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N Jacobsen

Publications and source records attributed to N Jacobsen.

At least 55 records · Page 3Linked to original sources
PubMed1997

Long-term results after allogeneic bone marrow transplantation for chronic myelogenous leukemia in chronic phase: a report from the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation.

The purpose of this study was to determine the long-term results of allogeneic bone marrow transplantation for chronic myeloid leukemia. A retrospective analysis was carried out of the outcome of 373 consecutive transplants performed at 38 European institutions between 1980 and 1988 and reported to the registry of the European Group for Blood and Marrow Transplantation. All transplants were carried out for first chronic phase of chronic myelogenous leukemia using unmanipulated marow cells from HLA-identical sibling donors. The probability of survival and leukemia-free survival at 8 years were 54% (95% CI: 49-59) and 47% (95% CI: 41-52) respectively. The probabilities of developing acute GVHD (II-IV) at 100 days and chronic GVHD at 4 years after transplant were 47% (95% CI: 41-53) and 52% (95% CI: 46-58) respectively. The probabilities of transplant-related mortality and leukemic relapse 8 years after BMT were 41% (95% CI: 36-48) and 19% (95% CI: 14-25), respectively. Transplant within 12 months of diagnosis was associated with reduced transplant-related mortality (34 vs 45%, P = 0.013) and resulted in improved leukemia-free survival (52 vs 44%, P = 0.03). The probability of relapse was significantly reduced in patients who developed chronic GVHD (RR = 0.33, P = 0.004). The probability of relapse occurring more than 2 years after transplant was increased more than five-fold in patients transplanted from a male donor (RR = 5.5, P = 0.006). Sixty-seven patients in hematologic remission were studied for residual disease by two-step RT/PCR for BCR-ABL mRNA and 61 (91%) tested negative. We conclude that bone marrow transplantation can induce long-term survival in approximately one-half of CML patients; the majority of survivors have no evidence of residual leukemia cells when studied by molecular techniques. The probability of late relapse is increased with use of a male donor.

Adolescent↗
PubMed1997

Allogeneic bone marrow transplantation for chronic myelomonocytic leukemia in childhood: a report from the European Working Group on Myelodysplastic Syndrome in Childhood.

PURPOSE: To evaluate the role of allogeneic bone marrow transplantation (BMT) in children with chronic myelomonocytic leukemia (CMML). PATIENTS AND METHODS: Forty-three children with CMML given BMT and reported to the European Working Group on Myelodysplastic Syndrome in Childhood (EWOG-MDS) data base were evaluated. In 25 cases, the donor was a human leukocyte antigen (HLA)-identical or a one-antigen-disparate relative, in four cases a mismatched family donor, and in 14 a matched unrelated donor (MUD). Conditioning regimens consisted of total-body irradiation (TBI) and chemotherapy in 22 patients, whereas busulfan (Bu) with other cytotoxic drugs was used in the remaining patients. RESULTS: Six of 43 patients (14%), five of whom received transplants from alternative donors, failed to engraft. There was a significant difference in the incidences of chronic graft-versus-host disease (GVHD) between children transplanted from compatible/one-antigen-mismatched relatives and from alternative donors (23% and 87%, respectively; P < .005). Probabilities of transplant-related mortality for children given BMT from HLA-identical/one-antigen-disparate relatives or from MUD/ mismatched relatives were 9% and 46%, respectively. The probability of relapse for the entire group was 58%, whereas the 5-year event-free survival (EFS) rate was 31%. The EFS rate for children given BMT from an HLA-identical sibling or one-antigen-disparate relative was 38%. In this latter group, patients who received Bu had a better EFS compared with those given TBI (62% v 11%, P < .01). CONCLUSION: Children with CMML and an HLA-compatible relative should be transplanted as early as possible. Improvement of donor selection, GVHD prophylaxis, and supportive care are needed to ameliorate results of BMT from alternative donors.

Bone Marrow Transplantation↗
PubMed1997

Results of allogeneic bone marrow transplants for leukemia using donors other than HLA-identical siblings.

