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C Sundström

Publications and source records attributed to C Sundström.

At least 19 recordsLinked to original sources
PubMed2006

The G(-248)A polymorphism in the promoter region of the Bax gene does not correlate with prognostic markers or overall survival in chronic lymphocytic leukemia.

The G(-248)A polymorphism in the promoter region of the Bax gene was recently associated with low Bax expression, more advanced stage, treatment resistance and short overall survival in B-cell chronic lymphocytic leukemia (CLL), the latter particularly in treated patients. To investigate this further, we analyzed 463 CLL patients regarding the presence or absence of the G(-248)A polymorphism and correlated with overall survival, treatment status and known prognostic factors, for example, Binet stage, VH mutation status and genomic aberrations. In this material, similar allele and genotype frequencies of the Bax polymorphism were demonstrated in CLL patients and controls (n=207), where 19 and 21% carried this polymorphism, respectively, and no skewed distribution of the polymorphism was evident between different Binet stages and VH mutated and unmutated CLLs. Furthermore, no difference in overall survival was shown between patients displaying the G(-248)A polymorphism or not (median survival 85 and 102 months, respectively, P=0.21), and the polymorphism did not influence outcome specifically in treated CLL. Neither did the polymorphism affect outcome in prognostic subsets defined by VH mutation status or genomic aberrations. In conclusion, the pathogenic role and clinical impact of the Bax polymorphism is limited in CLL.

Adult↗
PubMed2005

Haematopoietic malignancies in rheumatoid arthritis: lymphoma risk and characteristics after exposure to tumour necrosis factor antagonists.

BACKGROUND: Patients with rheumatoid arthritis (RA) are at increased risk of malignant lymphomas, and maybe also of leukaemia and multiple myeloma. The effect of tumour necrosis factor (TNF) antagonists on lymphoma risk and characteristics is unclear. OBJECTIVE: To assess expected rates and relative risks of haematopoietic malignancies, especially those associated with TNF antagonists, in large population based cohorts of patients with RA. METHODS: A population based cohort study was performed of patients with RA (one prevalent cohort (n = 53,067), one incident cohort (n = 3703), and one TNF antagonist treated cohort 1999 through 2003 (n = 4160)), who were linked with the Swedish Cancer Register. Additionally, the lymphoma specimens for the 12 lymphomas occurring in patients with RA exposed to TNF antagonists in Sweden 1999 through 2004 were reviewed. RESULTS: Study of almost 500 observed haematopoietic malignancies showed that prevalent and incident patients with RA were at increased risk of lymphoma (SIR = 1.9 and 2.0, respectively) and leukaemia (SIR = 2.1 and 2.2, respectively) but not of myeloma. Patients with RA treated with TNF antagonists had a tripled lymphoma risk (SIR = 2.9) compared with the general population. After adjustment for sex, age, and disease duration, the lymphoma risk after exposure to TNF antagonists was no higher than in the other RA cohorts. Lymphomas associated with TNF antagonists had characteristics similar to those of other RA lymphomas. CONCLUSION: Overall, patients with RA are at equally increased risks for lymphomas and leukaemias. Patients with RA treated with TNF antagonists did not have higher lymphoma risks than other patients with RA. Prolonged observation is needed to determine the long term effects of TNF antagonists on lymphoma risk.

Adolescent↗
PubMed2003

Association between telomere length and V(H) gene mutation status in chronic lymphocytic leukaemia: clinical and biological implications.

