PubMed Health⌕ Search

Biomedical subjects

L M Knudsen

Publications and source records attributed to L M Knudsen.

At least 19 recordsLinked to original sources
PubMed2006

Quality assessment of autografting by probability evaluation: model estimation by clinical end-points in newly diagnosed multiple myeloma patients.

BACKGROUND: Pre-transplant clinical evaluation of autografting is an important step in predicting post-transplant support, complications and safety. Today, unfavorable outcomes such as early death or graft failure are rare, making them unsuitable for quality assessment of supportive autografting. However, end-points constructed from frequently occurring clinical events may estimate clinically relevant prognostic models. METHODS: The present retrospective analysis was based on two consecutive clinical trials in the Nordic area including up to 640 newly diagnosed multiple myeloma patients. RESULTS: In the model, the efficacy (time on antibiotics and use of transfusions) was influenced by pre-transplant variables, including sex, nationality, serum creatinine, hemoglobin, disease stage at diagnosis, response following induction therapy, length of priming and average graft CD34+ cell number per day of harvest. The toxicity end-point (time to blood cell recovery) was influenced by nationality, marrow plasma cell percentage, serum creatinine, M-component isotype, response to induction therapy, length of priming and graft CD34+ cell number. The safety (early disease recurrence or death) was influenced by serum creatinine, hemoglobin, treatment response and CD34+ cell number. DISCUSSION: In conclusion, the model illustrates that intervention strategies in quality assessment of autografting may benefit from probability estimates of graded clinical end-points.

Clinical Trials as Topic↗
PubMed2001

[Posttraumatic hyphema induced by tossed frozen caramel candy].

The tossing of caramels is a traditional part of the celebrations on the last day of school. A case in which a 14-year-old boy suffered a secondary posttraumatic hyphaemia induced by a caramel tossed at the patient's left eye is described. The condition remitted spontaneously without loss of eyesight.

Adolescent↗
PubMed2001

Kinetic studies during peripheral blood stem cell collection show CD34+ cell recruitment intra-apheresis.

A sufficient number of CD34+ cells in the peripheral blood stem cell product is important to achieve a rapid and sustained engraftment. The purpose of the present work was to study CD34+ cell kinetics during leukapheresis. Blood samples before and after leukapheresis were analysed for CD34+ cells in 205 procedures. The number of CD34+ cells after plus the number of CD34+ cells harvested was 1.5-fold greater than the number available at the beginning of the procedure, indicating recruitment of CD34+ cells during leukapheresis. In a subgroup of 66 procedures, granulocytes and platelets were measured. In contrast to CD34+ cells, these cell fractions were not recruited to the blood stream during leukapheresis. An additional nine patients were studied with serial blood measurements during leukapheresis, showing an initial decline that was followed by an increase in CD34+ cells during leukapheresis. In conclusion, CD34+ cells are recruited to the blood during the leukapheresis procedure in contrast to granulocytes and platelets.

Adolescent↗
PubMed2001

Health-related quality of life in multiple myeloma patients receiving high-dose chemotherapy with autologous blood stem-cell support.

In a population-based study, the Nordic Myeloma Study Group found a survival advantage for high-dose melphalan with autologous blood stem-cell support compared to conventional chemotherapy in myeloma patients under 60 yr of age (risk ratio: 1.62; confidence interval [CI] 1.22-2.15; p = 0.001). A study of health-related quality of life (HRQoL) was integrated in the trial, using the EORTC QLQ-C30 questionnaire. Of the 274 patients receiving intensive therapy 221 (81%) were compared to 113 (94%) of 120 patients receiving conventional melphalan-prednisone treatment. Prior to treatment, there were no statistically significant differences in any HRQoL score between the two groups. One month after the start of induction chemotherapy, the patients on intensive treatment had more sleep disturbance than the control patients. At 6 mo, corresponding to a mean of 52 d after high-dose melphalan, the patients on intensive treatment had moderately lower scores for global QoL and role and social functioning and there was also a significantly higher score for appetite loss. At 12 and 24 mo, the HRQoL was similar to that of the control patients. At 36 mo, there was a trend toward less fatigue, pain, nausea, and appetite loss in the intensive-treatment group. Thus, the 18 mo of prolonged survival seem to be associated with a good health-related quality of life. Despite the moderate HRQoL reduction associated with the early intensive chemotherapy phase, this treatment modality must be regarded as an important step forward in the care of multiple myeloma.