PURPOSE: To compare outcomes of bone marrow transplants for leukemia from HLA-identical siblings, haploidentical HLA-mismatched relatives, and HLA-matched and mismatched unrelated donors. PATIENTS: A total of 2,055 recipients of allogeneic bone marrow transplants for chronic myelogenous leukemia (CML), acute myelogenous leukemia (AML), and acute lymphoblastic leukemia (ALL) were entered onto the study. Transplants were performed between 1985 and 1991 and reported to the International Bone Marrow Transplant Registry (IBMTR). Donors were HLA-identical siblings (n = 1,224); haploidentical relatives mismatched for one (n = 238) or two (n = 102) HLA-A, -B, or -DR antigens; or unrelated persons who were HLA-matched (n = 383) or mismatched for one HLA-A, -B, or -DR antigen (n = 108). HLA typing was performed using serologic techniques. RESULTS: Transplant-related mortality was significantly higher after alternative donor transplants than after HLA-identical sibling transplants. Among patients with early leukemia (CML in chronic phase or acute leukemia in first remission), 3-year transplant-related mortality (+/-SE) was 21% +/- 2% after HLA-identical sibling transplants and greater than 50% after all types of alternative donor transplants studied. Among patients with early leukemia, relative risks of treatment failure (inverse of leukemia-free survival), using HLA-identical sibling transplants as the reference group, were 2.43 (P < .0001) with 1-HLA-antigen-mismatched related donors, 3.79 (P < .0001) with 2-HLA-antigen-mismatched related donors, 2.11 (P < .0001) with HLA-matched unrelated donors, and 3.33 (P < .0001) with 1-HLA-antigen-mismatched unrelated donors. For patients with more advanced leukemia, differences in treatment failure were less striking: 1-HLA-antigen-mismatched relatives, 1.22 (P = not significant [NS]); 2-HLA-antigen-mismatched relatives, 1.81 (P < .0001); HLA-matched unrelated donors, 1.39 (P = .002); and 1-HLA-antigen-mismatched unrelated donors, 1.63 (P = .002). CONCLUSION: Although transplants from alternative donors are effective in some patients with leukemia, treatment failure is higher than after HLA-identical sibling transplants. Outcome depends on leukemia state, donor-recipient relationship, and degree of HLA matching. In early leukemia, alternative donor transplants have a more than twofold increased risk of treatment failure compared with HLA-identical sibling transplants. This difference is less in advanced leukemia.

Age Factors↗
PubMed1997

The immunodeficiency after allogeneic bone marrow transplantation in man: role of cytokines.

The effect of various cytokines including rIL-1, rIL-2, rIL-3, rIL-4, rIL-6, and growth factors including rNGF, rILGF and rEPGF on the post transplant immunodeficiency after allogeneic bone marrow transplantation was explored in 8 patients. The results show that neither cytokine alone was able to increase the proliferative capability in post transplant lymphocytes, however, when added in conjunction a significant increase in PHA driven proliferation was noted. Any significant lack of growth factors is probably not the only cause of immunodeficiency post transplant, since addition of any of these compounds did not have any influence on the lymphocyte proliferation, and so the data presented here suggest that therapeutic application of any of the investigated cytokines or growth factors to such patients is unlikely to be successful in overcoming the defects of T cell function post grafting.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Glycerophosphorylethanolamine (GPEA) identified as an hepatocyte growth stimulator in liver extracts.

Extracts from weanling pig liver were found to act synergistically with growth factors such as hepatocyte growth factor and transforming growth factor-alpha to stimulate hepatocyte growth in serum-free cultures. In the absence of added growth factors, the extracts had no activity. The compound responsible for this activity was isolated by passing heat-treated liver extract through anion-exchange and heparin columns followed by gel filtration at neutral and low pH, reversed-phase HPLC, and a final gel filtration column at low pH. The activity was followed throughout the purification by its ability to increase substantially the incorporation of [3H]thymidine into primary rat hepatocytes cultured serum-free in the presence of hepatocyte growth factor. The active compound was identified by NMR and mass spectrometry as glycerophosphorylethanolamine (GPEA), a breakdown product of the phospholipid phosphatidylethanolamine. The ethanolamine portion of the molecule was critical for the observed activity, whereas the glycerol phosphate portion was not necessary. In the absence of added growth factors, neither GPEA nor ethanolamine had any stimulatory effect on the cells. These results demonstrate that hepatocytes grown in culture, and especially those grown in serum-free media, require a supplement of ethanolamine and/or GPEA. In the absence of these compounds, their response to growth stimuli is greatly reduced.

Animals↗
PubMed1996

Chronic neutrophil leukaemia in adolescence and young adulthood.

Chronic neutrophil leukaemia (CNL) is a rare myeloproliferative disorder predominantly reported in elderly patients. We present a 15-year-old girl and a 25-year-old male with CNL. Clonal cytogenetic abnormalities were detected in both patients. One showed trisomy 21 evolving into tetrasomy 21. The second patient showed a unique chromosome aberration during blast crisis: t(2;2)(q32;p24). Both patients were successfully treated with allogeneic bone marrow transplantation (BMT). CNL should also be considered as a differential diagnosis in adolescence and young adulthood. BMT represents a potentially curative treatment option in such patients.