The immunoglobulin V(H) gene mutation status can divide B-cell chronic lymphocytic leukaemia (CLL) into two entities with a different clinical course. Cases with unmutated V(H) genes, considered to evolve from pregerminal centre (GC) cells, have a worse outcome compared to cases showing mutated V(H) genes, that is, post-GC derived. Also, telomere length has been reported to be of prognostic significance in CLL. Interestingly, telomerase becomes activated during the GC reaction and an elongation of the telomeres occurs in GC B cells. We performed telomere length and V(H) gene analysis in a series of 61 CLL cases, in order to investigate if the unique telomere lengthening shown in GC B cells could reflect the telomere status in the two subsets of mutated and unmutated CLL. A novel association was found between V(H) gene mutation status and telomere length, since significantly shorter telomeres were demonstrated in the unmutated group compared to the mutated group (mean length 4.3 vs 6.3 kbp). Shorter telomeres also constituted a subgroup with a worse prognosis than cases with longer telomeres (median survival 59 vs 159 months). Furthermore, the Ig gene sequence data revealed that samples with high mutations frequency (>6%) had long telomeres ( approximately 8 kbp). Thus, both the telomere and V(H) gene mutation status in CLL appear linked, which may reflect the proliferative history of the clonal cells with regard to the GC reaction.

Aged↗
PubMed2003

Increased serum levels of interleukin-9 correlate to negative prognostic factors in Hodgkin's lymphoma.

Hodgkin's lymphoma (HL) is characterised by an unbalanced cytokine secretion. Many of these cytokines have been implicated in the regulation of malignant and infiltrating cells. Interleukin-9 (IL-9) has been described to act in an autocrine fashion in HL, stimulating proliferation of the malignant cells. To investigate the potential clinical implication of this observation, a novel ELISA method was used to examine the serum levels of IL-9 in lymphoma patients. High levels of IL-9 were found in the sera from patients with HL (18/44), but not in the sera from non-Hodgkin's lymphoma patients (3/21) or healthy controls. The highest serum IL-9 levels, up to 3350 pg/ml, were observed in the nodular sclerosis subtype, and there was a correlation between IL-9 levels and the negative prognostic factors advanced stage, B-symptoms, low blood Hb and high erythrocyte sedimentation rate. Furthermore, there was no correlation between serum levels of IL-9 and IL-13, a cytokine where serum levels have been speculated to be of clinical importance. This is the first report showing that IL-9 can be measured in serum samples. A novel correlation between increased serum IL-9 levels, HL and clinical features is shown, suggesting that IL-9 is a candidate factor contributing to the development of HL.

Biomarkers, Tumor↗
PubMed2001

Mast cells express functional CD30 ligand and are the predominant CD30L-positive cells in Hodgkin's disease.

Hodgkin's disease (HD) tumours are characterized by the presence of few tumour cells, the Hodgkin and Reed-Sternberg (HRS) cells, surrounded by a large amount of non-neoplastic cells. The role of this cell infiltrate for the development of HD is not known. CD30, belonging to the tumour necrosis factor receptor superfamily, is highly expressed on HRS cells and believed to be involved in tumourigenesis and tumour progression. Tumour samples from 42 patients were immunohistochemically double-stained for tryptase, a mast cell-specific proteinase and CD30 ligand (CD30L). Tryptase-positive mast cells were present in all tumours. Of these cells, 50% expressed CD30L and 66% of the CD30L-positive cells were mast cells. CD30L mRNA in in vitro developed normal mast cells and malignant human and murine mast cell lines was detected using reverse transcription polymerase chain reaction. CD30L protein expressed on human mast cells was detected using flow cytometry. In a co-culture assay, the human mast cell line HMC-1 stimulated thymidine uptake in HRS cell lines, and the stimulation could be blocked using CD30L-specific monoclonal antibodies. In conclusion, mast cells are present in HD tumours and are the predominant CD30L-expressing cells. CD30L-CD30 interaction is a pathway by which mast cells may stimulate DNA synthesis in HRS cells.

Adult↗
PubMed2001

The serum levels of eosinophil cationic protein (ECP) are related to the infiltration of eosinophils in the tumours of patients with Hodgkin's disease.

