. In the first part of the study 30 patients with stem cell or bone marrow transplantation were examined. The second part of the study was performed in 62 haematological patients visiting the outpatient's clinic. Median %RP were higher in BM than in PB (p <0.001). In the second part of the study the difference averaged 133% (interquartile range: 30-383%). There was a moderate correlation between %RP in BM and in PB (r = 0.67; p <0.001). The absolute number of RP in PB correlated weakly with the number of megakaryocytes (0.42; p = 0.001), which was due to a correlation between the platelet counts and the megakaryocyte counts (r = 0.55; p <0.001 in biopsies). Two patients with autoimmune antibodies against GPIIb/IIIa exhibited 10% and 16% RP in PB, and had 29% and 59% RP in BM, respectively. It is concluded that the relative number of RP is significantly higher in BM than in blood. This supports the notion that platelets are at least in part released from MK in the bone marrow, particularly in patients suffering from immune thrombocytopenia.

Antigens, Surface↗
PubMed1998

Initiation of the autologous mixed lymphocyte reaction requires the expression of costimulatory molecules B7-1 and B7-2 on human peripheral blood dendritic cells.

The human autologous mixed lymphocyte reaction (AMLR) consists of a proliferative response of primarily CD4+ T lymphocytes stimulated by autologous non-T cells expressing class II MHC-encoded gene products and is thought to represent a self-recognitive mechanism that might be important in regulating the cellular interactions involved in the generation of normal immune responses. To further define appropriate stimulator cell populations, as well as the molecular mechanism responsible for the initiation of AMLR, we compared the T cell-stimulatory capacity of highly purified populations of peripheral blood dendritic cells (DCs) and monocytes (Mos) under serum-free conditions, thus carefully avoiding the presence of xenogeneic Ags. Whereas both freshly isolated Mos and DCs were found to be poor stimulators of autologous T cell proliferation, preactivation of DCs, but not of Mos, for 48 h with granulocyte-macrophage CSF led to a 113-fold increase in DC stimulatory capacity. AMLR was inhibited by mAbs against HLA-DR and CD4 molecules, and, in addition, showed a higher dependence on the granulocyte-macrophage CSF-induced up-regulation and/or de novo expression of the costimulatory molecules B7-2 and, in particular, B7-1 as compared with an Ag-specific or allogeneic MLR. Thus, our data suggest that the high density of costimulatory molecules together with MHC class II molecules on competent APCs appear to be the major triggers for the initiation of AMLR.

Antigen Presentation↗