Adolescent↗
PubMed1996

Association study of bipolar disorder at the phospholipase A2 gene (PLA2A) in the Darier's disease (DAR) region of chromosome 12q23-q24.1.

We have previously described a pedigree in which affective disorder and Darier's disease cosegregate and, in an independent sample of 45 bipolar pedigrees, reported evidence in support of linkage between a putative susceptibility locus for bipolar disorder and markers in the Darier's disease region of chromosome 12q23-q24.1. The maximum evidence for linkage was given by a polymorphism at the gene encoding secretory phospholipase A2 (PLA2A), a candidate gene for affective disorder. Dawson et al. (Psychiatric Genetics, 5, 177-180) recently reported allelic association with the same polymorphism at PLA2A in a sample of 54 bipolar probands and 56 controls. We have been unable to replicate the association in 127 Caucasian British DSMIII-R bipolar probands and 223 Caucasian British controls. However, on the basis of several lines of evidence discussed in the paper, we believe that this genomic region in general, and the PLA2A gene in particular, are worthy of further study as candidates in the search for susceptibility genes for the functional psychoses.

Alleles↗
PubMed1996

Profile of work-related health complaints among Swedish dental laboratory technicians.

The purpose of the present investigation was to assess the prevalence and nature of occupation-related health problems among Swedish dental laboratory technicians. A 4-page questionnaire listing seven groups of health complaints was completed by 489 male and 242 female technicians, representing 56% of the active members of their organization. Similar information from 163 males and 160 females with other occupations was used for comparison. The biannual prevalence of health problems among the technicians was 79%, comprising musculoskeletal (68%), dermal (34%), respiratory 31%, neurological (26%), systemic (19%) and eyesight/hearing problems (15%). Job-specific ergonomic and stress factors were responsible for musculoskeletal and neurological (finger) reactions whereas chemical insults, grinding dusts and indoor climate caused dermal, respiratory and systemic reactions. There was no age prevalence as regards health complaints, but female technicians consistently showed a large prevalence of musculoskeletal, dermal systemic and neurological complaints than their male counterparts (P < 0.05, chi2). A similar sex difference was also present in the control group. A considerable part of the reactions were perceived to be of minor importance, bringing the total biannual prevalence down to 57%. However, the prevalence of job-related health complaints was still higher among the technicians than in control groups for all indicators except systemic and eyesight/hearing problems. The profile of health complaints among dental laboratory technicians was characterized by musculoskeletal, neurological and dermal reaction, underlining the importance of job-specific ergonomic and chemical hazards. Only a few of the technicians had consulted medical personnel.

Adult↗
PubMed1996

Lung function after allogeneic bone marrow transplantation for leukaemia or lymphoma.

Longitudinal data were analysed on the lung function of 25 of 29 survivors of childhood leukaemia or lymphoma, who had been conditioned with cyclophosphamide and total body irradiation before allogeneic bone marrow transplantation, to test whether children are particularly vulnerable to pulmonary damage after transplantation. None developed chronic graft-versus-host disease. Transfer factor and lung volumes were reduced immediately after bone marrow transplantation, but increased during the following years. However, at the last follow up, 4-13 years (median 8) after transplantation, patients had significantly reduced transfer factor, total lung capacity, and forced vital capacity (-1.0, -1.2, and -0.8 SD score, respectively), and increased ratio of forced expiratory volume in one second to forced vital capacity (+0.9 SD score). None of the patients had pulmonary symptoms, and changes were unrelated to their age at bone marrow transplantation. In conclusion, patients had subclinical restrictive pulmonary disease at a median of eight years after total body irradiation and allogeneic bone marrow transplantation.

Adolescent↗
PubMed1996

Chemotherapy versus transplants for acute myelogenous leukemia in second remission.