We have previously described a relation between abundance of eosinophilic granulocytes in Hodgkin's disease (HD) tumours and poor prognosis. In order to further explore the importance of the eosinophilic infiltration, we immunohistochemically examined the presence of eosinophils, using the monoclonal antibodies EG 1 and EG 2, in the tumours of 54 newly diagnosed patients with HD and related the degree of infiltration to clinical characteristics and the serum levels of eosinophil cationic protein (S-ECP). S-ECP levels (upper normal value 16 micrograms/l) varied between 2.2 and 71.7 micrograms/l, mean 25.4 micrograms/l. There was an association (p = 0.01) between the number of eosinophils in the tumour tissue and S-ECP. S-ECP levels were also associated to high erythrocyte sedimentation rate (ESR, p < 0.01) and nodular sclerosis (NS) histology (p < 0.05), and there was a tendency of a correlation to bulky disease (p = 0.06). The number of eosinophils stained with EG 2 correlated to high ESR (p < 0.05), and to high leukocyte count (p = 0.02). A follow-up value of S-ECP after treatment was, in most of the cases measured, lower than the initial value. The high values of S-ECP in several patients with HD probably originates from eosinophils infiltrating the tumours. The same patients had a higher ESR and tended to have a more advanced stage and bulky disease. There are no significant correlations with disease-free and overall survival, as the follow-up time is short, and prognosis favourable.

Adolescent↗
PubMed2000

Value of transsternal core biopsy in patients with a newly diagnosed mediastinal mass.

Histopathologic analysis of an anterior mediastinal mass of unknown origin is essential for treatment decision. Mediastinoscopy is the most common procedure performed to obtain biopsies, but general anaesthesia and hospitalization are necessary. The aim of this study was to evaluate whether transsternal core biopsies, an easy outpatient biopsy technique, could be an alternative to mediastinoscopy. A biopsy instrument that makes it possible to reach tumours hidden behind bone was used for transsternal CT-guided core biopsies in 21 patients with a newly diagnosed anterior mediastinal mass. No severe side effects were observed. In 19/21 (90%) patients the biopsies were diagnostic. In 2/21 patients additional biopsy techniques had to be used. In these two patients Hodgkin's disease was suspected in the first biopsy procedures. The diagnosis was confirmed by new core biopsies, from other parts of the tumour, not using a transsternal approach (transclavicular and parasternal, respectively). In addition, one mediastinoscopy was performed in a patient who was diagnosed with a non-Hodgkin's lymphoma but where more material was needed for lymphoma subclassification. It is concluded that CT-guided transsternal core biopsy is a clinically valuable method in patients with a newly diagnosed anterior mediastinal mass.

Adolescent↗
PubMed2000

Recovering DNA and optimizing PCR conditions from microdissected formalin-fixed and paraffin-embedded materials.

Microdissection is a powerful technique in molecular pathology and genetic investigations. To detect genetic alterations such as gene mutation or deletion from tumor specimen, the purity of target cells is extremely critical. Unwanted cell contamination will dramatically dilute the detectable level of the abnormality. The major obstacle in clinical research is to obtain sufficient and qualified DNA from a small amount of formalin-fixed and paraffin-embedded materials. We have successfully modified our previous protocols and overcome the difficulties of recovery of DNA. After these modifications, almost every single formalin-fixed and paraffin-embedded specimen has been successfully amplified in the required DNA region.

DNA↗
PubMed2000

Atypical lymphocytes in B-cell chronic lymphocytic leukemia and trisomy 12 studied by conventional staining combined with fluorescence in situ hybridization.

Trisomy 12 is one of the most frequent chromosomal abnormalities in B-cell chronic lymphocytic leukemia (CLL), and is predominantly found in CLL with atypical morphology (aCLL). It has been suggested that the atypical morphology might be a feature of the abnormal trisomy 12 clone, but so far it has been difficult to allocate chromosomal aberrations to individual leukemic cells identified by cytomorphology. We therefore wanted to use our MGG/FISH method, which combines fluorescence in situ hybridization (FISH) and standard cytomorphology, to study if the trisomy 12 clone in CLL was restricted to lymphocytes with atypical morphology. Peripheral blood specimens of four patients with aCLL were studied using a DNA probe against the pericentromeric region of chromosome 12. Trisomy 12 was found in 10-34 % of the lymphocytes. In three patients, the proportion of atypical and typical lymphocytes with trisomy 12 was quite comparable, and so was the percentage of atypical cells with lymphoplasmacytoid morphology and those with cleaved nucleus showing trisomy 12. Only one patient differed, since we found an overrepresentation of trisomy 12 among the atypical lymphocytes. However, this could be fully explained by the diluting effect of contaminating T-cells after chemotherapy. The results of the present study show that despite the strong association of trisomy 12 and atypical morphology in CLL, this chromosomal abnormality is not confined to lymphocytes with atypical morphology, but is also found in typical CLL cells. This supports that both cell types have the same clonal origin and that different cell morphology cannot be explained alone by the acquisition of an additional chromosome 12.