Adult↗
PubMed2000

Renal failure in multiple myeloma: reversibility and impact on the prognosis. Nordic Myeloma Study Group.

The purpose of the present study was to analyse the importance and prognostic value of renal failure in multiple myeloma patients. The frequency and reversibility of renal failure in 775 multiple myeloma patients diagnosed between 1984-86 and 1990-92 in the Nordic countries were studied. Renal failure, defined as plasma creatinine > 130 micromol/l, was observed in 29% of the cases at the time of diagnosis. During the first year after diagnosis 58% achieved normalisation of p-creatinine, and this was achieved mainly during the first 3 months. Reversibility of renal failure was more frequently observed in patients with moderate renal failure, hypercalcaemia and low Bence-Jones protein excretion. In a multivariate analysis renal failure, high age, stage III disease and hypercalcaemia were independent prognostic factors for survival. Patients who needed dialysis had a poor prognosis, with a median survival of 3.5 months. A 12-months landmark analysis showed that reversibility of renal failure was a more important prognostic factor than response to chemotherapy. It is concluded that renal failure in multiple myeloma is reversible in about half the cases, and reversibility of renal failure improves long-term survival.

Adult↗
PubMed1999

Reduced bone marrow stem cell pool and progenitor mobilisation in multiple myeloma after melphalan treatment.

The content of stem cells was analysed in bone marrow samples from 75 multiple myeloma patients. In unstimulated bone marrow the percentage of CD34+ cells was significantly reduced in 11 patients previously treated with melphalan-prednisolone (MP)(median= 0.15%) compared to median 0.87% in 31 untreated patients (P=0.0001). The bone marrow cellularity in the two groups did not differ. There was no correlation between the number of courses or total dose of melphalan and content of CD34+ cells in the bone marrow. The clonogenicity as well as the ability to expand the marrow stem cell pool during growth factor treatment were also reduced in MP treated patients compared to untreated patients. Analysis of different subsets of CD34+ cells revealed no influence on the pre B cell compartment in the bone marrow by MP treatment, but the committed stem cells (CD34+CD38+) were reduced more than the uncommitted stem cells (CD34+CD38-) in the MP treated group compared to the untreated patients. Mobilisation to and harvest of total number of CD34+ cells from peripheral blood was also reduced in the MP treated group. There was, however, no difference in the distribution between CD34+CD38+ and CD34+CD38- populations in the leukapheresis products in the untreated and the melphalan-treated group, suggesting selective mobilisation of CD34+CD38+ cells and/or differentiation of CD34+CD38-cells during growth factor stimulation. We conclude that melphalan decreased the number of stem cells in the bone marrow, the ability to expand the stem cell pool and mobilise stem cells to the pheripheral blood.

Adult↗
PubMed1999

Selective loss of progenitor subsets following clinical CD34+ cell enrichment by magnetic field, magnetic beads or chromatography separation.

In this preclinical evaluation we have compared the efficacy of three clinical CD34+enrichment procedures with respect to purity, yield and recovery, as well as risk of selective loss of CD34+ lineage-specific subsets. The three devices work by different principles and have several different manipulation steps: The magnetic field separator uses paramagnetic iron-dextran particles; the magnetic microbead selection is based on the advantage of a large surface area for immobilisation of the monoclonal antibody within a very small volume; the original immunoabsorption technique is based on the use of biotinylated antibody applied to a column of avidin-coated sephadex beads. The results of this evaluation gave a median purity 96% (88-98%), 86% (62-97%), and 49% (18-85%), and median yield of 65% (54-100%), 40% (21-74%), and 30% (8-55%), respectively. Subset analysis recognised a selective loss of CD34+/61+ after enrichment, most likely due to class I-II antibodies used for the enrichment step or, alternatively, nonspecific binding of megakaryocytic progenitors. Tumour cell spiking experiments on a clinical scale documented an expected 2-4 log reduction resulting in a number of potentially malignant cells in the CD34 enriched product. Our data support four major conclusions: First, that magnetic field separation is superior to magnetic beads and chromatography selection, mainly due to the risk of cell loss and insufficient recovery with the two latter methods. Second, that late differentiated progenitors with CD34 class III epitopes present are lost during the enrichment procedures. The third major conclusion is that chromatography selection results in a selective loss of CD34bright cells, which are most likely uncommitted early progenitors. This was an unexpected finding which may be a consequence of an imbalance between the strong forces between biotin-avidin and insufficient physical manipulation for CD34+ cell release. Finally, the data document that CD34 selection alone is an inappropriate way to eliminate tumour cells due to the uncontrolled variables and the inconsistent outcome. The only products which can be expected to be purged free of tumour cells are the ones with very minimal (<10-5) contamination in the starting products, ie products documented tumour free with the most sensitive techniques for quantitation. If this is not the case, the optimal purging strategy may be a two-step procedure including CD34 selection and subsequent depletion of the tumour cells in question.