The best therapy for persons with acute myelogenous leukemia (AML) in 2nd remission is unknown. Bone marrow transplants from an HLA-identical sibling are reported to be better than chemotherapy but this is controversial. The objective of the study was to compare 3-year leukemia-free survival (LFS) in comparable subjects receiving chemotherapy or a transplant. 485 persons with AML in 2nd remission were studied. The chemotherapy cohort included 244 persons treated on trials of the British Medical Research Council, Eastern Cooperative Oncology Group and MD Anderson Hospital. The transplant cohort included 257 persons transplanted worldwide and reported to the international Bone Marrow Transplant Registry (16 were also chemotherapy subjects.) Subjects were selected for comparable age and year of treatment. Preliminary analyses identified two factors correlated with LFS: age < or = or > 30 years and 1st remission duration < or = or > 1 year; subsequent analyses were partitioned accordingly. Three-year probabilities of treatment-related mortality with chemotherapy and transplants were 7% (95% confidence interval, 3-15%) vs 56% (49-63%). Three-year leukemia relapse probabilities were 81% (74-86%) vs 41% (33-49%). Three-year probabilities of LFS were 17% (12-23%) vs 26 (20-32%). Cohort analysis showed significantly higher LFS with transplants vs chemotherapy in persons < or = 30 years and 1st remissions > 1 year (41% (29-53%) vs 17% (7-32%); P = 0.017) and those in > 30 years with 1st remissions < or = 1 year (18% (9-29%) vs 7% (2-16%); P = 0.046). Others had comparable LFS with both treatments. These data indicate better LFS with HLA-identical sibling transplants than chemotherapy in some persons with AML in 2nd remission.

Adolescent↗
PubMed1996

Intensive chemotherapy in childhood myelodysplastic syndrome. A comparison with results in acute myeloid leukemia.

Myelodysplastic syndrome (MDS) in children is often considered as a variant of acute myeloid leukemia (AML) and frequently treated as such. However, there are very few reported data on the outcome following AML treatment. We analyzed 20 consecutive cases of de novo MDS treated in Denmark according to the NOPHO AML protocols. The results were compared with those obtained in 31 children with de novo AML treated with the same protocols, and with the outcome in 10 children with MDS who received allogeneic bone marrow transplantation (BMT) without prior AML therapy. Distinction between MDS and AML was made morphologically according to the FAB criteria. All children were followed for at least 37 months. The proportion of complete remission in MDS and AML was 35 percent vs 74 percent. (P = 0.005), resistant disease 25 percent vs 10 percent (P = 0.14), death in cytopenia 40 percent vs 16 percent (P= 0.06), and 3-year survival 15 percent vs 35 percent. (P = 0.11), respectively. Duration of treatment-related cytopenia was similar in MDS and AML, except for a longer period of leukopenia in MDS following the second course of induction. Seven of 10 MDS children receiving BMT without prior chemotherapy are long-term survivors. Our data suggest that conventional AML regimens are associated with a low rate of complete remission, a high risk of death in cytopenia, and a limited curative potential in childhood MDS. Allogeneic BMT was in contrast associated with a high survival rate. BMT may, at least in some patients, be performed successfully without prior induction chemotherapy. The different response to therapy in MDS and AML may reflect fundamental biological differences between the two conditions.

Acute Disease↗
PubMed1996

Growth, growth hormone and final height after BMT. Possible recovery of irradiation-induced growth hormone insufficiency.

The aim of the present study was to assess growth, final height, growth hormone (GH) secretion and growth factors after BMT including TBI in childhood. The median age of the 25 participants was 11.3 years at BMT, and a median of 7.5 years had elapsed since BMT. The median height standard deviation score (SDS) declined significantly from diagnosis until 4 years after BMT (n = 25, P = 0.015), and decreased 1.08 SDS from diagnosis until final height (n = 14, P = 0.030). Sitting height to standing height ratio was impaired, -0.64 SDS, P < 0.05. GH insufficiency was found in 32% at follow-up. Repeated assessments of GH production over the years indicated improvement in GH secretion in nine individuals. Evaluation of spontaneous 24-h GH secretion indicated a secretory pattern similar to controls, although the total amount of GH secreted was lower. Neither insulin-like growth factor-1 (IGF-1) nor IGF binding protein-3 (IGFBP-3) alone could be used as a marker of GH insufficiency. IGF-1 was low: -1.18 SDS; (P < 0.001). In conclusion, our study demonstrated the impact on growth, final height, body proportions, GH secretion and growth factors after BMT including TBI. We hypothesize that children who receive BMT at a younger age are more at risk of loss of final height and abnormal body proportions. Our data indicate that some improvement in GH production may occur over the years.

Adolescent↗
PubMed1996

Treatment of relapse after allogeneic BMT with donor leukocyte infusions in 16 patients.