Aged↗
PubMed2000

Paraffin section storage and immunohistochemistry. Effects of time, temperature, fixation, and retrieval protocol with emphasis on p53 protein and MIB1 antigen.

It has been observed that immunoreactivity in paraffin sections decreased during storage. In this study, stored paraffin sections from both biopsy material and cultured cells were assessed for changes in immunoreactivity, using color-based image analysis to quantitate extent and intensity of the stainings. For seven of the 11 antibodies studied, storage at 20 degrees C for 16 weeks reduced the extent of immunostaining compared with that of freshly cut sections. Furthermore, increased storage temperatures resulted in a progressive loss of immunoreactivity. After 2 weeks of storage, at both 4 degrees C and 20 degrees C, p53 protein- and MIB1-antigen expression was significantly reduced regarding extent and intensity. The extent of the immunoreactivity reduced more for p53 protein than for MIB1 antigen, but the intensity did not. Boric acid was used for antigen retrieval on sections stored for 12 weeks at 20 degrees C. For both p53 protein and MIB1 antigen, this resulted in an extent and intensity of immunostaining equal to or higher than (MIB1) that obtained in freshly cut sections, using citrate buffer. Staining of cultured cells confirmed the results from biopsy material on the influence of storage temperature. Fixation time only marginally influenced the storage-related decrease in immunoreactivity. In conclusion, storage of paraffin sections leads to a varying degree of decreased immunoreactivity for several antibodies. The degree is at least partly dependent on storage time and temperature but not fixation time. However, this may be compensated for by optimizing the antigen retrieval protocol.

Antigens, Nuclear↗
PubMed1999

CHOP versus MACOP-B in aggressive lymphoma--a Nordic Lymphoma Group randomised trial.

BACKGROUND: The long-term survival of patients with advanced stage aggressive lymphoma has not improved significantly during the last twenty years. In a randomised trial, the efficacy of MACOP-B, a six-drug weekly chemotherapy regimen, was compared to CHOP, the current standard regimen, in terms of overall and failure-free survival, toxicity and health related quality of life. PATIENTS AND METHODS: Four hundred five patients with aggressive lymphoma, stage II-IV, age 18-67, were randomised to receive either 12 weeks of MACOP-B or 8 courses of CHOP over 24 weeks. Special emphasis was put in the definition of Ann Arbor stage in extranodal disease. A subset of 95 patients also entered a quality of life study, based on the EORTC QLQ-C30. RESULTS: Thirty-one patients were ineligible. Among the remaining 374 patients, the median age was 52 years. According to the age-adjusted International Prognostic Index, 37% were 'high-intermediate' or 'high-risk' patients. No difference could be demonstrated, either in overall survival (60% at five years in the MACOP-B group and 59% in the CHOP group) or in failure-free survival (47% at five years with MACOP-B and 44% with CHOP). In terms of quality of life, physical function and global quality of life were more impaired in patients receiving MACOP-B, who also exhibited more non-haematological toxicity. CONCLUSION: No superiority of MACOP-B compared to CHOP could be demonstrated. CHOP remains the treatment of choice in low-risk patients. At present, intensified or experimental treatment should be reserved for high-risk disease.