Antigens, CD34↗
PubMed1999

High numbers of clonal CD19+ cells in the peripheral blood of a patient with multiple myeloma.

Recent studies concerning the numbers of circulating clonal B cells in patients with multiple myeloma (MM) have reported conflicting data regarding the exact levels of clonal B cells and the existence of clonal cells in the CD34 compartment. In this report we show that high numbers of clonal cells with a phenotype of late-stage B cells or pre-plasma cells were present in the peripheral blood (PB) of a patient with MM. During treatment the initial high level of PB clonal cells was markedly reduced and remained low (<1%) post transplant, even after disease progression. In addition, we found that the MM clone did not include a B-progenitor population defined by CD34.

Antigens, CD19↗
PubMed1998

["Moon-cars" are dangerous].

We investigated the number and seriousness of moon-car accidents in our region (a moon-car is a toy-vehicle, see Fig. 1). The study was retrospective combined with a telephone-interview. Forty-seven patients were seen in the emergency room after a moon-car accident in the period 1/1 1990-31/12 95. There were 12 fractures, including five fractures of the tibial shaft and one supracondylar humeral fracture which was operated. There were 17 wounds, 14 of which were sutured. Seventeen patients had distorsions/contusions, three cases of head contusions (observed for concussion) and two with teeth damages. We found that the number of moon-car accidents is increasing (13 patients the last year), and that the accidents are not only minor. New rules in day care centres should be able to especially limit the number of more serious accidents.

Accidents↗
PubMed1998

Evaluation of mobilized CD34+ cell counts to guide timing and yield of large-scale collection by leukapheresis.

We have previously reported a more than 50% risk of insufficient harvests (< 2 x 10(6) CD34+ cells/kg) following a fixed timing of leukapheresis in an unselected patient population collected for autologous stem cell transplantation. The failures were easily identified as patients who had < 20,000/ml CD34+ blood cells at the time of harvest. Consequently, in an attempt to optimize the timing strategy, we decided to perform daily analysis of the blood levels and perform leukapheresis within 24 h after the blood cell count exceeded 20,000 CD34+/ml. The results of this prospective study showed (a) that leukapheresis collections that were initiated based on the CD34+ blood level resulted in a success rate of 85% following 1-3 day harvests, (b) that high-level mobilizers with > 80,000 CD34+ cells/ml can be harvested successfully by only one procedure, and (c) that low-level mobilizers with < 40,000 CD34+ cells/ml still have a high risk of inadequate harvests. In summary, the optimized timing strategy is effective, but there is still room for improvement. First, new potent priming procedures for low-level and bad mobilizers are required, and second, algorithms to reduce the leukapheresis volume and time for high-level mobilizers should be established.

Adolescent↗
PubMed1998

CD34+ subset and tumor cell quantitation by flow cytometry--step toward quality assessment of autografts in B cell malignancies.