Sixteen patients with relapse after allogeneic BMT were treated with donor leukocyte infusions (DLI) from the original donor. The diagnoses at relapse were: CML in chronic phase (CP) (two patients), CML in accelerated phase (AP) (four patients), AML (four patients), MDS (one patient), ALL (four patients) and relapse of Hodgkin's disease (one patient). The patients received a mean of 5.2 x 10(8) leukocytes/kg with a range of 1.4-12.3 x 10(8) leukocytes/kg. Six patients obtained complete remission (CR), one with CML in CP, three with CML in AP, one MDS and one ALL. Partial remission (PR) was seen in three patients, one patient with CML in AP, one with AML and one with Hodgkin's disease. Seven patients had no response (NR) to the infusions, including one patient with CML in CP transplanted with a syngeneic donor. Four patients developed marrow hypoplasia after DLI (three CR and one PR) and two patients (ALL with CR and MDS with CR) were hypoplastic at relapse and marrow hypoplasia continued after DLI. GVHD occurred without GVL, but GVL only occurred in one patient with absence of GVHD. Eleven patients died of leukemia, six patients are alive. Three patients with CML are in CR 12, 12 and 32 months after DLI and one patient with ALL is in CR 15 months after DLI.

Adolescent↗
PubMed1996

Unifying plant molecular data and plants.

Located at a botanical department at an Agricultural University, our taxonomical and genetic research is mainly directed towards cultivated plants and their wild relatives. The investigations are usually under a common heading 'experimental taxonomy', and include basic systematics, cytogenetics, biodiversity, population dynamics, conservation and evolutionary questions correlating the wild species and the cultivated forms. Our point of initiation is the plants and questions/problems raised regarding these plants. Our way of approaching the problems is usually by applying different sets of data and testing them. Experimental taxonomy covers classical cytogenetics (chromosome counting and karyotyping) as well as molecular cytogenetic methods (RAPD, RFLP, in situ hybridization), and includes also chemical data on isoenzymes and anthocyanins. We have had good collaborations with other laboratories and found their expertise on the plants in question very helpful. The aim is always to unify various data on the same set of problems, in order to get a more complete understanding of the plants. At present the department is working on several, quite different plant genera, comprising herbs, aquatic plants, and trees. The methods vary, depending on the plants and the problems in question. Some of the current investigations concern the horticultural genera Lilium and Crocus, in which the main point of interest is the study of chromosome evolution using fluorescence in situ hybridization; preliminary investigations into the composition of anthocyanins in Crocus look very promising. In the tropical starch tuber crop Pachyrhizus (Fabaceae), molecular analyses of relationships between existing cultivars, landraces and wild material have been carried out. A genus which we, in cooperation with a number of other laboratories, have been working with for many years is Hordeum (Poaceae) with one cultivated species (barley) and 31 wild species. Here the main areas of investigation have been field studies and collecting, followed by a taxonomical treatment, hybridization experiments, cytogenetic analysis and isoenzyme studies. Within the field of forestry, we have used population genetics as a tool in the management of natural and domesticated populations and for conservation of genetic diversity. We have also ventured into the identification and use of DNA markers that are suited for genome mapping in Picea abies (Norway Spruce).

Cytogenetics↗
PubMed1996

Immunodeficiency after allogeneic bone marrow transplantation in man: the role of antigen presenting cells.

We investigated the proliferative response of donor T cells to phytohemagglutinin (PHA) presented by donor non-T cells in 7 patients after allogeneic bone marrow transplantation. Compared with the cellular response in the healthy marrow donors, T cell proliferation was found to be deficient in every recipient, from 130 to 739 days after grafting. Results of cell mixing experiments showed that the non-T cells of the patients were as capable as healthy donor non-T cells in presenting PHA to normal donor T cells. However, T cells from patients did not proliferate after substituting donor non-T cells for non-T cells from patients. This inability of T cells to proliferate was most likely the result of ineffective interactions among T cell subsets in patients after allogeneic bone marrow transplantation.

Adolescent↗
PubMed1996

Cytotoxic T cell activity after HLA-mismatch bone marrow transplantation.

Six patients with various hematologic diseases were treated with HLA-haploidentical bone marrow mismatched for 1-2 loci at the disparate chromosome with a relative response in the mixed lymphocyte reaction (MLR) ranging between 0.04 and 0.96 (median 0.27). Thirty to 371 days after bone marrow grafting, patient lymphocytes (of donor origin) were tested for reactivity in mixed lymphocyte culture (MLC) and cell mediated lympholysis (CMLy) to lymphocytes from the host (cryopreserved before grafting), the marrow donor, and unrelated individuals. After grafting, Lymphocytes from the patients showed a host-specific decrease in proliferation and in cytotoxic response (%51Cr release in a standard chromium release assay), when compared to the pretransplant host-specific donor response, whereas the responses towards third party cells were unaffected. This host-specific unresponsiveness after HLA-mismatch bone marrow transplantation is compatible with a clonal deletion theory and might be the reason that this procedure is at all possible.

Adolescent↗