Adolescent↗
PubMed1999

The potential of human mast cell progenitors to differentiate into mature mast cells remains after prolonged culture with flt3 ligand, interleukin-3 or granulocyte-macrophage colony stimulating factor.

Stem cell factor (SCF) plays a key role in the development of mast cells from haemopoietic progenitor cells. In this study we have investigated the effect of the early acting haemopoietic cytokines flt3 ligand (FL), IL-3 and GM-CSF on the SCF-dependent differentiation of mast cells from cord blood mononuclear cells. By using delayed addition of SCF, we examined the potential of mast cell progenitors to keep their capacity to differentiate into mast cells after exposure to factors signalling differentiation into other lineages. Culture with either cytokine for 3 weeks before transfer to SCF-containing medium resulted in the development of mast cells in all cultures. The appearance of mast cells was attenuated when the cells had been in culture with IL-3 or GM-CSF prior to culture in SCF, compared to cultures exposed to SCF alone for 7 weeks. However, a proportion of the cells had not lost the capacity to develop into mast cells. In contrast, in cultures initiated with FL and transferred to medium containing SCF, the same amount of mast cells developed as in the SCF cultures. Thus, cells committed to the mast cell lineage appear to be resistant to the lineage directives of IL-3 and GM-CSF and keep their potential to differentiate into mature mast cells.

Adjuvants, Immunologic↗
PubMed1999

Linear reduction of clonal cells in stem cell enriched grafts in transplanted multiple myeloma.

In 30 patients with multiple myeloma who were scheduled for peripheral blood stem-cell transplantation, a quantitative analysis of the stem cells following enrichment by anti-CD34 was carried out. To detect the cells of the specific myeloma clone, polymerase chain reaction (PCR) was performed using unique allele-specific oligo primers for the immunoglobulin heavy chain rearrangement. The clonogenic cells before and after stem-cell enrichment, were quantified by a limiting dilution assay and a highly sensitive semi-nested PCR combined with a real-time quantitative PCR. In order to accomplish a statistically adequate end-point analysis, a large number of PCR analyses (40 per sample) were performed. By this technique the lowest detection limit observed was one myeloma cell per 106 cells. Myeloma cells were detected in 29/30 samples from the CD34-enriched fraction. The CD34 selection procedure resulted in a median 28-fold enrichment of CD34+ haemopoietic precursor cells. The stem-cell selection reduced the median concentration of clonal cells per million total cells by half, with a highly significant linear relationship between the number of myeloma cells before and after stem cell enrichment. The median depletion of clonal cells by the overall procedure was 2.15 log units, corresponding to a reduction of the total quantity of clonal cells reinfused into the patients by at least 99.3%. We conclude that CD34+ cell enrichment led to a reliable tumour cell depletion of the order of 2 log, which may not be sufficient since the total number of tumour cells in the leukapheresis product was 7.2 log (median).

Adolescent↗
PubMed1999

Epstein-Barr virus distribution in Hodgkin's disease in an unselected Swedish population.

All patients with Hodgkin's disease (HD) (n = 117) identified in the Uppsala/Orebro region of Sweden between 1985 and 1988 were examined for the presence of Epstein-Barr virus (EBV) in the Hodgkin and Reed-Sternberg (HRS) cells. EBV was detected with LMP-1 immunostaining and in situ hybridization for EBERs. Overall, 32 (27%) tumours were EBV-positive but there were significant differences in EBV-positivity between histopathological subgroups (p = 0.03). In MC, 8/21 (38%) were positive, in NS 20/67 (23%), LD 3/3, LP 1/5, and in unclassified 0/1. Patients with EBV-positive tumours were significantly older, mean 52 vs. 42 years (p = 0.02), and were likely to have significantly more B-symptoms or advanced stage disease. Patients with EBV-positive tumours tended to have a poorer survival rate (p = 0.11). The proportion of EBV-positive tumours, and especially the proportion of EBV-positive MC, was lower than previously reported. This could be explained by selection of patients from previous studies, or by differences in EBV-positivity in different geographical or ethnic populations of HD.

Adolescent↗