To day it is possible to predict the probability of fast engraftment based on a very simple flow cytometry standard analysis of CD34+ cells as documented by the 28 laboratories within the NSCL-G. However, the risk for delayed platelet engraftment still needs to be predicted in clinical practice for patients receiving less than 10 x 10(6) CD34+ cells/kg. Here we present data from our center supporting that identification by double staining of uncommitted (CD34+/CD38-) and lineage specific (CD34+/CD61+) progenitors may allow us to predict patients at high risk for prolonged platelet recovery. Following high dose therapy more than 30% of patients with haematological malignancies do suffer from disease recurrence within the first 3-6 months following high dose therapy. Today there are strong indications that such patients may have been transplanted with an autograft contaminated with a high number of potentially malignant B cells. Here we present a novel methodology for quantitation of blood circulating tumor cells by combining flow cytometry, cell sorting, limiting dilution and single cell RT-PCR. Such methodology has documented mobilization of clonal B cells following priming of the peripheral blood stem cell harvest and it can be used to identify minor populations and predict the efficacy of patient specific purging strategy. Consequently, quality assessment of autografts may include techniques which can predict fast three lineage engraftment as well as the risk for prolonged platelet recovery and can identify the group of patients/autografts with a strong contamination of potential tumor cells with a risk of early relapse. The future supportive cell therapy may depend upon improvements of such technologies and strategies including the selective administration of lineage specific growth factors e.g., trombopoietin as well as patient specific controlled purging strategies.

Antigens, CD19↗
PubMed1998

Comparison of rhG--CSF primed bone marrow and blood stem cell autografts: an analysis of engraftment in malignant lymphomas and solid tumours.

Many studies have documented faster engraftment after transplantation with peripheral blood stem cells (PBSC) compared to bone marrow (BM) stem cells. Most comparisons, however, have been between unprimed BM and primed PBSC. We have collected engraftment data on 39 patients from 4 Danish centres and compared G-CSF primed BM with G-CSF primed PBSC in malignant lymphoma and solid tumours. In the lymphoma group 6 BM transplants were compared with 8 PBSC transplants, whereas in the testicular cancer group 16 BM transplants were compared with 9 PBSC transplants. In the lymphoma group, the time to platelet engraftment (platelets >20x10(9)/l unsupported) was median 15 d in PBSC transplants and median 34 d in BM transplants (p=0.003). In the solid tumour patients the difference in time to platelet engraftment was 11 and 18 d in PBSC and BM transplants, respectively (p<0.0001). In an attempt to explain this difference we performed CD34+ subset analysis of BM and PBSC. This analysis revealed a higher content of lineage restricted cells (CD34+CD61+ and CD34+GlyA+) in PBSC compared to BM. In conclusion, G-CSF mobilized PBSC seems to result in faster engraftment than G-CSF primed BM, which could be explained by an increased number of lineage specific progenitors in PBSC compared to BM.

Adolescent↗
PubMed1996

In-vitro clonogenicity of mobilized peripheral blood CD34-expressing cells: inverse correlation to both relative and absolute numbers of CD34-expressing cells.

The determination of CD34-expressing cells by multiparameter flow cytometry is now widely used to estimate the reconstitution potential of cells harvested by cytapheresis for peripheral blood stem cell and progenitor cell transplantation. There is a correlation between the number of CD34-expressing cells collected and committed progenitor cells (CFU-GM and BFU-E) capable of forming colonies in vitro, but there is considerable variation in the proportion of CD34-expressing cells capable of clonogenic growth. The data in this study of 782 cytapheresis samples indicates that there is a negative correlation between the clonogenicity of the CD34-expressing cells and the absolute number or the proportion of CD34-expressing cells within the harvest. In 116 samples the proportion of CD34-expressing cells co-expressing the CD45-RA-antigen (a subset of CD34-expressing cells which includes virtually all clonogenic cells in terms of CFU-GM) was determined, but this did not help to identify the clonogenicity of a given sample. These findings may have clinical relevance, particularly when mobilization is judged to be relatively poor or when a good harvest is to be divided for multiple high-dose procedures.

Antigens, CD34↗
PubMed1996

Nordic flow cytometry standards for CD34+ cell enumeration in blood and leukapheresis products: report from the second Nordic Workshop. Nordic Stem Cell Laboratory Group (NSCL-G).

Recently, Nordic protocols have been activated for the use of high-dose chemotherapy and radiotherapy to treat newly diagnosed young patients with multiple myeloma, breast cancer, and malignant lymphomas. The protocols include transplantation of autologous stem cells or progenitors as supportive therapy. This requires a safe number and optimal quality of the harvested cells. Consequently, the Nordic stem cell laboratories established a collaboration to optimize enumeration of CD34+ cells by flow cytometry. In the first workshop (WS-I) report, we addressed the issue of standardization of technical variables. Taking into consideration the variations in estimation of progenitors, a safe graft should contain > 2.0 x 10(6) CD34+ cells per kilogram patient weight, harvested by two or three leukaphereses. This report presents the results from the second workshop (WS-II). Twelve blood or leukapheresis products were shipped and analyzed in 24 stem cell laboratories, and all results were returned to a central database at Herlev Hospital, Copenhagen. The data documented a significant correlation between CD34+ cell enumerations of the 12 samples analyzed in each of the 24 different stem cell laboratories within the Nordic stem cell laboratory group (NSCL-G). At a practical workshop, the NSCL-G developed a standard for the performance of CD34 enumeration. This is based on the simple Milan Protocol, which uses the anti-HPCA-2PE marking of CD34+ (FL-2) nongranulated (lowSSC) cells. The NSCL-G has decided to hold a third workshop (WS-III) to establish working recommendations for double marking of CD34+ lineage-specific subsets and for handling cellular material for storage of RNA and DNA from blood and leukapheresis products.

Antigens, CD34↗
PubMed1996

Improved priming for mobilization of and optimal timing for harvest of peripheral blood stem cells.

The time of stem cell harvest and the mobilization regimen may play important roles in terms of achieving adequate numbers of stem cells by leukapheresis. To optimize the timing of leukapheresis, we have determined simultaneously the number of CD34+ cells in the peripheral blood as well as in the leukapheresis product of 214 apheresis procedures performed in 66 unselected patients with malignant hematologic diseases and solid tumors. A significant correlation between the number of CD34+ cells in peripheral blood and the leukapheresis product (R = 0.8) was found. The presence of more than 20 x 10(3)/ml blood CD34+ cells gave a sufficient yield (> or = 1.0 x 10(6) CD34+ cells/kg) in 81% of the cases. In an attempt to compare two priming regimens, we performed leukapheresis twice in 12 patients with stable disease. In the first sequence, stem cells were mobilized with rhG-CSF (10 micrograms/kg/day) alone and, in the second sequence, with cyclophosphamide (4 g/m2) plus rhG-CSF. A significantly higher yield of CD34+ cells and a better correlation between CD34+ cells in the peripheral blood and the leukapheresis product were found after priming with high-dose cyclophosphamide plus rhG-CSF, compared with priming with rhG-CSF alone. In a multivariate analysis, three factors were found to correlate with the yield of CD34+ cells, namely prior chemotherapy, bone marrow function, and the mobilization regimen. The use of cyclophosphamide priming improves CD34+ mobilization, and the introduction of blood CD34+ level optimizes the timing for harvest of stem cells, which should be performed early during treatment of malignancies.

Adolescent↗
PubMed1995

[Hematologic regeneration after high dose chemotherapy. Use of peripheral blood stem cells].

High dose chemotherapy supported by haematopoietic stem cells is increasingly used for a variety of malignancies. Peripheral blood stem cells (PBSC) are replacing bone marrow stem cells in autologous transplantations. In this paper we report our experiences with transplantations using PBSC with respect to haematopoietic recovery. Forty-nine patients with breast cancer and different malignant haematological diseases receiving autologous transplantations with three different sources of haematopoietic stem cells were compared for engraftment parameters. Between 1989 and 1992, 27 patients were transplanted with autologous bone marrow stem cells alone (group 1) followed by 11 patients transplanted with bone marrow stem cells and PBSC (group 2) and subsequently 11 patients transplanted with PBSC alone (group 3). The median times to achieve granulocyte level > 0.5 x 10(9)/l posttransplant were 22 days for group 1, 10 days for group 2 and 13 days for group 3. The median times to achieve platelet level > 20 x 10(9)/l unsupported posttransplant were 30 days for group 1, 16 days for group 2 and 15 days for group 3. In conclusion, haematopoietic recovery was faster in patients receiving PBSC than in a control group of 27 patients receiving bone marrow stem cells alone.

Adult↗